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How to write an essay on coronavirus (COVID-19)

(Last updated: 10 November 2021)

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With the coronavirus pandemic affecting every aspect of our lives for the last 18 months, it is no surprise that it has become a common topic in academic assignments. Writing a COVID-19 essay can be challenging, whether you're studying biology, philosophy, or any course in between.

Your first question might be, how would an essay about a pandemic be any different from a typical academic essay? Well, the answer is that in many ways it is largely similar. The key difference, however, is that this pandemic is much more current than usual academic topics. That means that it may be difficult to rely on past research to demonstrate your argument! As a result, COVID-19 essay writing needs to balance theories of past scholars with very current data (that is constantly changing).

In this post, we are going to give you our top tips on how to write a coronavirus academic essay, so that you are able to approach your writing with confidence and produce a great piece of work.

1. Do background reading

Critical reading is an essential component for any essay, but the question is – what should you be reading for a coronavirus essay? It might seem like a silly question, but the choices that you make during the reading process may determine how well you actually do on the paper. Therefore, we recommend the following steps.

First, read (and re-read) the assignment prompt that you have been given by the instructor. If you write an excellent essay, but it is off topic, you’ll likely be marked down. Make notes on the words that explain what is being asked of you – perhaps the essay asks you to “analyse”, “describe”, “list”, or “evaluate”. Make sure that these same words actually appear in your paper.

Second, look for specific things you have been instructed to do. This might include using themes from your textbook or incorporating assigned readings. Make a note of these things and read them first. Remember to take good notes while you read.

Once you have done your course readings, the question then becomes: what types of external readings are you going to need? Typically, at this point, you are going to be left with newspapers/websites, and a few scholarly articles (books on coronavirus might not be readily available at this stage, but could still be useful!). If it is a research essay, you are likely going to need to rely on a variety of sources as you work through this assignment. This might seem different than other academic writing where you would typically focus on only peer-reviewed articles or books. With coronavirus essays, there is a need for a more diverse set of sources, including;

Newspaper articles and websites

Just like with academic articles, not all newspaper articles and/or websites are created equal. Further, there are likely to be a variety of different statistics released, as the way that countries calculate coronavirus cases, deaths, and other components of the virus are not always the same.

Try to pick sources that are reputable. This might be reports done by key governmental organisations or even the World Health Organisation. If you are reading through an article and can identify obvious areas of bias, you may need to find alternate readings for your paper.

Academic articles

You may be surprised to discover the variety of articles published so far on COVID-19 - a lot can be achieved over multiple lockdowns! The research that has been done has been fairly extensive, covering a broad range of topics. Therefore, when preparing to write your academic essay, make sure to check the literature frequently as new publications are being released all the time.

If you do a search and you cannot find anything on the coronavirus specifically, you will have to widen your search. Think about the topic more widely. Are there theories that you have learned about in your classes that you can link to academic articles? Surely the answer must be yes! Just because there is limited research on this topic does not mean that you should avoid academic articles all together. Relying solely on websites or newspapers can lead you to a biased piece of writing, which usually is not what an academic essay is all about.

2. Plan your essay

Brainstorming.

Taking the time to brainstorm out your ideas can be the first step in a super successful essay. Brainstorming does not have to take a lot of time, and can be done in about 20 minutes if you have already done some background reading on the topic.

First, figure out how many points you need to identify. Each point is likely to equate to one paragraph of your paper, so if you are writing a 1500-word essay (and you use 300 words for the introduction and conclusion) you will be left with 1200 words, which means you will need between 5-6 paragraphs (and 5-6 points).

Start with a blank piece of paper. In the middle of the paper write the question or statement that you are trying to answer. From there, draw 5 or 6 lines out from the centre. At the end of each of these lines will be a point you want to address in your essay. From here, write down any additional ideas that you have.

It might look messy, but that’s OK! This is just the first step in the process and an opportunity for you to get your ideas down on paper. From this messiness, you can easily start to form a logical and linear outline that will soon become the template for your essay.

Creating an outline

Once you have a completed brainstorm, the next step is to put your ideas into a logical format The first step in this process is usually to write out a rough draft of the argument you are attempting to make. In doing this, you are then able to see how your subsequent paragraphs are addressing this topic (and if they are not addressing the topic, now is the time to change this!).

Once you have a position/argument/thesis statement, create space for your body paragraphs, but numbering each section. Then, write a rough draft of the topic sentence that you think will fit well in that section. Once you have done this, pull up the coronavirus articles, data, and other reports that you have read. Determine where each will fit best in your paper (and exclude the ones that do not fit well). Put a citation of the document in each paragraph section (this will make it easier to construct your reference list at the end).

Once every paragraph is organised, double check to make sure they are all still on track to address your main thesis. At this point you are ready to write an excellent and well-organised COVID-19 essay!

3. Structure your paragraphs

When structuring an academic essay on COVID-19, there will be a need to balance the news, evidence from academic articles, and course theory. This adds an extra layer of complexity because there are just so many things to juggle.

One strategy that can be helpful is to structure all your paragraphs in the same way. Now, you might be thinking, how boring! In reality, it is likely that the reader will appreciate the fact that you have carefully thought out your process and how you are going to approach this essay.

How to design your essay paragraphs

  • Create a topic sentence. A topic sentence is a sentence that presents the main idea for the paragraph. Usually it links back to your thesis, argument, or position.
  • Start to introduce your evidence. Use the next sentence in your introduction as a bridge between the topic sentence and the evidence/data you are going to present.
  • Add evidence. Take 2-4 sentences to give the reader some good information that supports your topic sentence. This can be statistics, details from an empirical study, information from a news article, or some other form of information.
  • Give some critical thought. It is essential to make a connection for the reader between your evidence and your topic sentence. Tell the reader why the information you have presented is important.
  • Provide a concluding sentence. Make sure you wrap up your argument or transition to the next one.

4. Write your essay

Keep it academic.

There is a lot of information available about the coronavirus, but because much of it is coming from newspaper articles, the evidence that you might use for your paper can be skewed. In order to keep your paper academic, it is best to maintain a professional and academic style.

Present statistics from reputable sources (like the World Health Organisation), rather than those that have been selected by third parties. Furthermore, if you are writing a COVID-19 essay that is about a specific region (e.g. the United Kingdom), make sure that your statistics and evidence also come from this region.

Use up-to-date sources

The information on coronavirus is constantly changing. By now, everyone has seen the exponential curve of cases reoccurring all over the world at different times. Therefore, what was true last month may not necessarily be the case now. This can be challenging when you are planning an essay, because your outline from a previous week may need to be modified.

There are a number of ways you can address this. One way is, obviously, to continue going back and refreshing the data. Another way, which can be equally useful, is to outline the scope of the problem in your paper, writing something like, “data on COVID-19 is constantly changing, but the data presented was accurate at the time of writing”.

Avoid personal bias or opinion (unless asked!)

Everybody has an opinion – this opinion can often relate to how you or your family members have been affected by the pandemic (and the government response to this). People have lost jobs, have had to avoid family/friends, or have lost someone as a result of this pandemic. Life, for many, is very different.

While all of this is extremely important, it may not necessarily be relevant for an academic essay. One of the more challenging components of this type of academic paper is to try and remove yourself from the evidence you are providing. Now… there are exceptions. If you are writing a COVID-19 reflective essay, then it is your responsibility to include your opinion; otherwise, do your best to remain objective.

Avoid personal pronouns

Along the same lines as avoiding bias, it is also a good idea to avoid personal pronouns in your academic essay (except in a reflection, of course). This means avoiding words like “I, we, our, my”. While you may agree (or disagree) with the sentiment you are presenting, try and present your information from a distanced perspective.

Proofread carefully

Finally (and this is true of any essay), make sure that you take the time to proofread your essay carefully. Is it free from spelling errors? Have you checked the grammar? Have you made sure that your references are correct and in order? Have you carefully reviewed the submission requirements of your instructor (e.g. font, margins, spacing, etc.)? If the answer is yes, it sounds as if you are finally ready to submit your essay.

Final thoughts

Writing an essay is not easy. Writing an essay on a pandemic while living in that same pandemic is even more difficult.

A good essay is appropriately structured with a clear purpose and is presented according to the recommended guidelines. Unless it is a personal reflection, it attempts to present information as if it were free from bias.

So before you start to panic about having to write an essay about a pandemic, take a breath. You can do this. Take all the same steps as you would in a conventional academic essay, but expand your search to include relevant and up-to-date information that you know will make your essay a success. Once you have done this, make sure to have your university writing centre or an academic at Oxbridge Essays check it over and make suggestions! Now, stop reading and get writing! Good luck.

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Introduction - Pandemic Preparedness | Lessons From COVID-19

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  • The work ahead—home

On December 31, 2019, the World Health Organization (WHO) contacted China about media reports of a cluster of viral pneumonias in Wuhan, later attributed to a coronavirus, now named SARS-CoV-2 . By January 30, 2020, scarcely a month later, WHO declared the virus to be a public health emergency of international concern (PHEIC)—the highest alarm the organization can sound. Thirty days more and the pandemic was well underway; the coronavirus had spread to more than seventy countries and territories on six continents, and there were roughly ninety thousand confirmed cases worldwide of COVID-19, the disease caused by the coronavirus.

The COVID-19 pandemic is far from over and could yet evolve in unanticipated ways, but one of its most important lessons is already clear: preparation and early execution are essential in detecting, containing, and rapidly responding to and mitigating the spread of potentially dangerous emerging infectious diseases. The ability to marshal early action depends on nations and global institutions being prepared for the worst-case scenario of a severe pandemic and ready to execute on that preparedness The COVID-19 pandemic is far from over and could yet evolve in unanticipated ways, but one of its most important lessons is already clear: preparation and early execution are essential in detecting, containing, and rapidly responding to and mitigating the spread of potentially dangerous emerging infectious diseases. The ability to marshal early action depends on nations and global institutions being prepared for the worst-case scenario of a severe pandemic and ready to execute on that preparedness before that worst-case outcome is certain.

The rapid spread of the coronavirus and its devastating death toll and economic harm have revealed a failure of global and U.S. domestic preparedness and implementation, a lack of cooperation and coordination across nations, a breakdown of compliance with established norms and international agreements, and a patchwork of partial and mishandled responses. This pandemic has demonstrated the difficulty of responding effectively to emerging outbreaks in a context of growing geopolitical rivalry abroad and intense political partisanship at home.

Pandemic preparedness is a global public good. Infectious disease threats know no borders, and dangerous pathogens that circulate unabated anywhere are a risk everywhere. As the pandemic continues to unfold across the United States and world, the consequences of inadequate preparation and implementation are abundantly clear. Despite decades of various commissions highlighting the threat of global pandemics and international planning for their inevitability, neither the United States nor the broader international system were ready to execute those plans and respond to a severe pandemic. The result is the worst global catastrophe since World War II.

The lessons of this pandemic could go unheeded once life returns to a semblance of normalcy and COVID-19 ceases to menace nations around the globe. The United States and the world risk repeating many of the same mistakes that exacerbated this crisis, most prominently the failure to prioritize global health security, to invest in the essential domestic and international institutions and infrastructure required to achieve it, and to act quickly in executing a coherent response at both the national and the global level.

The goal of this report is to curtail that possibility by identifying what went wrong in the early national and international responses to the coronavirus pandemic and by providing a road map for the United States and the multilateral system to better prepare and execute in future waves of the current pandemic and when the next pandemic threat inevitably emerges. This report endeavors to preempt the next global health challenge before it becomes a disaster.

A Rapid Spread, a Grim Toll, and an Economic Disaster

On January 23, 2020, China’s government began to undertake drastic measures against the coronavirus, imposing a lockdown on Wuhan, a city of ten million people, aggressively testing, and forcibly rounding up potential carriers in makeshift quarantine centers. 1 In the subsequent days and weeks, the Chinese government extended containment to most of the country, sealing off cities and villages and mobilizing tens of thousands of health workers to contain and treat the disease. By the time those interventions began, however, the disease had already spread well beyond the country’s borders.

SARS-CoV-2 is a highly transmissible emerging infectious disease for which no highly effective treatments or vaccines currently exist and against which people have no preexisting immunity. Some nations have been successful so far in containing its spread through public health measures such as testing, contact tracing, and isolation of confirmed and suspected cases. Those nations have managed to keep the number of cases and deaths within their territories low.

More than one hundred countries implemented either a full or a partial shutdown in an effort to contain the spread of the virus and reduce pressure on their health systems. Although these measures to enforce physical distancing slowed the pace of infection, the societal and economic consequences in many nations have been grim. The supply chain for personal protective equipment (PPE), testing kits, and medical equipment such as oxygen treatment equipment and ventilators remains under immense pressure to meet global demand.

If international cooperation in response to COVID-19 has been occurring at the top levels of government, evidence of it has been scant, though technical areas such as data sharing have witnessed some notable successes. Countries have mostly gone their own ways, closing borders and often hoarding medical equipment. More than a dozen nations are competing in a biotechnology arms race to find a vaccine. A proposed international arrangement to ensure timely equitable access to the products of that biomedical innovation has yet to attract the necessary support from many vaccine-manufacturing nations, and many governments are now racing to cut deals with pharmaceutical firms and secure their own supplies.

As of August 31, 2020, the pandemic had infected at least twenty-five million people worldwide and killed at least 850,000 (both likely gross undercounts), including at least six million reported cases and 183,000 deaths in the United States. Meanwhile, the world economy had collapsed into a slump rivaling or surpassing the Great Depression, with unemployment rates averaging 8.4 percent in high-income economies. In the second quarter of 2020, the U.S gross domestic product (GDP) fell 9.5 percent, the largest quarterly decline in the nation’s history. 2

Already in May 2020, the Asia Development Bank estimated that the pandemic would cost the world $5.8 to 8.8 trillion, reducing global GDP in 2020 by 6.4 to 9.7 percent. The ultimate financial cost could be far higher. 3

The United States is among the countries most affected by the coronavirus, with about 24 percent of global cases (as of August 31) but just 4 percent of the world’s population. While many countries in Europe and Asia succeeded in driving down the rate of transmission in spring 2020, the United States experienced new spikes in infections in the summer because the absence of a national strategy left it to individual U.S. states to go their own way on reopening their economies. In the hardest-hit areas, U.S. hospitals with limited spare beds and intensive care unit capacity have struggled to accommodate the surge in COVID-19 patients. Resource-starved local and state public health departments have been unable to keep up with the staggering demand for case identification, contract tracing, and isolation required to contain the coronavirus’s spread.

A Failure to Heed Warnings

  • Institute of Medicine, Microbial Threats to Health (1992)
  • National Intelligence Estimate, The Global Infectious Disease Threat and Its Implications ...

This failing was not for any lack of warning of the dangers of pandemics. Indeed, many had sounded the alarm over the years. For nearly three decades, countless epidemiologists, public health specialists, intelligence community professionals, national security officials, and think tank experts have underscored the inevitability of a global pandemic of an emerging infectious disease. Starting with the Bill Clinton administration, successive administrations, including the current one, have included pandemic preparedness and response in their national security strategies. The U.S. government, foreign counterparts, and international agencies commissioned multiple scenarios and tabletop exercises that anticipated with uncanny accuracy the trajectory that a major outbreak could take, the complex national and global challenges it would create, and the glaring gaps and limitations in national and international capacity it would reveal.

The global health security community was almost uniformly in agreement that the most significant natural threat to population health and global security would be a respiratory virus—either a novel strain of influenza or a coronavirus that jumped from animals to humans. 4 Yet, for all this foresight and planning, national and international institutions alike have failed to rise to the occasion.

  • National Intelligence Estimate, The Global Infectious Disease Threat and Its Implications for the United States (2000)
  • Launch of the U.S. Global Health Security Initiative (2001)
  • Institute of Medicine, Microbial Threats to Health: Emergence, Detection, and Response (2003)
  • Revision of the International Health Regulations (2005)
  • World Health Organization, Global Influenza Preparedness Plan (2005)
  • Homeland Security Council, National Strategy for Pandemic Influenza (2005)
  • U.S. Department of Health and Human Services, National Health Security Strategy of the United States of America (2009)
  • U.S. Director of National Intelligence, Worldwide Threat Assessments (2009–2019)
  • World Health Organization, Report of Review Committee on the Functioning of the International Health Regulations (2005) in Relation to Pandemic (H1N1) 2009 (2011)
  • Pandemic and All-Hazards Preparedness Reauthorization Act of 2013
  • Launch of the Global Health Security Agenda (2014)
  • Blue Ribbon Study Panel on Biodefense (now Bipartisan Commission on Biodefense) (2015)
  • National Security Strategy (2017)
  • National Biodefense Strategy (2018)
  • Crimson Contagion Simulation (2019)
  • Global Preparedness Monitoring Board, A Work at Risk: Annual Report on Global Preparedness for Health Emergencies (2019)
  • CSIS Commission, Ending the Cycle of Crisis and Complacency in U.S. Global Health Security (2019)
  • U.S. National Health Security Strategy, 2019–2022 (2019)
  • Global Health Security Index (2019)

Further Reading

Health-Systems Strengthening in the Age of COVID-19

By Angela E. Micah , Katherine Leach-Kemon , Joseph L Dieleman August 25, 2020

What Is the World Doing to Create a COVID-19 Vaccine?

By Claire Felter Aug 26, 2020

What Does the World Health Organization Do?

By CFR.org Editors Jun 1, 2020

  • Research article
  • Open access
  • Published: 04 June 2021

Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

  • Israel Júnior Borges do Nascimento 1 , 2 ,
  • Dónal P. O’Mathúna 3 , 4 ,
  • Thilo Caspar von Groote 5 ,
  • Hebatullah Mohamed Abdulazeem 6 ,
  • Ishanka Weerasekara 7 , 8 ,
  • Ana Marusic 9 ,
  • Livia Puljak   ORCID: orcid.org/0000-0002-8467-6061 10 ,
  • Vinicius Tassoni Civile 11 ,
  • Irena Zakarija-Grkovic 9 ,
  • Tina Poklepovic Pericic 9 ,
  • Alvaro Nagib Atallah 11 ,
  • Santino Filoso 12 ,
  • Nicola Luigi Bragazzi 13 &
  • Milena Soriano Marcolino 1

On behalf of the International Network of Coronavirus Disease 2019 (InterNetCOVID-19)

BMC Infectious Diseases volume  21 , Article number:  525 ( 2021 ) Cite this article

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Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes.

Eighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as “critically low”. Identified symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%.

Conclusions

In this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

Peer Review reports

The spread of the “Severe Acute Respiratory Coronavirus 2” (SARS-CoV-2), the causal agent of COVID-19, was characterized as a pandemic by the World Health Organization (WHO) in March 2020 and has triggered an international public health emergency [ 1 ]. The numbers of confirmed cases and deaths due to COVID-19 are rapidly escalating, counting in millions [ 2 ], causing massive economic strain, and escalating healthcare and public health expenses [ 3 , 4 ].

The research community has responded by publishing an impressive number of scientific reports related to COVID-19. The world was alerted to the new disease at the beginning of 2020 [ 1 ], and by mid-March 2020, more than 2000 articles had been published on COVID-19 in scholarly journals, with 25% of them containing original data [ 5 ]. The living map of COVID-19 evidence, curated by the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), contained more than 40,000 records by February 2021 [ 6 ]. More than 100,000 records on PubMed were labeled as “SARS-CoV-2 literature, sequence, and clinical content” by February 2021 [ 7 ].

Due to publication speed, the research community has voiced concerns regarding the quality and reproducibility of evidence produced during the COVID-19 pandemic, warning of the potential damaging approach of “publish first, retract later” [ 8 ]. It appears that these concerns are not unfounded, as it has been reported that COVID-19 articles were overrepresented in the pool of retracted articles in 2020 [ 9 ]. These concerns about inadequate evidence are of major importance because they can lead to poor clinical practice and inappropriate policies [ 10 ].

Systematic reviews are a cornerstone of today’s evidence-informed decision-making. By synthesizing all relevant evidence regarding a particular topic, systematic reviews reflect the current scientific knowledge. Systematic reviews are considered to be at the highest level in the hierarchy of evidence and should be used to make informed decisions. However, with high numbers of systematic reviews of different scope and methodological quality being published, overviews of multiple systematic reviews that assess their methodological quality are essential [ 11 , 12 , 13 ]. An overview of systematic reviews helps identify and organize the literature and highlights areas of priority in decision-making.

In this overview of systematic reviews, we aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Methodology

Research question.

This overview’s primary objective was to summarize and critically appraise systematic reviews that assessed any type of primary clinical data from patients infected with SARS-CoV-2. Our research question was purposefully broad because we wanted to analyze as many systematic reviews as possible that were available early following the COVID-19 outbreak.

Study design

We conducted an overview of systematic reviews. The idea for this overview originated in a protocol for a systematic review submitted to PROSPERO (CRD42020170623), which indicated a plan to conduct an overview.

Overviews of systematic reviews use explicit and systematic methods for searching and identifying multiple systematic reviews addressing related research questions in the same field to extract and analyze evidence across important outcomes. Overviews of systematic reviews are in principle similar to systematic reviews of interventions, but the unit of analysis is a systematic review [ 14 , 15 , 16 ].

We used the overview methodology instead of other evidence synthesis methods to allow us to collate and appraise multiple systematic reviews on this topic, and to extract and analyze their results across relevant topics [ 17 ]. The overview and meta-analysis of systematic reviews allowed us to investigate the methodological quality of included studies, summarize results, and identify specific areas of available or limited evidence, thereby strengthening the current understanding of this novel disease and guiding future research [ 13 ].

A reporting guideline for overviews of reviews is currently under development, i.e., Preferred Reporting Items for Overviews of Reviews (PRIOR) [ 18 ]. As the PRIOR checklist is still not published, this study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 statement [ 19 ]. The methodology used in this review was adapted from the Cochrane Handbook for Systematic Reviews of Interventions and also followed established methodological considerations for analyzing existing systematic reviews [ 14 ].

Approval of a research ethics committee was not necessary as the study analyzed only publicly available articles.

Eligibility criteria

Systematic reviews were included if they analyzed primary data from patients infected with SARS-CoV-2 as confirmed by RT-PCR or another pre-specified diagnostic technique. Eligible reviews covered all topics related to COVID-19 including, but not limited to, those that reported clinical symptoms, diagnostic methods, therapeutic interventions, laboratory findings, or radiological results. Both full manuscripts and abbreviated versions, such as letters, were eligible.

No restrictions were imposed on the design of the primary studies included within the systematic reviews, the last search date, whether the review included meta-analyses or language. Reviews related to SARS-CoV-2 and other coronaviruses were eligible, but from those reviews, we analyzed only data related to SARS-CoV-2.

No consensus definition exists for a systematic review [ 20 ], and debates continue about the defining characteristics of a systematic review [ 21 ]. Cochrane’s guidance for overviews of reviews recommends setting pre-established criteria for making decisions around inclusion [ 14 ]. That is supported by a recent scoping review about guidance for overviews of systematic reviews [ 22 ].

Thus, for this study, we defined a systematic review as a research report which searched for primary research studies on a specific topic using an explicit search strategy, had a detailed description of the methods with explicit inclusion criteria provided, and provided a summary of the included studies either in narrative or quantitative format (such as a meta-analysis). Cochrane and non-Cochrane systematic reviews were considered eligible for inclusion, with or without meta-analysis, and regardless of the study design, language restriction and methodology of the included primary studies. To be eligible for inclusion, reviews had to be clearly analyzing data related to SARS-CoV-2 (associated or not with other viruses). We excluded narrative reviews without those characteristics as these are less likely to be replicable and are more prone to bias.

Scoping reviews and rapid reviews were eligible for inclusion in this overview if they met our pre-defined inclusion criteria noted above. We included reviews that addressed SARS-CoV-2 and other coronaviruses if they reported separate data regarding SARS-CoV-2.

Information sources

Nine databases were searched for eligible records published between December 1, 2019, and March 24, 2020: Cochrane Database of Systematic Reviews via Cochrane Library, PubMed, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Sciences, LILACS (Latin American and Caribbean Health Sciences Literature), PDQ-Evidence, WHO’s Global Research on Coronavirus Disease (COVID-19), and Epistemonikos.

The comprehensive search strategy for each database is provided in Additional file 1 and was designed and conducted in collaboration with an information specialist. All retrieved records were primarily processed in EndNote, where duplicates were removed, and records were then imported into the Covidence platform [ 23 ]. In addition to database searches, we screened reference lists of reviews included after screening records retrieved via databases.

Study selection

All searches, screening of titles and abstracts, and record selection, were performed independently by two investigators using the Covidence platform [ 23 ]. Articles deemed potentially eligible were retrieved for full-text screening carried out independently by two investigators. Discrepancies at all stages were resolved by consensus. During the screening, records published in languages other than English were translated by a native/fluent speaker.

Data collection process

We custom designed a data extraction table for this study, which was piloted by two authors independently. Data extraction was performed independently by two authors. Conflicts were resolved by consensus or by consulting a third researcher.

We extracted the following data: article identification data (authors’ name and journal of publication), search period, number of databases searched, population or settings considered, main results and outcomes observed, and number of participants. From Web of Science (Clarivate Analytics, Philadelphia, PA, USA), we extracted journal rank (quartile) and Journal Impact Factor (JIF).

We categorized the following as primary outcomes: all-cause mortality, need for and length of mechanical ventilation, length of hospitalization (in days), admission to intensive care unit (yes/no), and length of stay in the intensive care unit.

The following outcomes were categorized as exploratory: diagnostic methods used for detection of the virus, male to female ratio, clinical symptoms, pharmacological and non-pharmacological interventions, laboratory findings (full blood count, liver enzymes, C-reactive protein, d-dimer, albumin, lipid profile, serum electrolytes, blood vitamin levels, glucose levels, and any other important biomarkers), and radiological findings (using radiography, computed tomography, magnetic resonance imaging or ultrasound).

We also collected data on reporting guidelines and requirements for the publication of systematic reviews and meta-analyses from journal websites where included reviews were published.

Quality assessment in individual reviews

Two researchers independently assessed the reviews’ quality using the “A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2)”. We acknowledge that the AMSTAR 2 was created as “a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions, or both” [ 24 ]. However, since AMSTAR 2 was designed for systematic reviews of intervention trials, and we included additional types of systematic reviews, we adjusted some AMSTAR 2 ratings and reported these in Additional file 2 .

Adherence to each item was rated as follows: yes, partial yes, no, or not applicable (such as when a meta-analysis was not conducted). The overall confidence in the results of the review is rated as “critically low”, “low”, “moderate” or “high”, according to the AMSTAR 2 guidance based on seven critical domains, which are items 2, 4, 7, 9, 11, 13, 15 as defined by AMSTAR 2 authors [ 24 ]. We reported our adherence ratings for transparency of our decision with accompanying explanations, for each item, in each included review.

One of the included systematic reviews was conducted by some members of this author team [ 25 ]. This review was initially assessed independently by two authors who were not co-authors of that review to prevent the risk of bias in assessing this study.

Synthesis of results

For data synthesis, we prepared a table summarizing each systematic review. Graphs illustrating the mortality rate and clinical symptoms were created. We then prepared a narrative summary of the methods, findings, study strengths, and limitations.

For analysis of the prevalence of clinical outcomes, we extracted data on the number of events and the total number of patients to perform proportional meta-analysis using RStudio© software, with the “meta” package (version 4.9–6), using the “metaprop” function for reviews that did not perform a meta-analysis, excluding case studies because of the absence of variance. For reviews that did not perform a meta-analysis, we presented pooled results of proportions with their respective confidence intervals (95%) by the inverse variance method with a random-effects model, using the DerSimonian-Laird estimator for τ 2 . We adjusted data using Freeman-Tukey double arcosen transformation. Confidence intervals were calculated using the Clopper-Pearson method for individual studies. We created forest plots using the RStudio© software, with the “metafor” package (version 2.1–0) and “forest” function.

Managing overlapping systematic reviews

Some of the included systematic reviews that address the same or similar research questions may include the same primary studies in overviews. Including such overlapping reviews may introduce bias when outcome data from the same primary study are included in the analyses of an overview multiple times. Thus, in summaries of evidence, multiple-counting of the same outcome data will give data from some primary studies too much influence [ 14 ]. In this overview, we did not exclude overlapping systematic reviews because, according to Cochrane’s guidance, it may be appropriate to include all relevant reviews’ results if the purpose of the overview is to present and describe the current body of evidence on a topic [ 14 ]. To avoid any bias in summary estimates associated with overlapping reviews, we generated forest plots showing data from individual systematic reviews, but the results were not pooled because some primary studies were included in multiple reviews.

Our search retrieved 1063 publications, of which 175 were duplicates. Most publications were excluded after the title and abstract analysis ( n = 860). Among the 28 studies selected for full-text screening, 10 were excluded for the reasons described in Additional file 3 , and 18 were included in the final analysis (Fig. 1 ) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Reference list screening did not retrieve any additional systematic reviews.

figure 1

PRISMA flow diagram

Characteristics of included reviews

Summary features of 18 systematic reviews are presented in Table 1 . They were published in 14 different journals. Only four of these journals had specific requirements for systematic reviews (with or without meta-analysis): European Journal of Internal Medicine, Journal of Clinical Medicine, Ultrasound in Obstetrics and Gynecology, and Clinical Research in Cardiology . Two journals reported that they published only invited reviews ( Journal of Medical Virology and Clinica Chimica Acta ). Three systematic reviews in our study were published as letters; one was labeled as a scoping review and another as a rapid review (Table 2 ).

All reviews were published in English, in first quartile (Q1) journals, with JIF ranging from 1.692 to 6.062. One review was empty, meaning that its search did not identify any relevant studies; i.e., no primary studies were included [ 36 ]. The remaining 17 reviews included 269 unique studies; the majority ( N = 211; 78%) were included in only a single review included in our study (range: 1 to 12). Primary studies included in the reviews were published between December 2019 and March 18, 2020, and comprised case reports, case series, cohorts, and other observational studies. We found only one review that included randomized clinical trials [ 38 ]. In the included reviews, systematic literature searches were performed from 2019 (entire year) up to March 9, 2020. Ten systematic reviews included meta-analyses. The list of primary studies found in the included systematic reviews is shown in Additional file 4 , as well as the number of reviews in which each primary study was included.

Population and study designs

Most of the reviews analyzed data from patients with COVID-19 who developed pneumonia, acute respiratory distress syndrome (ARDS), or any other correlated complication. One review aimed to evaluate the effectiveness of using surgical masks on preventing transmission of the virus [ 36 ], one review was focused on pediatric patients [ 34 ], and one review investigated COVID-19 in pregnant women [ 37 ]. Most reviews assessed clinical symptoms, laboratory findings, or radiological results.

Systematic review findings

The summary of findings from individual reviews is shown in Table 2 . Overall, all-cause mortality ranged from 0.3 to 13.9% (Fig. 2 ).

figure 2

A meta-analysis of the prevalence of mortality

Clinical symptoms

Seven reviews described the main clinical manifestations of COVID-19 [ 26 , 28 , 29 , 34 , 35 , 39 , 41 ]. Three of them provided only a narrative discussion of symptoms [ 26 , 34 , 35 ]. In the reviews that performed a statistical analysis of the incidence of different clinical symptoms, symptoms in patients with COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%), gastrointestinal disorders, such as diarrhea, nausea or vomiting (5.0–9.0%), and others (including, in one study only: dizziness 12.1%) (Figs. 3 , 4 , 5 , 6 , 7 , 8 and 9 ). Three reviews assessed cough with and without sputum together; only one review assessed sputum production itself (28.5%).

figure 3

A meta-analysis of the prevalence of fever

figure 4

A meta-analysis of the prevalence of cough

figure 5

A meta-analysis of the prevalence of dyspnea

figure 6

A meta-analysis of the prevalence of fatigue or myalgia

figure 7

A meta-analysis of the prevalence of headache

figure 8

A meta-analysis of the prevalence of gastrointestinal disorders

figure 9

A meta-analysis of the prevalence of sore throat

Diagnostic aspects

Three reviews described methodologies, protocols, and tools used for establishing the diagnosis of COVID-19 [ 26 , 34 , 38 ]. The use of respiratory swabs (nasal or pharyngeal) or blood specimens to assess the presence of SARS-CoV-2 nucleic acid using RT-PCR assays was the most commonly used diagnostic method mentioned in the included studies. These diagnostic tests have been widely used, but their precise sensitivity and specificity remain unknown. One review included a Chinese study with clinical diagnosis with no confirmation of SARS-CoV-2 infection (patients were diagnosed with COVID-19 if they presented with at least two symptoms suggestive of COVID-19, together with laboratory and chest radiography abnormalities) [ 34 ].

Therapeutic possibilities

Pharmacological and non-pharmacological interventions (supportive therapies) used in treating patients with COVID-19 were reported in five reviews [ 25 , 27 , 34 , 35 , 38 ]. Antivirals used empirically for COVID-19 treatment were reported in seven reviews [ 25 , 27 , 34 , 35 , 37 , 38 , 41 ]; most commonly used were protease inhibitors (lopinavir, ritonavir, darunavir), nucleoside reverse transcriptase inhibitor (tenofovir), nucleotide analogs (remdesivir, galidesivir, ganciclovir), and neuraminidase inhibitors (oseltamivir). Umifenovir, a membrane fusion inhibitor, was investigated in two studies [ 25 , 35 ]. Possible supportive interventions analyzed were different types of oxygen supplementation and breathing support (invasive or non-invasive ventilation) [ 25 ]. The use of antibiotics, both empirically and to treat secondary pneumonia, was reported in six studies [ 25 , 26 , 27 , 34 , 35 , 38 ]. One review specifically assessed evidence on the efficacy and safety of the anti-malaria drug chloroquine [ 27 ]. It identified 23 ongoing trials investigating the potential of chloroquine as a therapeutic option for COVID-19, but no verifiable clinical outcomes data. The use of mesenchymal stem cells, antifungals, and glucocorticoids were described in four reviews [ 25 , 34 , 35 , 38 ].

Laboratory and radiological findings

Of the 18 reviews included in this overview, eight analyzed laboratory parameters in patients with COVID-19 [ 25 , 29 , 30 , 32 , 33 , 34 , 35 , 39 ]; elevated C-reactive protein levels, associated with lymphocytopenia, elevated lactate dehydrogenase, as well as slightly elevated aspartate and alanine aminotransferase (AST, ALT) were commonly described in those eight reviews. Lippi et al. assessed cardiac troponin I (cTnI) [ 25 ], procalcitonin [ 32 ], and platelet count [ 33 ] in COVID-19 patients. Elevated levels of procalcitonin [ 32 ] and cTnI [ 30 ] were more likely to be associated with a severe disease course (requiring intensive care unit admission and intubation). Furthermore, thrombocytopenia was frequently observed in patients with complicated COVID-19 infections [ 33 ].

Chest imaging (chest radiography and/or computed tomography) features were assessed in six reviews, all of which described a frequent pattern of local or bilateral multilobar ground-glass opacity [ 25 , 34 , 35 , 39 , 40 , 41 ]. Those six reviews showed that septal thickening, bronchiectasis, pleural and cardiac effusions, halo signs, and pneumothorax were observed in patients suffering from COVID-19.

Quality of evidence in individual systematic reviews

Table 3 shows the detailed results of the quality assessment of 18 systematic reviews, including the assessment of individual items and summary assessment. A detailed explanation for each decision in each review is available in Additional file 5 .

Using AMSTAR 2 criteria, confidence in the results of all 18 reviews was rated as “critically low” (Table 3 ). Common methodological drawbacks were: omission of prospective protocol submission or publication; use of inappropriate search strategy: lack of independent and dual literature screening and data-extraction (or methodology unclear); absence of an explanation for heterogeneity among the studies included; lack of reasons for study exclusion (or rationale unclear).

Risk of bias assessment, based on a reported methodological tool, and quality of evidence appraisal, in line with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method, were reported only in one review [ 25 ]. Five reviews presented a table summarizing bias, using various risk of bias tools [ 25 , 29 , 39 , 40 , 41 ]. One review analyzed “study quality” [ 37 ]. One review mentioned the risk of bias assessment in the methodology but did not provide any related analysis [ 28 ].

This overview of systematic reviews analyzed the first 18 systematic reviews published after the onset of the COVID-19 pandemic, up to March 24, 2020, with primary studies involving more than 60,000 patients. Using AMSTAR-2, we judged that our confidence in all those reviews was “critically low”. Ten reviews included meta-analyses. The reviews presented data on clinical manifestations, laboratory and radiological findings, and interventions. We found no systematic reviews on the utility of diagnostic tests.

Symptoms were reported in seven reviews; most of the patients had a fever, cough, dyspnea, myalgia or muscle fatigue, and gastrointestinal disorders such as diarrhea, nausea, or vomiting. Olfactory dysfunction (anosmia or dysosmia) has been described in patients infected with COVID-19 [ 43 ]; however, this was not reported in any of the reviews included in this overview. During the SARS outbreak in 2002, there were reports of impairment of the sense of smell associated with the disease [ 44 , 45 ].

The reported mortality rates ranged from 0.3 to 14% in the included reviews. Mortality estimates are influenced by the transmissibility rate (basic reproduction number), availability of diagnostic tools, notification policies, asymptomatic presentations of the disease, resources for disease prevention and control, and treatment facilities; variability in the mortality rate fits the pattern of emerging infectious diseases [ 46 ]. Furthermore, the reported cases did not consider asymptomatic cases, mild cases where individuals have not sought medical treatment, and the fact that many countries had limited access to diagnostic tests or have implemented testing policies later than the others. Considering the lack of reviews assessing diagnostic testing (sensitivity, specificity, and predictive values of RT-PCT or immunoglobulin tests), and the preponderance of studies that assessed only symptomatic individuals, considerable imprecision around the calculated mortality rates existed in the early stage of the COVID-19 pandemic.

Few reviews included treatment data. Those reviews described studies considered to be at a very low level of evidence: usually small, retrospective studies with very heterogeneous populations. Seven reviews analyzed laboratory parameters; those reviews could have been useful for clinicians who attend patients suspected of COVID-19 in emergency services worldwide, such as assessing which patients need to be reassessed more frequently.

All systematic reviews scored poorly on the AMSTAR 2 critical appraisal tool for systematic reviews. Most of the original studies included in the reviews were case series and case reports, impacting the quality of evidence. Such evidence has major implications for clinical practice and the use of these reviews in evidence-based practice and policy. Clinicians, patients, and policymakers can only have the highest confidence in systematic review findings if high-quality systematic review methodologies are employed. The urgent need for information during a pandemic does not justify poor quality reporting.

We acknowledge that there are numerous challenges associated with analyzing COVID-19 data during a pandemic [ 47 ]. High-quality evidence syntheses are needed for decision-making, but each type of evidence syntheses is associated with its inherent challenges.

The creation of classic systematic reviews requires considerable time and effort; with massive research output, they quickly become outdated, and preparing updated versions also requires considerable time. A recent study showed that updates of non-Cochrane systematic reviews are published a median of 5 years after the publication of the previous version [ 48 ].

Authors may register a review and then abandon it [ 49 ], but the existence of a public record that is not updated may lead other authors to believe that the review is still ongoing. A quarter of Cochrane review protocols remains unpublished as completed systematic reviews 8 years after protocol publication [ 50 ].

Rapid reviews can be used to summarize the evidence, but they involve methodological sacrifices and simplifications to produce information promptly, with inconsistent methodological approaches [ 51 ]. However, rapid reviews are justified in times of public health emergencies, and even Cochrane has resorted to publishing rapid reviews in response to the COVID-19 crisis [ 52 ]. Rapid reviews were eligible for inclusion in this overview, but only one of the 18 reviews included in this study was labeled as a rapid review.

Ideally, COVID-19 evidence would be continually summarized in a series of high-quality living systematic reviews, types of evidence synthesis defined as “ a systematic review which is continually updated, incorporating relevant new evidence as it becomes available ” [ 53 ]. However, conducting living systematic reviews requires considerable resources, calling into question the sustainability of such evidence synthesis over long periods [ 54 ].

Research reports about COVID-19 will contribute to research waste if they are poorly designed, poorly reported, or simply not necessary. In principle, systematic reviews should help reduce research waste as they usually provide recommendations for further research that is needed or may advise that sufficient evidence exists on a particular topic [ 55 ]. However, systematic reviews can also contribute to growing research waste when they are not needed, or poorly conducted and reported. Our present study clearly shows that most of the systematic reviews that were published early on in the COVID-19 pandemic could be categorized as research waste, as our confidence in their results is critically low.

Our study has some limitations. One is that for AMSTAR 2 assessment we relied on information available in publications; we did not attempt to contact study authors for clarifications or additional data. In three reviews, the methodological quality appraisal was challenging because they were published as letters, or labeled as rapid communications. As a result, various details about their review process were not included, leading to AMSTAR 2 questions being answered as “not reported”, resulting in low confidence scores. Full manuscripts might have provided additional information that could have led to higher confidence in the results. In other words, low scores could reflect incomplete reporting, not necessarily low-quality review methods. To make their review available more rapidly and more concisely, the authors may have omitted methodological details. A general issue during a crisis is that speed and completeness must be balanced. However, maintaining high standards requires proper resourcing and commitment to ensure that the users of systematic reviews can have high confidence in the results.

Furthermore, we used adjusted AMSTAR 2 scoring, as the tool was designed for critical appraisal of reviews of interventions. Some reviews may have received lower scores than actually warranted in spite of these adjustments.

Another limitation of our study may be the inclusion of multiple overlapping reviews, as some included reviews included the same primary studies. According to the Cochrane Handbook, including overlapping reviews may be appropriate when the review’s aim is “ to present and describe the current body of systematic review evidence on a topic ” [ 12 ], which was our aim. To avoid bias with summarizing evidence from overlapping reviews, we presented the forest plots without summary estimates. The forest plots serve to inform readers about the effect sizes for outcomes that were reported in each review.

Several authors from this study have contributed to one of the reviews identified [ 25 ]. To reduce the risk of any bias, two authors who did not co-author the review in question initially assessed its quality and limitations.

Finally, we note that the systematic reviews included in our overview may have had issues that our analysis did not identify because we did not analyze their primary studies to verify the accuracy of the data and information they presented. We give two examples to substantiate this possibility. Lovato et al. wrote a commentary on the review of Sun et al. [ 41 ], in which they criticized the authors’ conclusion that sore throat is rare in COVID-19 patients [ 56 ]. Lovato et al. highlighted that multiple studies included in Sun et al. did not accurately describe participants’ clinical presentations, warning that only three studies clearly reported data on sore throat [ 56 ].

In another example, Leung [ 57 ] warned about the review of Li, L.Q. et al. [ 29 ]: “ it is possible that this statistic was computed using overlapped samples, therefore some patients were double counted ”. Li et al. responded to Leung that it is uncertain whether the data overlapped, as they used data from published articles and did not have access to the original data; they also reported that they requested original data and that they plan to re-do their analyses once they receive them; they also urged readers to treat the data with caution [ 58 ]. This points to the evolving nature of evidence during a crisis.

Our study’s strength is that this overview adds to the current knowledge by providing a comprehensive summary of all the evidence synthesis about COVID-19 available early after the onset of the pandemic. This overview followed strict methodological criteria, including a comprehensive and sensitive search strategy and a standard tool for methodological appraisal of systematic reviews.

In conclusion, in this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all the reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic could be categorized as research waste. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards to provide patients, clinicians, and decision-makers trustworthy evidence.

Availability of data and materials

All data collected and analyzed within this study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank Catherine Henderson DPhil from Swanscoe Communications for pro bono medical writing and editing support. We acknowledge support from the Covidence Team, specifically Anneliese Arno. We thank the whole International Network of Coronavirus Disease 2019 (InterNetCOVID-19) for their commitment and involvement. Members of the InterNetCOVID-19 are listed in Additional file 6 . We thank Pavel Cerny and Roger Crosthwaite for guiding the team supervisor (IJBN) on human resources management.

This research received no external funding.

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University Hospital and School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

Israel Júnior Borges do Nascimento & Milena Soriano Marcolino

Medical College of Wisconsin, Milwaukee, WI, USA

Israel Júnior Borges do Nascimento

Helene Fuld Health Trust National Institute for Evidence-based Practice in Nursing and Healthcare, College of Nursing, The Ohio State University, Columbus, OH, USA

Dónal P. O’Mathúna

School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany

Thilo Caspar von Groote

Department of Sport and Health Science, Technische Universität München, Munich, Germany

Hebatullah Mohamed Abdulazeem

School of Health Sciences, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia

Ishanka Weerasekara

Department of Physiotherapy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka

Cochrane Croatia, University of Split, School of Medicine, Split, Croatia

Ana Marusic, Irena Zakarija-Grkovic & Tina Poklepovic Pericic

Center for Evidence-Based Medicine and Health Care, Catholic University of Croatia, Ilica 242, 10000, Zagreb, Croatia

Livia Puljak

Cochrane Brazil, Evidence-Based Health Program, Universidade Federal de São Paulo, São Paulo, Brazil

Vinicius Tassoni Civile & Alvaro Nagib Atallah

Yorkville University, Fredericton, New Brunswick, Canada

Santino Filoso

Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada

Nicola Luigi Bragazzi

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IJBN conceived the research idea and worked as a project coordinator. DPOM, TCVG, HMA, IW, AM, LP, VTC, IZG, TPP, ANA, SF, NLB and MSM were involved in data curation, formal analysis, investigation, methodology, and initial draft writing. All authors revised the manuscript critically for the content. The author(s) read and approved the final manuscript.

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Correspondence to Livia Puljak .

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Supplementary Information

Additional file 1: appendix 1..

Search strategies used in the study.

Additional file 2: Appendix 2.

Adjusted scoring of AMSTAR 2 used in this study for systematic reviews of studies that did not analyze interventions.

Additional file 3: Appendix 3.

List of excluded studies, with reasons.

Additional file 4: Appendix 4.

Table of overlapping studies, containing the list of primary studies included, their visual overlap in individual systematic reviews, and the number in how many reviews each primary study was included.

Additional file 5: Appendix 5.

A detailed explanation of AMSTAR scoring for each item in each review.

Additional file 6: Appendix 6.

List of members and affiliates of International Network of Coronavirus Disease 2019 (InterNetCOVID-19).

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Borges do Nascimento, I.J., O’Mathúna, D.P., von Groote, T.C. et al. Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews. BMC Infect Dis 21 , 525 (2021). https://doi.org/10.1186/s12879-021-06214-4

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Published : 04 June 2021

DOI : https://doi.org/10.1186/s12879-021-06214-4

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Coronavirus: The world has come together to flatten the curve. Can we stay united to tackle other crises?

Watching the world come together gives me hope for the future, writes mira patel, a high school junior..

Mira Patel and her sister Veda. (Courtesy of Dee Patel)

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Before the pandemic, I had often heard adults say that young people would lose the ability to connect in-person with others due to our growing dependence on technology and social media. However, this stay-at-home experience has proven to me that our elders’ worry is unnecessary. Because isolation isn’t in human nature, and no advancement in technology could replace our need to meet in person, especially when it comes to learning.

As the weather gets warmer and we approach summertime, it’s going to be more and more tempting for us teenagers to go out and do what we have always done: hang out and have fun. Even though the decision-makers are adults, everyone has a role to play and we teens can help the world move forward by continuing to self-isolate. It’s incredibly important that in the coming weeks, we respect the government’s effort to contain the spread of the coronavirus.

In the meantime, we can find creative ways to stay connected and continue to do what we love. Personally, I see many 6-feet-apart bike rides and Zoom calls in my future.

If there is anything that this pandemic has made me realize, it’s how connected we all are. At first, the infamous coronavirus seemed to be a problem in China, which is worlds away. But slowly, it steadily made its way through various countries in Europe, and inevitably reached us in America. What was once framed as a foreign virus has now hit home.

Watching the global community come together, gives me hope, as a teenager, that in the future we can use this cooperation to combat climate change and other catastrophes.

As COVID-19 continues to creep its way into each of our communities and impact the way we live and communicate, I find solace in the fact that we face what comes next together, as humanity.

When the day comes that my generation is responsible for dealing with another crisis, I hope we can use this experience to remind us that moving forward requires a joint effort.

Mira Patel is a junior at Strath Haven High School and is an education intern at the Foreign Policy Research Institute in Philadelphia. Follow her on Instagram here.  

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I Thought We’d Learned Nothing From the Pandemic. I Wasn’t Seeing the Full Picture

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M y first home had a back door that opened to a concrete patio with a giant crack down the middle. When my sister and I played, I made sure to stay on the same side of the divide as her, just in case. The 1988 film The Land Before Time was one of the first movies I ever saw, and the image of the earth splintering into pieces planted its roots in my brain. I believed that, even in my own backyard, I could easily become the tiny Triceratops separated from her family, on the other side of the chasm, as everything crumbled into chaos.

Some 30 years later, I marvel at the eerie, unexpected ways that cartoonish nightmare came to life – not just for me and my family, but for all of us. The landscape was already covered in fissures well before COVID-19 made its way across the planet, but the pandemic applied pressure, and the cracks broke wide open, separating us from each other physically and ideologically. Under the weight of the crisis, we scattered and landed on such different patches of earth we could barely see each other’s faces, even when we squinted. We disagreed viciously with each other, about how to respond, but also about what was true.

Recently, someone asked me if we’ve learned anything from the pandemic, and my first thought was a flat no. Nothing. There was a time when I thought it would be the very thing to draw us together and catapult us – as a capital “S” Society – into a kinder future. It’s surreal to remember those early days when people rallied together, sewing masks for health care workers during critical shortages and gathering on balconies in cities from Dallas to New York City to clap and sing songs like “Yellow Submarine.” It felt like a giant lightning bolt shot across the sky, and for one breath, we all saw something that had been hidden in the dark – the inherent vulnerability in being human or maybe our inescapable connectedness .

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Read More: The Family Time the Pandemic Stole

But it turns out, it was just a flash. The goodwill vanished as quickly as it appeared. A couple of years later, people feel lied to, abandoned, and all on their own. I’ve felt my own curiosity shrinking, my willingness to reach out waning , my ability to keep my hands open dwindling. I look out across the landscape and see selfishness and rage, burnt earth and so many dead bodies. Game over. We lost. And if we’ve already lost, why try?

Still, the question kept nagging me. I wondered, am I seeing the full picture? What happens when we focus not on the collective society but at one face, one story at a time? I’m not asking for a bow to minimize the suffering – a pretty flourish to put on top and make the whole thing “worth it.” Yuck. That’s not what we need. But I wondered about deep, quiet growth. The kind we feel in our bodies, relationships, homes, places of work, neighborhoods.

Like a walkie-talkie message sent to my allies on the ground, I posted a call on my Instagram. What do you see? What do you hear? What feels possible? Is there life out here? Sprouting up among the rubble? I heard human voices calling back – reports of life, personal and specific. I heard one story at a time – stories of grief and distrust, fury and disappointment. Also gratitude. Discovery. Determination.

Among the most prevalent were the stories of self-revelation. Almost as if machines were given the chance to live as humans, people described blossoming into fuller selves. They listened to their bodies’ cues, recognized their desires and comforts, tuned into their gut instincts, and honored the intuition they hadn’t realized belonged to them. Alex, a writer and fellow disabled parent, found the freedom to explore a fuller version of herself in the privacy the pandemic provided. “The way I dress, the way I love, and the way I carry myself have both shrunk and expanded,” she shared. “I don’t love myself very well with an audience.” Without the daily ritual of trying to pass as “normal” in public, Tamar, a queer mom in the Netherlands, realized she’s autistic. “I think the pandemic helped me to recognize the mask,” she wrote. “Not that unmasking is easy now. But at least I know it’s there.” In a time of widespread suffering that none of us could solve on our own, many tended to our internal wounds and misalignments, large and small, and found clarity.

Read More: A Tool for Staying Grounded in This Era of Constant Uncertainty

I wonder if this flourishing of self-awareness is at least partially responsible for the life alterations people pursued. The pandemic broke open our personal notions of work and pushed us to reevaluate things like time and money. Lucy, a disabled writer in the U.K., made the hard decision to leave her job as a journalist covering Westminster to write freelance about her beloved disability community. “This work feels important in a way nothing else has ever felt,” she wrote. “I don’t think I’d have realized this was what I should be doing without the pandemic.” And she wasn’t alone – many people changed jobs , moved, learned new skills and hobbies, became politically engaged.

Perhaps more than any other shifts, people described a significant reassessment of their relationships. They set boundaries, said no, had challenging conversations. They also reconnected, fell in love, and learned to trust. Jeanne, a quilter in Indiana, got to know relatives she wouldn’t have connected with if lockdowns hadn’t prompted weekly family Zooms. “We are all over the map as regards to our belief systems,” she emphasized, “but it is possible to love people you don’t see eye to eye with on every issue.” Anna, an anti-violence advocate in Maine, learned she could trust her new marriage: “Life was not a honeymoon. But we still chose to turn to each other with kindness and curiosity.” So many bonds forged and broken, strengthened and strained.

Instead of relying on default relationships or institutional structures, widespread recalibrations allowed for going off script and fortifying smaller communities. Mara from Idyllwild, Calif., described the tangible plan for care enacted in her town. “We started a mutual-aid group at the beginning of the pandemic,” she wrote, “and it grew so quickly before we knew it we were feeding 400 of the 4000 residents.” She didn’t pretend the conditions were ideal. In fact, she expressed immense frustration with our collective response to the pandemic. Even so, the local group rallied and continues to offer assistance to their community with help from donations and volunteers (many of whom were originally on the receiving end of support). “I’ve learned that people thrive when they feel their connection to others,” she wrote. Clare, a teacher from the U.K., voiced similar conviction as she described a giant scarf she’s woven out of ribbons, each representing a single person. The scarf is “a collection of stories, moments and wisdom we are sharing with each other,” she wrote. It now stretches well over 1,000 feet.

A few hours into reading the comments, I lay back on my bed, phone held against my chest. The room was quiet, but my internal world was lighting up with firefly flickers. What felt different? Surely part of it was receiving personal accounts of deep-rooted growth. And also, there was something to the mere act of asking and listening. Maybe it connected me to humans before battle cries. Maybe it was the chance to be in conversation with others who were also trying to understand – what is happening to us? Underneath it all, an undeniable thread remained; I saw people peering into the mess and narrating their findings onto the shared frequency. Every comment was like a flare into the sky. I’m here! And if the sky is full of flares, we aren’t alone.

I recognized my own pandemic discoveries – some minor, others massive. Like washing off thick eyeliner and mascara every night is more effort than it’s worth; I can transform the mundane into the magical with a bedsheet, a movie projector, and twinkle lights; my paralyzed body can mother an infant in ways I’d never seen modeled for me. I remembered disappointing, bewildering conversations within my own family of origin and our imperfect attempts to remain close while also seeing things so differently. I realized that every time I get the weekly invite to my virtual “Find the Mumsies” call, with a tiny group of moms living hundreds of miles apart, I’m being welcomed into a pocket of unexpected community. Even though we’ve never been in one room all together, I’ve felt an uncommon kind of solace in their now-familiar faces.

Hope is a slippery thing. I desperately want to hold onto it, but everywhere I look there are real, weighty reasons to despair. The pandemic marks a stretch on the timeline that tangles with a teetering democracy, a deteriorating planet , the loss of human rights that once felt unshakable . When the world is falling apart Land Before Time style, it can feel trite, sniffing out the beauty – useless, firing off flares to anyone looking for signs of life. But, while I’m under no delusions that if we just keep trudging forward we’ll find our own oasis of waterfalls and grassy meadows glistening in the sunshine beneath a heavenly chorus, I wonder if trivializing small acts of beauty, connection, and hope actually cuts us off from resources essential to our survival. The group of abandoned dinosaurs were keeping each other alive and making each other laugh well before they made it to their fantasy ending.

Read More: How Ice Cream Became My Own Personal Act of Resistance

After the monarch butterfly went on the endangered-species list, my friend and fellow writer Hannah Soyer sent me wildflower seeds to plant in my yard. A simple act of big hope – that I will actually plant them, that they will grow, that a monarch butterfly will receive nourishment from whatever blossoms are able to push their way through the dirt. There are so many ways that could fail. But maybe the outcome wasn’t exactly the point. Maybe hope is the dogged insistence – the stubborn defiance – to continue cultivating moments of beauty regardless. There is value in the planting apart from the harvest.

I can’t point out a single collective lesson from the pandemic. It’s hard to see any great “we.” Still, I see the faces in my moms’ group, making pancakes for their kids and popping on between strings of meetings while we try to figure out how to raise these small people in this chaotic world. I think of my friends on Instagram tending to the selves they discovered when no one was watching and the scarf of ribbons stretching the length of more than three football fields. I remember my family of three, holding hands on the way up the ramp to the library. These bits of growth and rings of support might not be loud or right on the surface, but that’s not the same thing as nothing. If we only cared about the bottom-line defeats or sweeping successes of the big picture, we’d never plant flowers at all.

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Impact of COVID-19 on people's livelihoods, their health and our food systems

Joint statement by ilo, fao, ifad and who.

The COVID-19 pandemic has led to a dramatic loss of human life worldwide and presents an unprecedented challenge to public health, food systems and the world of work. The economic and social disruption caused by the pandemic is devastating: tens of millions of people are at risk of falling into extreme poverty, while the number of undernourished people, currently estimated at nearly 690 million, could increase by up to 132 million by the end of the year.

Millions of enterprises face an existential threat. Nearly half of the world’s 3.3 billion global workforce are at risk of losing their livelihoods. Informal economy workers are particularly vulnerable because the majority lack social protection and access to quality health care and have lost access to productive assets. Without the means to earn an income during lockdowns, many are unable to feed themselves and their families. For most, no income means no food, or, at best, less food and less nutritious food. 

The pandemic has been affecting the entire food system and has laid bare its fragility. Border closures, trade restrictions and confinement measures have been preventing farmers from accessing markets, including for buying inputs and selling their produce, and agricultural workers from harvesting crops, thus disrupting domestic and international food supply chains and reducing access to healthy, safe and diverse diets. The pandemic has decimated jobs and placed millions of livelihoods at risk. As breadwinners lose jobs, fall ill and die, the food security and nutrition of millions of women and men are under threat, with those in low-income countries, particularly the most marginalized populations, which include small-scale farmers and indigenous peoples, being hardest hit.

Millions of agricultural workers – waged and self-employed – while feeding the world, regularly face high levels of working poverty, malnutrition and poor health, and suffer from a lack of safety and labour protection as well as other types of abuse. With low and irregular incomes and a lack of social support, many of them are spurred to continue working, often in unsafe conditions, thus exposing themselves and their families to additional risks. Further, when experiencing income losses, they may resort to negative coping strategies, such as distress sale of assets, predatory loans or child labour. Migrant agricultural workers are particularly vulnerable, because they face risks in their transport, working and living conditions and struggle to access support measures put in place by governments. Guaranteeing the safety and health of all agri-food workers – from primary producers to those involved in food processing, transport and retail, including street food vendors – as well as better incomes and protection, will be critical to saving lives and protecting public health, people’s livelihoods and food security.

In the COVID-19 crisis food security, public health, and employment and labour issues, in particular workers’ health and safety, converge. Adhering to workplace safety and health practices and ensuring access to decent work and the protection of labour rights in all industries will be crucial in addressing the human dimension of the crisis. Immediate and purposeful action to save lives and livelihoods should include extending social protection towards universal health coverage and income support for those most affected. These include workers in the informal economy and in poorly protected and low-paid jobs, including youth, older workers, and migrants. Particular attention must be paid to the situation of women, who are over-represented in low-paid jobs and care roles. Different forms of support are key, including cash transfers, child allowances and healthy school meals, shelter and food relief initiatives, support for employment retention and recovery, and financial relief for businesses, including micro, small and medium-sized enterprises. In designing and implementing such measures it is essential that governments work closely with employers and workers.

Countries dealing with existing humanitarian crises or emergencies are particularly exposed to the effects of COVID-19. Responding swiftly to the pandemic, while ensuring that humanitarian and recovery assistance reaches those most in need, is critical.

Now is the time for global solidarity and support, especially with the most vulnerable in our societies, particularly in the emerging and developing world. Only together can we overcome the intertwined health and social and economic impacts of the pandemic and prevent its escalation into a protracted humanitarian and food security catastrophe, with the potential loss of already achieved development gains.

We must recognize this opportunity to build back better, as noted in the Policy Brief issued by the United Nations Secretary-General. We are committed to pooling our expertise and experience to support countries in their crisis response measures and efforts to achieve the Sustainable Development Goals. We need to develop long-term sustainable strategies to address the challenges facing the health and agri-food sectors. Priority should be given to addressing underlying food security and malnutrition challenges, tackling rural poverty, in particular through more and better jobs in the rural economy, extending social protection to all, facilitating safe migration pathways and promoting the formalization of the informal economy.

We must rethink the future of our environment and tackle climate change and environmental degradation with ambition and urgency. Only then can we protect the health, livelihoods, food security and nutrition of all people, and ensure that our ‘new normal’ is a better one.

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How to Write About the Impact of the Coronavirus in a College Essay

The global impact of COVID-19, the disease caused by the novel coronavirus, means colleges and prospective students alike are in for an admissions cycle like no other. Both face unprecedented challenges and questions as they grapple with their respective futures amid the ongoing fallout of the pandemic.

Colleges must examine applicants without the aid of standardized test scores for many -- a factor that prompted many schools to go test-optional for now . Even grades, a significant component of a college application, may be hard to interpret with some high schools adopting pass-fail classes last spring due to the pandemic. Major college admissions factors are suddenly skewed.

"I can't help but think other (admissions) factors are going to matter more," says Ethan Sawyer, founder of the College Essay Guy, a website that offers free and paid essay-writing resources.

College essays and letters of recommendation , Sawyer says, are likely to carry more weight than ever in this admissions cycle. And many essays will likely focus on how the pandemic shaped students' lives throughout an often tumultuous 2020.

[ Read: How to Write a College Essay. ]

But before writing a college essay focused on the coronavirus, students should explore whether it's the best topic for them.

Writing About COVID-19 for a College Application

Much of daily life has been colored by the coronavirus. Virtual learning is the norm at many colleges and high schools, many extracurriculars have vanished and social lives have stalled for students complying with measures to stop the spread of COVID-19.

"For some young people, the pandemic took away what they envisioned as their senior year," says Robert Alexander, dean of admissions, financial aid and enrollment management at the University of Rochester in New York. "Maybe that's a spot on a varsity athletic team or the lead role in the fall play. And it's OK for them to mourn what should have been and what they feel like they lost, but more important is how are they making the most of the opportunities they do have?"

That question, Alexander says, is what colleges want answered if students choose to address COVID-19 in their college essay.

But the question of whether a student should write about the coronavirus is tricky. The answer depends largely on the student.

"In general, I don't think students should write about COVID-19 in their main personal statement for their application," Robin Miller, master college admissions counselor at IvyWise, a college counseling company, wrote in an email.

"Certainly, there may be exceptions to this based on a student's individual experience, but since the personal essay is the main place in the application where the student can really allow their voice to be heard and share insight into who they are as an individual, there are likely many other topics they can choose to write about that are more distinctive and unique than COVID-19," Miller says.

[ Read: What Colleges Look for: 6 Ways to Stand Out. ]

Opinions among admissions experts vary on whether to write about the likely popular topic of the pandemic.

"If your essay communicates something positive, unique, and compelling about you in an interesting and eloquent way, go for it," Carolyn Pippen, principal college admissions counselor at IvyWise, wrote in an email. She adds that students shouldn't be dissuaded from writing about a topic merely because it's common, noting that "topics are bound to repeat, no matter how hard we try to avoid it."

Above all, she urges honesty.

"If your experience within the context of the pandemic has been truly unique, then write about that experience, and the standing out will take care of itself," Pippen says. "If your experience has been generally the same as most other students in your context, then trying to find a unique angle can easily cross the line into exploiting a tragedy, or at least appearing as though you have."

But focusing entirely on the pandemic can limit a student to a single story and narrow who they are in an application, Sawyer says. "There are so many wonderful possibilities for what you can say about yourself outside of your experience within the pandemic."

He notes that passions, strengths, career interests and personal identity are among the multitude of essay topic options available to applicants and encourages them to probe their values to help determine the topic that matters most to them -- and write about it.

That doesn't mean the pandemic experience has to be ignored if applicants feel the need to write about it.

Writing About Coronavirus in Main and Supplemental Essays

Students can choose to write a full-length college essay on the coronavirus or summarize their experience in a shorter form.

To help students explain how the pandemic affected them, The Common App has added an optional section to address this topic. Applicants have 250 words to describe their pandemic experience and the personal and academic impact of COVID-19.

[ Read: The Common App: Everything You Need to Know. ]

"That's not a trick question, and there's no right or wrong answer," Alexander says. Colleges want to know, he adds, how students navigated the pandemic, how they prioritized their time, what responsibilities they took on and what they learned along the way.

If students can distill all of the above information into 250 words, there's likely no need to write about it in a full-length college essay, experts say. And applicants whose lives were not heavily altered by the pandemic may even choose to skip the optional COVID-19 question.

"This space is best used to discuss hardship and/or significant challenges that the student and/or the student's family experienced as a result of COVID-19 and how they have responded to those difficulties," Miller notes. Using the section to acknowledge a lack of impact, she adds, "could be perceived as trite and lacking insight, despite the good intentions of the applicant."

To guard against this lack of awareness, Sawyer encourages students to tap someone they trust to review their writing , whether it's the 250-word Common App response or the full-length essay.

Experts tend to agree that the short-form approach to this as an essay topic works better, but there are exceptions. And if a student does have a coronavirus story that he or she feels must be told, Alexander encourages the writer to be authentic in the essay.

"My advice for an essay about COVID-19 is the same as my advice about an essay for any topic -- and that is, don't write what you think we want to read or hear," Alexander says. "Write what really changed you and that story that now is yours and yours alone to tell."

Sawyer urges students to ask themselves, "What's the sentence that only I can write?" He also encourages students to remember that the pandemic is only a chapter of their lives and not the whole book.

Miller, who cautions against writing a full-length essay on the coronavirus, says that if students choose to do so they should have a conversation with their high school counselor about whether that's the right move. And if students choose to proceed with COVID-19 as a topic, she says they need to be clear, detailed and insightful about what they learned and how they adapted along the way.

"Approaching the essay in this manner will provide important balance while demonstrating personal growth and vulnerability," Miller says.

Pippen encourages students to remember that they are in an unprecedented time for college admissions.

"It is important to keep in mind with all of these (admission) factors that no colleges have ever had to consider them this way in the selection process, if at all," Pippen says. "They have had very little time to calibrate their evaluations of different application components within their offices, let alone across institutions. This means that colleges will all be handling the admissions process a little bit differently, and their approaches may even evolve over the course of the admissions cycle."

Searching for a college? Get our complete rankings of Best Colleges.

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Coronavirus (COVID-19) and society: what matters to people in Scotland?

Findings from an open free text survey taken to understand in greater detail how the pandemic has changed Scotland.

  • This research has captured the diversity and complexity of people’s experiences.
  • People’s experiences of the pandemic and their ability to stay safe has been impacted by a range of factors, including: their geographical environment, their financial situation, profession, their living situation and if they have any physical or mental health conditions.
  • Even though the direct level of threat from COVID-19 has reduced (for some people), there is still concern about the longer term harm and disruption that COVID-19 has caused to people and communities, and worry about the threat of future waves of infection.
  • This report captures a number of specific suggestions for support. For example, support for key workers, creating safer public environments, wide-scale financial support, greater awareness around the experiences of those who are at higher risk to COVID-19 and putting in place robust processes for learning and reflection on the impact of the pandemic.
  • Public engagement in this open and unfiltered format is an essential part of making sense of people’s attitudes and behaviours within the context of their life.

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  • Iran J Med Sci
  • v.45(4); 2020 Jul

A Narrative Review of COVID-19: The New Pandemic Disease

Kiana shirani, md.

1 Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Erfan Sheikhbahaei, MD

2 Student Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Zahra Torkpour, MD

Mazyar ghadiri nejad, phd.

3 Industrial Engineering Department, Girne American University, Kyrenia, TRNC, Turkey

Bahareh Kamyab Moghadas, PhD

4 Department of Chemical Engineering, Shiraz Branch, Islamic Azad University, Shiraz, Iran

Matina Ghasemi, PhD

5 Faculty of Business and Economics, Business Department, Girne American University, Kyrenia, TRNC, Turkey

Hossein Akbari Aghdam, MD

6 Department of Orthopedic Surgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Athena Ehsani, PhD

7 Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran

Saeed Saber-Samandari, PhD

8 New Technologies Research Center, Amirkabir University of Technology, Tehran, Iran

Amirsalar Khandan, PhD

9 Department of Electrical Engineering, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran

10 0Technology Incubator Center, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran

Nearly every 100 years, humans collectively face a pandemic crisis. After the Spanish flu, now the world is in the grip of coronavirus disease 2019 (COVID-19). First detected in 2019 in the Chinese city of Wuhan, COVID-19 causes severe acute respiratory distress syndrome. Despite the initial evidence indicating a zoonotic origin, the contagion is now known to primarily spread from person to person through respiratory droplets. The precautionary measures recommended by the scientific community to halt the fast transmission of the disease failed to prevent this contagious disease from becoming a pandemic for a whole host of reasons. After an incubation period of about two days to two weeks, a spectrum of clinical manifestations can be seen in individuals afflicted by COVID-19: from an asymptomatic condition that can spread the virus in the environment, to a mild/moderate disease with cold/flu-like symptoms, to deteriorated conditions that need hospitalization and intensive care unit management, and then a fatal respiratory distress syndrome that becomes refractory to oxygenation. Several diagnostic modalities have been advocated and evaluated; however, in some cases, diagnosis is made on the clinical picture in order not to lose time. A consensus on what constitutes special treatment for COVID-19 has yet to emerge. Alongside conservative and supportive care, some potential drugs have been recommended and a considerable number of investigations are ongoing in this regard

What’s Known

  • Substantial numbers of articles on COVID-19 have been published, yet there is controversy among clinicians and confusion among the general population in this regard. Furthermore, it is unreasonable to expect physicians to read all the available literature on this subject.

What’s New

  • This article reviews high-quality articles on COVID-19 and effectively summarizes them for healthcare providers and the general population.

Introduction

A pathogen from a human-animal virus family, the coronavirus (CoV), which was identified as the main cause of respiratory tract infections, evolved to a novel and wild kind in Wuhan, a city in Hubei Province of China, and spread throughout the world, such that it created a pandemic crisis according to the World Health Organization (WHO). CoV is a large family of viruses that were first discovered in 1960. These viruses cause such diseases as common colds in humans and animals. Sometimes they attack the respiratory system, and sometimes their signs appear in the gastrointestinal tract. There have been different types of human CoV including CoV-229E, CoV-OC43, CoV-NL63, and CoV-HKU1, with the latter two having been discovered in 2004 and 2005, respectively. These types of CoV regularly cause respiratory infections in children and adults. 1 There are also other types of these viruses that are associated with more severe symptoms. The new CoV, scientifically known as “SARS-CoV-2”, causes severe acute respiratory syndrome (SARS). 2 A newer type of the virus was discovered in September 2012 in a 60-year-old man in Saudi Arabia who died of the disease; the man had traveled to Dubai a few days earlier. The second case was a 49-year-old man in Qatar who also passed away. The discovery was first confirmed at the Health Protection Agency’s Laboratory in Colindale, London. The outbreak of this CoV is known as the Middle East Respiratory Syndrome (MERS), commonly referred to as “MERS-CoV”. The virus has infected 2260 people and has killed 912, most of them in the Middle East. 3 - 5 Finally, in December 2019, for the first time in Wuhan, in Hubei Province of China, a new type of CoV was identified that caused pneumonia in humans. 6 SARS-CoV-2 has affected 5404512 people and killed more than 343514 around the world according to the WHO situation report-127 (May 26, 2020). 3 , 7 - 10 The WHO has officially termed the disease “COVID-19”, which refers to corona, the virus, the disease, the year 2019, and its etiology (SARS-CoV-2). This type of CoV had never been seen in humans before. The initial estimates showed a mortality rate ranging from between 1% and 3% in most countries to 5% in the worst-hit areas ( Figure 1 ). 9 Some Chinese researchers succeeded in determining how SARS-CoV-2 affects human cells, which could help to develop techniques of viral detection and had antiviral therapy potential. Via a process termed “cryogenic electron microscopy (cryo-EM)”, these scientists discovered that CoV enters human cells utilizing a kind of cell membrane glycoprotein: angiotensin-converting enzyme 2 (ACE2). Then, the S protein is split into two sub-units: S1 and S2. S1 keeps a receptor-binding domain (RBD); accordingly, SARS-CoV-2 can bind to the peptidase domain of ACE2 directly. It appears that S2 subsequently plays a role in cellular fusion. Chinese researchers used the cryo-EM technique to provide ACE2 when it is linked to an amino acid transporter called “B0AT1”. They also discovered how to connect SARS-CoV-2 to ACE2-B0AT1, which is another complex structure. Given that none of these molecular structures was previously known, the researchers hoped that these studies would lead to the development of an antiviral or vaccine that would help to prevent CoV. Along the way, scientists found that ACE2 has to undergo a molecular process in which it binds to another molecule to be activated. The resulting molecule can bind two SARS-CoV-2 protein molecules simultaneously. The scientists also studied different SARS-CoV-2 RBD binding methods compared with other SARS-CoV-RBDs, which showed how subtle changes in the molecular binding sequence make the coronal structure of the virus stronger.

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Object name is IJMS-45-233-g001.jpg

Most cases with SARS-CoV-2 are asymptomatic or have mild clinical pictures such as influenza and colds. This group of patients should be detected and isolated in their homes to break the transmission chain of the disease and adhere to the precautionary recommendations in order not to infect other people. The screening process will help this group and suppress the outbreak in the community. Patients with the confirmed disease who are admitted to hospitals can contaminate this environment, which should be borne in mind by healthcare providers and policymakers.

Transmission

While the first mode of the transmission of COVID-19 to humans is still unknown, a seafood market where live animals were sold was identified as a potential source at the beginning of the outbreak in the epidemiologic investigations that found some infected patients who had visited or worked in that place. The other viruses in this family, namely MERS and SARS, were both confirmed to be zoonotic viruses. Afterward, the person-to-person spread was established as the main mode of transmission and the reason for the progression of the outbreak. 11 Similar to the influenza virus, SARS-CoV-2 spreads through the population via respiratory droplets. When an infected person coughs, sneezes, or talks, the respiratory secretions, which contain the virus, enter the environment as droplets. These droplets can reach the mucous membranes of individuals directly or indirectly when they touch an infected surface or any other source; the virus, thereafter, finds its ways to the eyes, nose, or mouth as the first incubation places. 11 - 15 It has been reported that droplets cannot travel more than two meters in the air, nor can they remain in the air owing to their high density. Nonetheless, given the other hitherto unknown modes of transmission, routine airborne transmission precautions should be considered in high-risk countries and during high-risk procedures such as manual ventilation with bags and masks, endotracheal intubation, open endotracheal suctioning, bronchoscopy, cardiopulmonary resuscitation, sputum induction, lung surgery, nebulizer therapy, noninvasive positive pressure ventilation (eg, bilevel positive airway pressure and continuous positive airway pressure ), and lung autopsy. In the early stages of the disease, the chances of the spread of the virus to other persons are high because the viral load in the body may be high despite the absence of any symptoms ( Figure 2 ). 11 - 13 The person-to-person transmission rates can be different depending on the location and the infection control intervention; still, according to the latest reports, the secondary COVID-19 infection rate ranges from 1% to 5%. 13 - 23 Although the RNA of the virus has been detected in blood and stool, fecal-oral and blood-borne transmissions are not regarded as significant modes of transmission yet. 19 - 26 There have been no reports of mother-to-fetus transmission in pregnant women. 27

An external file that holds a picture, illustration, etc.
Object name is IJMS-45-233-g002.jpg

SARS-CoV-2 mode of transmission and clinical manifestations are illustrated in this figure. The potential source of this outbreak was identified to be from animals, similar to MERS and SARS, in epidemiologic studies; nonetheless, person-to-person transmission through droplets is currently the important mode. After reaching mucous membranes by direct or indirect close contact, the virus replicates in the cells and the immune system attacks the body due to its nature. Afterward, the clinical pictures appear, which are much more similar to influenza. However, different patients will have a spectrum of signs and symptoms.

Source Investigation

Recently, the appearance of SARS-CoV-2 in society shocked the healthcare system. 28 - 32 Veterinary corona virologists reported that COVID-19 was isolated from wildlife. Several studies have shown that bats are receptors of the CoV new version in 2019 with variants and changes in the environment featuring various biological characteristics. 33 - 36 The aforementioned mammals are a major source of CoV, which causes mild-to-severe respiratory illness and can even be deadly. In recent years, the virus has killed several thousands of people of all ages. 37 - 39 The mutated alternative of the virus can be transmitted to humans and cause acute respiratory distress. 40 , 41 One of the main causes of the spread of the virus is the exotic and unusual Chinese food in Wuhan: CoV is a direct result of the Chinese food cycle. The virus is found in the body of animals such as bats, 42 and snake or bat soup is a favorite Chinese food. Therefore, this sequence is replicated continuously. Almost everyone who was infected for the first time was directly in the local Wuhan market or had indirectly tried snake or bat soup in a Chinese restaurant. An investigation stated that the Malayan pangolin (Manis javanica) was a possible host for SARS-CoV-2 and recommended that it be removed from the wet market to prevent zoonotic transmissions in the future. 43 , 44

Pathogenesis

The important mechanisms of the severe pathogenesis of SARS-CoV-2 are not fully understood. Extensive lung injury in SARS-CoV-2 has been related to increased virus titers; monocyte, macrophage, and neutrophil infiltrations into the lungs; and elevated levels of pro-inflammatory cytokines and chemokines. Thus, the clinical exacerbation of SARS-CoV-2 infection may be in consequence of a combination of direct virus-induced cytopathic and immunopathological effects due to excessive cytokinesis. Changes in the cytokine/chemokine profile during SARS infection showed increased levels of circulating cytokines such as tumor necrosis factor-α (TNF-α), C–X–C motif chemokine 10 (CXCL10), interleukin (IL)-6, and IL-8 levels, in conjunction with elevated levels of serum pro-inflammatory cytokines such as IL-1, IL-6, IL-12, interferon-gamma (IFN-γ), and transforming growth factor-β (TGF-β). Nevertheless, constant stimulation by the virus creates a cytokine storm that has been related to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) in patients with COVID-19, which may ultimately lead to diminished immunity by lowering the number of CD4+ and CD8+ T cells and natural killer cells (crucial in antiviral immunity) and decreasing cytokine production and functional ability (exhaustion). It has been shown that IL-10, an inhibitory cytokine, is a major player and a potential target for therapeutic aims. 45 - 51 Severe cases of COVID-19 have respiratory distress and failure, which has been linked to the altered metabolism of heme by SARS-CoV-2. Some virus proteins can dissociate iron from porphyrins by attacking the 1-β chain of hemoglobin, which decreases the oxygen-transferring ability of hemoglobin. Research has also indicated that chloroquine and favipiravir might inhibit this process. 52

Clinical Manifestations

SARS-CoV-2, which attacks the respiratory system, has a spectrum of manifestations; nonetheless, it has three main primary symptoms after an incubation period of about two days to two weeks: fever and its associated symptoms such as malaise/fatigue/weakness; cough, which is nonproductive in most of the cases but can be productive indeed; and shortness of breath (dyspnea) due to low blood oxygenation. Although these symptoms appear in the body of the affected person over two to 14 days, patients may refer to the clinic with gastrointestinal symptoms (nausea/vomiting-diarrhea) or decreased sense of smell and/or taste. More devastatingly, however, patients may refer to the emergency room with such coagulopathies as pulmonary thromboembolism, cerebral venous thrombosis, and other related manifestations. The WHO has stated that dry throat and dry cough are other symptoms detected in the early stages of the infection. 53 , 54 The estimations of the severity of the disease are as follows: mild (no or mild pneumonia) in 81%, severe (eg, with dyspnea, hypoxia, or >50% lung involvement on imaging within 24 to 48 hours) in 14%, and critical (eg, with respiratory failure, shock, or multiorgan dysfunction) in 5%. In the early stages, the overall mortality rate was 2.3% and no deaths were observed in non-severe patients. Patients with advanced age or underlying medical comorbidities have more mortality and morbidity. 55 Although adults of middle age and older are most commonly affected by SARS-CoV-2, individuals at any age can be infected. A few studies have reported symptomatic infection in children; still, when it occurs, it has mild symptoms. The vast majority of cases have the infection with no signs and symptoms or mild clinical pictures; they are called “the asymptomatic group”. These patients do not seek medical care and if they come into close contact with others, they can spread the virus. Therefore, quarantine in their home is the best option for the population to break the transmission of the virus. It should be considered that some of these asymptomatic patients have clinical signs such as chest computed tomography scan (CT-Scan) infiltrations. Similar to bacterial pneumonia, lower respiratory signs and symptoms are the most frequent manifestations in serious cases of COVID-19, characterized by fever, cough, dyspnea, and bilateral infiltrates on chest imaging. In a study describing pneumonia in Wuhan, the most common clinical signs and symptoms at the onset of the illness were fever in 99% (although fever might not be a universal finding), fatigue in 70%, dry cough in 59%, anorexia in 40%, myalgia in 35%, dyspnea in 31%, and sputum production in 27%. Headache, sore throat, and rhinorrhea are less common, and gastrointestinal symptoms (eg, nausea and diarrhea) are relatively rare. 7 , 42 , 43 , 45 - 48 , 56 , 57 According to our clinical experience in Iran, anosmia, atypical chest pain, diarrhea, nausea/vomiting, and hemoptysis are other presenting symptoms in the clinic. It should be noted that COVID-19 has some unexplained potential complications such as secondary bacterial infections, myocarditis, central nervous system injury, cerebral edema, MODS, acute demyelinating encephalomyelitis (ADEM), kidney injury, liver injury, new-onset seizure, coagulopathy, and arrhythmias.

Laboratory data : Complete blood counts, which constitute a routine laboratory test, have shown different results in terms of the white blood cell count: from leukopenia and lymphopenia to leukocytosis, although lymphopenia appears to be the most common. Fatal cases have exhibited severe lymphopenia accompanied by an increased level of D-dimer. Liver function enzymes can be increased; however, it is not sufficient to diagnose a disease. The serum procalcitonin level is a marker of infection, especially in bacterial diseases. Patients with COVID-19 who require intensive care unit (ICU) management may have elevated procalcitonin. Increased urea and creatinine, creatinine-phosphokinase, lactate dehydrogenase, and C-reactive protein are other findings in some cases. 7 , 56 , 57

Imaging studies : Routine chest X-ray (CXR) is widely deemed the first-step management to evaluate any respiratory involvement. Although negative findings in CXR do not rule out the viral disease, patients without common findings do not have severe disease and can, consequently, be managed in the outpatient setting. 58 , 59 Another modality is chest CT-Scan. It can be ordered in suspected cases with typical symptoms at the first step, or it can be performed after the detection of any abnormalities in CXR. The most common demonstrations in CT-Scan images are ground-glass opacification, round opacities, and crazy paving with or without bilateral consolidative abnormalities (multilobar involvement) in contrast to most cases of bacterial pneumonia, which have locally limited involvement. Pleural thickening, pleural effusion, and lymphadenopathy are less common. 58 - 61 Tree-in-bud, peribronchial distribution, nodules, and cavity are not in favor of common COVID-19 findings. Although reverse transcriptase-polymerase chain reaction (RT-PCR) is used to confirm the diagnosis, it is a time-consuming procedure and has high false-negative/false-positive findings; hence, in the emergency clinical setting, CT-Scan findings can be a good approach to make the diagnosis. It is deserving of note, however, that false-positive/false-negative cases were reported by one study to be high and other differential diagnoses should be in mind in order not to miss any other cases such as acute pulmonary edema in patients with heart disease.

Suspected cases should be diagnosed as soon as possible to isolate and control the infection immediately. COVID-19 should be considered in any patient with fever and/or lower respiratory tract symptoms with any of the following risk factors in the previous 2 weeks: close contact with confirmed or suspected cases in any environment, especially at work in healthcare places without sufficient protective equipment or long-time standing in those places, and living in or traveling from well-known places where the disease is an epidemic. 61 - 66 Patients with severe lower respiratory tract disease without alternative etiologies and a clear history of exposure should be considered having COVID-19 unless confirmed otherwise. According to the Centers for Disease Control and Prevention (CDC), sending tests to check SARS-CoV-2 in suspected cases is based on physicians’ clinical judgment. Although there are some positive cases without clinical manifestations (ie, fever and/or symptoms of acute respiratory illness such as cough and dyspnea), infectious disease and control centers should take action in society to limit the exposure of such patients to other healthy individuals. The CDC prioritizes the use of the specific test for hospitalized patients, symptomatic patients who are at risk of fatal conditions (eg, age ≥65 y, chronic medical conditions, and immunocompromising conditions) and those who have exposure risks (recent travel, contact with patients with COVID-19, and healthcare workers). 61 - 66 Although treatment should be started after the confirmation of the disease, RT-PCR for highly suspected cases is a time-consuming test; accordingly, a considerable number of clinicians favor the use of a combination of clinical manifestations with imaging modalities (eg, CT-Scan findings) and their clinical judgment regarding the probability of the disease in order not to lose more time. 61 - 66

Treatment of COVID-19

There is no confirmed recommended treatment or vaccine for SARS-CoV-2; prevention is, therefore, better than treatment. Nevertheless, the high contagiousness of COVID-19, combined with the fact that some individuals fail to adhere to precautionary measures or they have significant risk factors, means that this infectious disease is inevitable in some people. Beside supportive treatments, many types of medications have been introduced. These medications come from previous experimental studies on SARS, MERS, influenza, or human immunodeficiency virus (HIV); hence, their efficacy needs further experimental and clinical approval. Patients with mild symptoms who do not have significant risk factors should be managed in their home like a self-made quarantine (in an isolated room); still, prompt hospital admission is required if patients exhibit signs of disease deterioration. 25 , 67 , 68 Isolation from other family members is an important prevention tip. Patients should wear face masks, eat healthy and warm foods similar to when struggling with influenza or colds, do the handwashing process, dispose of the contaminated materials cautiously, and disinfect suspicious surfaces with standard disinfectants. 69 Patients with severe symptoms or admission criteria should be hospitalized with other patients who have the same disease in an isolated department. When the disease is progressed, ICU care is mandatory. 25 , 67 , 68 SARS-CoV-2 attacks the respiratory system, diminishing the oxygenation process and forcing patients with low blood oxygen saturation to take extra oxygen from different modalities. Nasal cannulae, face masks with or without a reservoir, intubation in severe cases, and then extracorporeal membrane oxygenation in refractory hypoxia have been used; however, the safety and efficacy of these measures should be evaluated. As was mentioned above, impaired coagulation is one of the major complications of the disease; consequently, alongside all recommended supportive care and drugs, anticoagulants such as heparin should be administered prophylactically ( Table 1 ). Although it is said that all the clinical signs and symptoms of COVID-19 are induced by the immune system, as other research on influenza and MERS has revealed, glucocorticoids are not recommended in COVID-19 pneumonia unless other indications are present (eg, exacerbation of chronic obstructive pulmonary disease and refractory septic shock) due to the high risk of mortality and delayed viral clearance. Earlier in the national and international guidelines, nonsteroidal anti-inflammatory drugs such as naproxen were recommended on the strength of their antipyretic and anti-inflammatory components; however, the guideline has been revised recently and acetaminophen with or without codeine is currently the favored drug in patients with COVID-19. 25 , 67 , 68 According to the pathogenesis of the disease, whereby cytokine storm and immune-cell exhaustion can be seen in severe cases, selective antibodies against harmful interleukins such as IL-6 and IL-10 or other possible agents can be therapeutic for fatal complications. Tocilizumab, an IL-6 inhibitor, albeit with limited clinical efficacy, has been introduced in China’s National Health Commission treatment guideline for severe infection with profound pulmonary involvement (ie, white lung). 70 , 87

Summary of possible anti-COVID-19 drugs

Drug NameMechanism of ActionRegimenReferences
Hydroxychloroquine sulfateAntigen-presenting cell lysosomal pH modulator; toll-like receptor family inhibitor; hemozoin biocrystalization inhibitor; altering the ACE2 glycosylation, which inhibits S-protein binding and phagocytosisFirst day, 400 mg BD and then, 200 mg BD , -
Chloroquine phosphateLate endosomal and lysosomal pH enhancer, zinc ionophore (RdRP inhibitor)First day 500 mg BD and then, 250 mg BD , -
Lopinavir/RitonavirCombined protease inhibitor400 mg/100 mg BD , , , - , ,
Atazanavir/RitonavirCombined protease inhibitor300 mg/100 mg once daily ,
AtazanavirProtease inhibitor400 mg once daily ,
FavipiravirRdRP inhibitorLoading dose, 1600 mg and then, 600 mg TDS , ,
RemdesivirRdRP inhibitorFirst day, 200 mg IV daily and then, 100 mg IV daily , , - ,
RibavirinRdRP inhibitor1200 mg BD -
OseltamivirNeuraminidase inhibitors75 mg BD ,
Interferon-β-1aAntiviral cytokine22 or 44 μg 3 times/week , , ,

mg, Milligrams; BD, Every 12 hours; RdRP, RNA-dependent RNA polymerase; TDS, Every 8 hours; IV, Intravenous; IL, Interleukin; μg, Micrograms

RNA synthesis inhibitors (eg, tenofovir disoproxil fumarate and 2’-deoxy-3’-thiacytidine [3TC]), neuraminidase inhibitors (NAIs), nucleoside analogs, lopinavir/ritonavir, atazanavir, remdesivir, favipiravir, INF-β, and Chinese traditional medicine (eg, Shufeng Jiedu and Lianhuaqingwen capsules) are the major candidates for COVID-19. 26 , 70 , 85 , 88 - 96 Antiviral drugs have been investigated for various diseases, but their efficacy in the treatment of COVID-19 is under investigation and several randomized clinical trials are ongoing to release a consensus result on the treatment of this infectious disease. Moderate-to-severe SARS-CoV-2 disease needs drug therapy. Favipiravir, a previously validated drug for influenza, is a drug that has shown promising results for COVID-19 in experimental and clinical studies, but it is under further evaluation. 70 , 79 , 80 Remdesivir, which was developed for Ebola, is an antiviral drug that is under evaluation for moderate-to-severe COVID-19 owing to its promising results in in vitro investigations. 70 , 73 - 75 , 81 Remdesivir was shown to have reduced the virus titer in infected mice with MERS-CoV and improved lung tissue damage with more efficiency compared with a group treated with lopinavir/ritonavir/INF-β. 67 , 70 Another investigation studied the potential efficacy of INF-β-1 in the early stages of COVID-19 as a potential antiviral drug. 86 Although there is some hope, an evidence-based consensus requires further clinical trials. 70 , 77 A combined protease inhibitor, lopinavir/ritonavir, is used for HIV infection and has shown interesting results for SARS and MERS in in vitro studies. 73 - 75 The clinical effectiveness of lopinavir/ritonavir for SARS-CoV-2 was also reported in a case report. 70 , 71 , 74 , 76 Atazanavir, another protease inhibitor, with or without ritonavir is another possible anti-COVID-19 treatment. 77 , 78 NAIs, including oseltamivir, zanamivir, and peramivir, are recommended as antiviral treatment in influenza. 68 Oral oseltamivir was tried for COVID-19 in China and was first recommended in the Iranian guideline for COVID-19 treatment; nevertheless, because of the absence of strong evidence indicating its efficacy for SARS-CoV-2, it was eliminated from the subsequent updates of the guideline. 85 RNA-dependent RNA polymerase inhibitors with anti-hepatitis C effects such as ribavirin have shown satisfactory results against SARS-CoV-2 RNA polymerase; however, they have limited clinical approval. 82 - 84 The well-known drugs for rheumatoid arthritis, systemic lupus erythematosus, and an antimalarial drug, chloroquine 71 and hydroxychloroquine 21 are other potential drugs for moderate-to-severe COVID-19 but with limited or no clinical appraisal. Hydroxychloroquine has exhibited better safety and fewer side effects than chloroquine, which makes it the preferred choice. 70 Furthermore, the immunomodulatory effects of hydroxychloroquine can be used to control the cytokine precipitation in the late phases of SARS-CoV-2 infections. There are numerous mechanisms for the antiviral activity of hydroxychloroquine. A weak base drug, hydroxychloroquine concentrates on such intracellular sections as endosomes and lysosomes, thereby halting viral replication in the phase of fusion and uncoating. Additionally, this immunosuppressive and antiparasitic drug is capable of altering the glycosylation of ACE2 and inhibiting both S-protein binding and phagocytosis. 72 A recent multicenter study showed that regarding the risks of cardiovascular adverse effects and mortality rates, hydroxychloroquine or chloroquine with or without a macrolide (eg, azithromycin) was not beneficial for hospitalized patients, although further research is needed to end such controversies. 97

Disease Duration

It is not easy to quarantine the patients who have fully recovered because there is evidence that they are highly infectious. 81 The recovery time for confirmed cases based on the National Health Commission reports of China’s government was estimated to range between 18 and 22 days. 73 As indicated by the WHO, the healing time seems to be around two weeks for moderate infections and 3 to 6 weeks for the severe/ serious disease. 75 Pan Feng and others studied 21 confirmed cases with COVID-19 pneumonia with about 82 CT-Scan images with a mean interval of four days. Lung abnormalities on chest CT showed the highest severity approximately 10 days after the initial onset of symptoms. All patients became clear after 11 to 26 days of hospitalization. From day zero to day 26, four stages of lung CT were defined as follows: Stage 1 (first 4 days): ground-glass opacities; Stage 2 (second 4 days): crazy-paving patterns; Stage 3 (days 9–13): maximum total CT scores in the consolidations; and Stage 4 (≥14 d): steady improvements in the consolidations with a reduction in the total CT score without any crazy-paving pattern. 74 Nevertheless, there are also rare cases reported from some studies that show the recurrence of COVID-19 after negative preliminary RT-PCR results. For example, Lan and othersstudied one hospitalized and three home-quarantined patients with COVID-19 and evaluated them with RT-PCR tests of the nucleic acid. All the patients with positive RT-PCR test results had CT imaging with ground-glass opacification or mixed ground-glass opacification and consolidation with mild-to-moderate disease. After antiviral treatments, all four patients had two consecutive negative RT-PCR test results within 12 to 32 days. Five to 13 days after hospital discharge or the discontinuation of the quarantine, RT-PCR tests were repeated, and all were positive. An additional RT-PCR test was performed using a kit from a different manufacturer, and the results were also positive. Their findings propose that a minimum percentage of recovered patients may still be infection carriers. 76

Supplements for COVID-19

Since the appearance of SARS-CoV-2 in Wuhan, China, there have been reports of the unreliable and unpredictable use of mysterious therapies. Some recommendations such as the use of certain herbs and extracts including oregano oil, mulberry leaf, garlic, and black sesame may be safe as long as people do not utilize their hands for instance. 98 According to data released by the CDC, vitamin C (VitC) supplements can decrease the risk of colds in people besides preventing CoV from spreading. The aforementioned organization states that frequent consumption of VitC supplements can also decrease the duration of the cold; however, if used only after the cold has risen, its consumption does not influence the disease course. VitC also plays an important role in the body. One of the main reasons for taking VitC is to strengthen the immune system because this vitamin plays a significant part in the immune system. Firstly, VitC can increase the production of white blood cells (lymphocytes and phagocytes) in the bone marrow, which can support and protect the body against infections. Secondly, VitC helps immune cells to function better while preserving white blood cells from damaging molecules such as free oxidative radicals and ions. Thirdly, VitC is an essential part of the skin’s immune system. This vitamin is actively transported to the skin surface, where it serves as an antioxidant and helps to strengthen the skin barrier by optimizing the collagen synthesis process. Patients with pneumonia have lower levels of VitC and have been revealed to have a longer recovery time. 69 , 99 In a randomized investigation, 200 mg/d of VitC was applied to older patients and resulted in improvements in the respiratory symptoms. Another investigation reported 80% fewer mortalities in a controlled group of VitC takers. 73 However, for effective immune system improvement, VitC should be consumed alongside adequate doses of several other supplements. Although VitC plays an important role in the body, often a balanced diet and the consumption of fresh fruits and vegetables can quickly fill the blanks. While taking high amounts of VitC is less risky because it is water-soluble and its waste is eliminated in the urine, it can induce diarrhea, nausea, and abdominal spasms at higher concentrations. Too much VitC may cause calcium-oxalate kidney stones. People with genetic hemochromatosis, an iron deficiency disorder, should consult a physician before taking any VitC supplements as high levels of VitC can lead to tissue damage. Some studies have evaluated the different doses of oral or intravenous VitC for patients admitted to the hospital for COVID-19. Although they used different regimens, all of them demonstrated satisfactory results regarding the resolution of the compilations of the disease, decreased mortality, and shortened lengths of stay in the ICU and/or the hospital. 100 , 101 Immunologists have also recommended 6 000 units of vitamin A (VitA) per day for two weeks, more than twice the recommended limit for VitA, which can create a poisoning environment over time. According to the guidance of the National Institutes of Health (NIH), middle-aged men and women should take 1 and 2 mg of VitA every day, respectively. The safe upper limit of this vitamin is 6000 mg or 5000 units, and overdose can have serious outcomes such as dizziness, nausea, headache, coma, and even death. Extreme consumption of VitA throughout pregnancy can lead to birth anomalies.

Similar to VitC, vitamin D (VitD) has antioxidant, anti-inflammatory, and immune-modulatory effects in our body such as reducing pro-inflammatory cytokines and inhibiting viral replication according to experimental studies. 83 The VitD state of our body is checked through 25 (OH) VitD in the serum. VitD deficiency is pandemic around the world due to multifactorial reasons. It has been shown that VitD deficient patients are prone to SARS-CoV-2 and, accordingly, treating VitD deficiency is not without benefits. Grant and others recommended 10 000 units per day for two weeks and then 5 000 units per day as the maintenance dose to keep the level between 40 and 100 ng/mL. 102 VitD toxicity causes gastrointestinal discomfort (dyspepsia), congestion, hypercalcemia, confusion, positional disorders, dysrhythmia, and kidney dysfunction.

James Robb, 103 a researcher who detected CoV for the first time as a consultant pathologist with the National Cancer Institute of America, suggested the influence of zinc consumption. Oral zinc supplements can be dissolved in the nback of the throat. Short-term therapy with oral zinc can decrease the duration of viral colds in adults. Zinc intake is also associated with the faster resolution of nasal congestion, nasal drainage, sore throats, and coughs. Researchers 104 , 105 have warned that the consumption of more than 1 mg of zinc a day can lead to zinc poisoning and have side effects such as lowered immune function. Children and old people with zinc insufficiency in developing nations are extremely vulnerable to pneumonia and other viral infections. It has also been determined that zinc has a major role in the production and activation of T-cell lymphocytes. 106 , 107

And finally, for high-risk people or those who work in high-risk places such as healthcare providers, hydroxychloroquine has been mentioned to be effective as a prophylactic regimen ( Table 2 ). Although different doses have been investigated so far, Pourdowlat and others recommended 200 mg daily before exposure, and for the post-exposure scenario, a loading dose of 600-800 mg followed by a maintenance dose of 200 mg daily. 74

Possible prophylactic regimens against SARS-CoV-2 infection

AgentMechanism of ActionRegimenReference
VitA Antioxidant, anti-inflammatory, immune-regulatory agent6 000 IU/d for 2 weeks -
VitC1)intravenous 200 mg/kg body weight/d, divided into 4 doses for ICU-care patients 2)oral 6 g/d 3)one 10–20 g IV (max: 1.5 g/kg) -
VitD 10 000 IU/d for 2 weeks until the 25(OH)Vit D level reaches 40–60 ng/mL and then 5 000 IU/d
ZincAntioxidant, anti-inflammatory, immune-regulatory agent, intracellular signal molecule in immune cells, RdRP inhibitorMax: 1 mg/d -
Hydroxychloroquine sulfateAntigen-presenting cell lysosomal pH modulator; toll-like receptor family inhibitor; hemozoin biocrystalization inhibitor; altering the ACE2 glycosylation, which inhibits S-protein binding and phagocytosis200 mg/d

IU, International unit; mg, Milligrams; kg, Kilograms; ICU, Intensive care unit; g, Grams; IV, Intravenous; Vit, Vitamin; ng, Nanograms; mL, Milliliter

COVID-19 Kits and Deep Learning

COVID-19 has threatened public health, and its fast global spread has caught the scientific community by surprise. 108 Hence, developing a technique capable of swiftly and reliably detecting the virus in patients is vital to prevent the spreading of the virus. 109 , 110 One of the ways to diagnose this new virus is through RT-PCR, a test that has previously demonstrated its efficacy in detecting such CoV infections as MERS-CoV and SARS-CoV. Consequently, increasing the availability of RT-PCR kits is a worldwide concern. The timing of the RT-PCR test and the type of strain collected are of vital importance in the diagnosis of COVID-19. One of the characteristics of this new virus is that the serum is negative in the early stage, while respiratory specimens are positive. The level of the virus at the early stage of the illness is also high, even though the infected individual experiences mild symptoms. 111 For the management of the emerging situation of COVID-19 in Wuhan, various effective diagnostic kits were urgently made available to markets. While a few different diagnostics kits are used merely for research endeavors, only a single kit developed by the Beijing Genome Institute (BGI) called “Real-Time Fluorescent PCR” has been authenticated for clinical diagnostics. Fluorescent RT-PCR is reliable and able to offer fast results probably within a few hours (usually within two hours). Besides RT-PCR, China has successfully developed a metagenomic-sequencing kit based on combinatorial probe-anchor synthesis that can identify virus-related bacteria, allowing observation and evaluation during the transmission of the virus. Furthermore, the metagenomic-sequencing kit based on combinatorial probe-anchor synthesis is far faster than the abovementioned fluorescent RT-PCR kit. Apart from China, a Singapore-based laboratory, Veredus, developed a virus detection kit (Vere-CoV) in late January. It is a portable Lab-On-Chip used to detect MERS-CoV, SARS-CoV, and SARS-CoV-2, in a single examination. This kit works based on the VereChip™ technology, the lines of code (LOC) program incorporating two different influential molecular biological functions (microarray and PCR) precisely. Several studies have focused on SARS-CoV diagnostic testing. These papers have presented investigative approaches to the identification of the virus using molecular testing (ie, RT-PCR). Researchers probed into the use of a nested PCR technique that contains a pre-amplification step or integrating the N gene as an extra subtle molecular marker to improve on the sensitivity. 112 - 115 CT-Scan is very useful for diagnosing, evaluating, and screening infections caused by COVID-19. One recommendation for scanning the disease is to take a scan every three to five days. According to researchers, most CT-Scan images from patients with COVID-19 are bilateral or peripheral ground-glass opacification, with or without stabilization. Nowadays, because of a paucity of computerized quantification tools, only qualitative reports and sometimes inaccurate analyses of contaminated areas are drawn upon in radiology reports. A categorization system based on the deep learning approach was proposed by a study to automatically measure infected parts and their volumetric ratios in the lung. The functionality of this system was evaluated by making some comparisons between the infected portions and the manually-delineated ones on the CT-Scan images of 300 patients with COVID-19. To increase the manual drawing of training samples and the non-interference in the automated results, researchers adopted a human-based approach in collaboration with radiologists so as to segment the infected region. This approach shortens the time to about four minutes after 3-time updating. The mean Dice similarity coefficient illustrated that the automatically detected infected parts were 91.6% similar to the manually detected ones, and the average of the percentage estimated error was 0.3% for the whole lung. 116 , 117

Prevention Considerations

In the healthcare setting, any individual with the manifestations of COVID-19 (eg, fever, cough, and dyspnea) should wear a face mask, have a separate waiting area, and keep the distance of at least two meters. Symptomatic patients should be asked about recent travel or close contact with a patient in the preceding two weeks to find other possible infected patients. The CDC and WHO have announced special precautions for healthcare providers in the hospital and during different procedures. Wearing tight-fitting face masks with special filters and impermeable face shields is necessary for all of them. 11 , 18 , 65 , 66 , 76 , 118 - 124 Other people should pay attention to the CDC and WHO preventive strategies, which recommend that individuals not touch their eyes, mouth, and nose before washing or disinfecting their hands; wash their hands regularly according to the standard protocol; use effective disinfection solutions (ie, containing at least 60% ethylic alcohol) for contaminated surfaces; cover their mouth when coughing and sneezing; avoid waiting or walking in crowded areas, and observe isolation protocols in their home. Postponing elective work and decreasing non-urgent visits and traveling to areas in the grip of COVID-19 may be useful to lessen the risk of exposure. If suspected individuals with mild symptoms are managed in outpatient settings, an isolated room with minimal exposure to others should be designed. Patients and their caregivers should wear tight-fitting face masks. 11 , 18 , 65 , 66 , 76 , 118 - 124 Substantial numbers of individuals with COVID-19 are asymptomatic with potential exposure; accordingly, a screening tool should be employed to evaluate these cases. In addition to passport checks, corona checks have been incorporated into the protocols in airports and other crowded places. The use of a remote thermometer to measure body temperature leads to an increase in the number of false-negative cases. It is, thus, essential that everyone pay sufficient heed to the WHO and CDC recommendations in their daily life. Traveling is not prohibited, but it should be restricted and passengers from any country should be monitored. 11 , 18 , 65 , 66 , 76 , 118 - 124

SARS-CoV-2 is the new highly contagious CoV, which was first reported in China. While it had a zoonotic origin in the beginning, it subsequently spread throughout the world by human contact. COVID-19 has a spectrum of manifestations, which is not lethal most of the time. To diagnose this condition, physicians can avail themselves of laboratory and imaging findings besides signs and symptoms. RT-PCR is the gold standard, but it lacks sufficient sensitivity and specificity. Although there are some potential drugs for COVID-19 and some vitamins or minerals for prophylaxis, the best preventive strategies are quarantine (staying at home) and the use of personal protective equipment and disinfectants.

Acknowledgement

The authors express their gratitude toward the Supporting Organizations for Foreign Iranian Students, Islamic Azad University Isfahan (Khorasgan) Branch, and Isfahan University of Medical Sciences.

Conflict of Interest: None declared.

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