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In the 21st century, several emergent viruses have posed a global threat. Each pathogen has emphasized the value of rapid and scalable vaccine development programs. The ongoing SARS-CoV-2 pandemic has made the importance of such efforts especially clear. New biotechnological advances in vaccinology allow for recent advances that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns. During the COVID-19 pandemic, these DNA and RNA vaccines have facilitated the development and deployment of vaccines at an unprecedented pace. This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics; the genome of SARS-CoV-2 was available as early as January 2020, facilitating global efforts in the development of DNA and RNA vaccines within two weeks of the international community becoming aware of the new viral threat. Additionally, these technologies that were previously only theoretical are not only safe but also highly efficacious. Although historically a slow process, the rapid development of vaccines during the COVID-19 crisis reveals a major shift in vaccine technologies. Here, we provide historical context for the emergence of these paradigm-shifting vaccines. We describe several DNA and RNA vaccines and in terms of their efficacy, safety, and approval status. We also discuss patterns in worldwide distribution. The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last two decades in particular and suggest a new era in vaccines against emerging pathogens.

Over the past 150 years, vaccines have revolutionized the relationship between people and disease. During the COVID-19 pandemic, technologies such as mRNA vaccines have received attention due to their novelty and successes. However, more traditional vaccine development platforms have also yielded important tools in the worldwide fight against the SARS-CoV-2 virus. A variety of approaches have been used to develop COVID-19 vaccines that are now authorized for use in countries around the world. In this review, we highlight strategies that focus on the viral capsid and outwards, rather than on the nucleic acids inside. These approaches fall into two broad categories: whole-virus vaccines and subunit vaccines. Whole-virus vaccines use the virus itself, either in an inactivated or attenuated state. Subunit vaccines contain instead an isolated, immunogenic component of the virus. Here, we highlight vaccine candidates that apply these approaches against SARS-CoV-2 in different ways. In a companion manuscript, we review the more recent and novel development of nucleic-acid based vaccine technologies. We further consider the role that these COVID-19 vaccine development programs have played in prophylaxis at the global scale. Well-established vaccine technologies have proved especially important to making vaccines accessible in low- and middle-income countries. Vaccine development programs that use established platforms have been undertaken in a much wider range of countries than those using nucleic-acid-based technologies, which have been led by wealthy Western countries. Therefore, these vaccine platforms, though less novel from a biotechnological standpoint, have proven to be extremely important to the management of SARS-CoV-2.

The COVID-19 pandemic has presented many challenges that have spurred biotechnological research to address specific problems. Diagnostics is one area where biotechnology has been critical. Diagnostic tests play a vital role in managing a viral threat by facilitating the detection of infected and/or recovered individuals. From the perspective of what information is provided, these tests fall into two major categories, molecular and serological. Molecular diagnostic techniques assay whether a virus is present in a biological sample, thus making it possible to identify individuals who are currently infected. Additionally, when the immune system is exposed to a virus, it responds by producing antibodies specific to the virus. Serological tests make it possible to identify individuals who have mounted an immune response to a virus of interest and therefore facilitate the identification of individuals who have previously encountered the virus. These two categories of tests provide different perspectives valuable to understanding the spread of SARS-CoV-2. Within these categories, different biotechnological approaches offer specific advantages and disadvantages. Here we review the categories of tests developed for the detection of the SARS-CoV-2 virus or antibodies against SARS-CoV-2 and discuss the role of diagnostics in the COVID-19 pandemic., Competing Interests: Competing Interests AuthorCompeting InterestsLast ReviewedHalie M. RandoNone2021-01-20Christian BruefferEmployee and shareholder of SAGA Diagnostics AB.2020-11-11Ronan LordanNone2020-11-03Anna Ada DattoliNone2020-03-26David ManheimNone2022-03-15Jesse G. MeyerNone2022-01-06Ariel I. MundoNone2021-12-19Dimitri PerrinNone2020-11-11David MaiNone2021-01-08Nils WellhausenNone2020-11-03COVID-19 Review ConsortiumNone2021-01-16Anthony GitterFiled a patent application with the Wisconsin Alumni Research Foundation related to classifying activated T cells2020-11-10Casey S. GreeneNone2021-01-20

The COVID-19 pandemic catalyzed the rapid dissemination of papers and preprints investigating the disease and its associated virus, SARS-CoV-2. The multifaceted nature of COVID-19 demands a multidisciplinary approach, but the urgency of the crisis combined with the need for social distancing measures present unique challenges to collaborative science. We applied a massive online open publishing approach to this problem using Manubot. Through GitHub, collaborators summarized and critiqued COVID-19 literature, creating a review manuscript. Manubot automatically compiled citation information for referenced preprints, journal publications, websites, and clinical trials. Continuous integration workflows retrieved up-to-date data from online sources nightly, regenerating some of the manuscript's figures and statistics. Manubot rendered the manuscript into PDF, HTML, LaTeX, and DOCX outputs, immediately updating the version available online upon the integration of new content. Through this effort, we organized over 50 scientists from a range of backgrounds who evaluated over 1,500 sources and developed seven literature reviews. While many efforts from the computational community have focused on mining COVID-19 literature, our project illustrates the power of open publishing to organize both technical and non-technical scientists to aggregate and disseminate information in response to an evolving crisis.

Since late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. The worldwide scientific community is forging ahead to characterize a wide range of outcomes associated with SARS-CoV-2 infection; however the underlying assumptions in these studies have varied so widely that the resulting data are difficult to compareFormal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. Even the condition itself goes by three terms, most widely "Long COVID", but also "COVID-19 syndrome (PACS)" or, "post-acute sequelae of SARS-CoV-2 infection (PASC)". In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic itself. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat., Competing Interests: Declaration of Conflicts of Interest Julie A. McMurry: Cofounder, Pryzm Health; Melissa A. Haendel: co-founder Pryzm Health

After emerging in China in late 2019, the novel coronavirus SARS-CoV-2 spread worldwide and as of mid-2021 remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus , a closely related species of SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus , which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis to identify many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases, but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease., Competing Interests: Competing Interests AuthorCompeting InterestsLast ReviewedHalie M. RandoNone2021-01-20Nils WellhausenNone2020-11-03Soumita GhoshNone2020-11-09Alexandra J. LeeNone2020-11-09Anna Ada DattoliNone2020-03-26Fengling HuNone2020-04-08James Brian ByrdFunded by FastGrants to conduct a COVID-19-related clinical trial2020-11-12Diane N. RafizadehNone2020-11-11Ronan LordanNone2020-11-03Yanjun QiNone2020-07-09Yuchen SunNone2020-11-11Christian BruefferEmployee and shareholder of SAGA Diagnostics AB.2020-11-11Jeffrey M. FieldNone2020-11-12Marouen Ben GuebilaNone2021-08-02Nafisa M. JadavjiNone2020-11-11Ashwin N. SkellyNone2020-11-11Bharath RamsundarNone2020-11-11Jinhui WangNone2021-01-21Rishi Raj GoelNone2021-01-20YoSon ParkNow employed by Pfizer (subsequent to contributions to this project)2020-01-22COVID-19 Review ConsortiumNone2021-01-16Simina M. BocaCurrently an employee at AstraZeneca, Gaithersburg, MD, USA, may own stock or stock options. Work initially conducted at Georgetown University Medical Center with writing, reviewing, and editing continued while working at AstraZeneca.2021-07-01Anthony GitterFiled a patent application with the Wisconsin Alumni Research Foundation related to classifying activated T cells2020-11-10Casey S. GreeneNone2021-01-20

Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents could reduce the pandemic's devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Such products include vitamin C, vitamin D, omega 3 polyunsaturated fatty acids, probiotics, and zinc, all of which are currently under clinical investigation. In this review, we critically appraise the evidence surrounding dietary supplements and nutraceuticals for the prophylaxis and treatment of COVID-19. Overall, further study is required before evidence-based recommendations can be formulated, but nutritional status plays a significant role in patient outcomes, and these products could help alleviate deficiencies. For example, evidence indicates that vitamin D deficiency may be associated with greater incidence of infection and severity of COVID-19, suggesting that vitamin D supplementation may hold prophylactic or therapeutic value. A growing number of scientific organizations are now considering recommending vitamin D supplementation to those at high risk of COVID-19. Because research in vitamin D and other nutraceuticals and supplements is preliminary, here we evaluate the extent to which these nutraceutical and dietary supplements hold potential in the COVID-19 crisis.

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease., Competing Interests: Competing Interests AuthorCompeting InterestsLast ReviewedHalie M. RandoNone2021-01-20Adam L. MacLeanNone2021-02-23Alexandra J. LeeNone2020-11-09Ronan LordanNone2020-11-03Sandipan RayNone2020-11-11Vikas BansalNone2021-01-25Ashwin N. SkellyNone2020-11-11Elizabeth SellNone2020-11-11John J. DziakNone2020-11-11Lamonica ShinholsterNone2020-11-11Lucy D’Agostino McGowanReceived consulting fees from Acelity and Sanofi in the past five years2020-11-10Marouen Ben GuebilaNone2021-08-02Nils WellhausenNone2020-11-03Sergey KnyazevNone2020-11-11Simina M. BocaCurrently an employee at AstraZeneca, Gaithersburg, MD, USA, may own stock or stock options.2021-07-01Stephen CaponeNone2020-11-11Yanjun QiNone2020-07-09YoSon ParkYoSon Park is affiliated with Pfizer Worldwide Research. The author has no financial interests to declare and contributed as an author prior to joining Pfizer, and the work was not part of a Pfizer collaboration nor was it funded by Pfizer.2020-01-22Yuchen SunNone2020-11-11David MaiNone2021-01-08Joel D BoerckelNone2021-03-26Christian BruefferEmployee and shareholder of SAGA Diagnostics AB.2020-11-11James Brian ByrdFunded by FastGrants to conduct a COVID-19-related clinical trial2020-11-12Jeremy P. KamilTBD2021-04-30Jinhui WangNone2021-01-21Ryan VelazquezNone2020-11-10Gregory L SzetoNone2020-11-16John P. BartonNone2020-11-11Rishi Raj GoelNone2021-01-20Serghei MangulNone2020-11-11Tiago LubianaNone2020-11-11COVID-19 Review ConsortiumNone2021-01-16Anthony GitterFiled a patent application with the Wisconsin Alumni Research Foundation related to classifying activated T cells2020-11-10Casey S. GreeneNone2021-01-20