Novel Coronavirus COVID-19

“If anything kills over 10 million people in the next few decades, it’s most likely to be a highly infectious virus, rather than a war. Not missiles, but microbes. Now, part of this reason is that we’ve invested a huge amount in nuclear deterrents, but we’ve actually invested very little in a system to stop an epidemic. We’re not ready for the next epidemic.” —Bill Gates, TEDx, Vancouver, British Columbia, Canada, 2015 The outbreak of a novel coronavirus, referred to as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or coronavirus disease-19 (COVID-19), with its sentinel case in Wuhan, People’s Republic of China, in December 2019, has spread rapidly beyond the People’s Republic of China. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a worldwide pandemic, at which time >118,000 people across 114 countries, territories, and areas had been infected by this virus1. COVID-19 has rapidly become a global public health threat, endangering the health and well-being of all people, but especially vulnerable populations2,3. The pandemic has also precipitated social disruption, exceptional health-care utilization, and economic instability worldwide. Controlling the spread of COVID-19 has become the singular focus of several countries, with unprecedented international collaboration and rapid dissemination of emerging scientific evidence. Table I summarizes what we know about COVID-19. TABLE I - COVID-19: What We Know Topic Key Facts What is COVID-19? Coronavirus originating from Wuhan, People’s Republic of China, in December 2019 Originated from an animal source How is it transmitted? Can be transmitted directly (via droplets through sneezing or coughing) or indirectly (via contaminated surfaces) Can be transmitted by asymptomatic and pre-symptomatic persons Every infected person can be expected to spread disease to approximately 2 more people Global pandemic Global pandemic declared March 11, 2020 As of March 23, 2020: 332,930 infected and 14,510 dead Clinical presentation and diagnosis Most common symptoms are fever and cough Symptoms present, on average, 5.1 days after infection, with 97.5% of patients presenting by 11.5 days 88.2% have abnormalities on chest radiograph Diagnosed using real-time RT-PCR Survival, serious illness, hospitalization Mortality rate estimates are approximately 4.4% in confirmed cases Comorbidities most likely linked to mortality are cardiovascular disease and diabetes 20% of cases are severe or critical Risk mitigation Good hygiene (hand washing), social distancing, and isolation are the most recommended mitigation measures Public and private closures are recommended in specific cases Race for a vaccine At least 4 Phase-I trials evaluating a vaccine have been initiated Lessons from history Social distancing seems effective in flattening the curve from evidence of the 1918 influenza pandemic A second wave was seen in both the SARS and 1918 influenza epidemics following relaxation of containment methods Managing expectations Pandemic expected to last well into 2020 Guiding surgeons Assess the need of planned elective or nonemergency surgical procedures Shift surgical procedures to outpatient settings, when possible Minimize the use of essential items Plan for potential surge of critical care patients Create multiple teams that are completely insulated from each another Assess the possibility of virtually or remotely completing mandatory meetings or patient examinations Implement specific infection control protocols when a surgical procedure for a patient with suspected or confirmed COVID-19 is necessary Resources U.S. CDC, WHO Evidence Review We performed a search of electronic databases (PubMed, Embase, Google Scholar) for relevant research articles on March 16, 2020. We accessed the medRxiv database for any unpublished papers, as research in this field is quickly emerging. We also searched the World Health Organization (WHO), the U.S. Centers for Disease Control and Prevention (CDC), and other government health agency websites for relevant information. What Is COVID-19? COVID-19 is the disease caused by the SARS-CoV-2 virus, which belongs to the family of coronaviruses4. Coronaviruses are positive-sense, single-stranded ribonucleic acid (RNA) viruses that infect a variety of mammalian hosts, causing a range of symptoms that primarily affect the respiratory and gastrointestinal systems5. Coronaviruses tend to cause mild symptoms in humans, although several strains, including the viruses responsible for the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks, have been linked to more severe symptoms and mortality6. SARS-CoV-2 was isolated from several patients in Wuhan, People’s Republic of China, and was identified as a novel coronavirus hitherto unknown to the medical field7. The virus was named from its phylogenetic and taxonomic similarities to the SARS coronavirus (SARS-CoV), the cause of the SARS outbreak in 2002 to 20034. SARS-CoV-2 represents the seventh known coronavirus. How Does COVID-19 Spread? The transmission characteristics of SARS-CoV-2 were originally unclear, but it soon became apparent that the virus originated from an unknown animal source and was now spreading from human to human8. The major route of transmission is through direct routes, such as respiratory droplets produced through coughing or sneezing, between people who are in close contact with one another, and through contact with contaminated surfaces or objects9. Although much of the focus has been on isolating symptomatic patients, there has been some potential evidence of transmission in asymptomatic patients (i.e., patients who are infected but not exhibiting symptoms associated with COVID-19)10–12. At the time of this writing, growing evidence suggests that asymptomatic, pre-symptomatic, or mildly symptomatic individuals could be drivers of the community spread of the virus. Some recent reports on asymptomatic cases have suggested that viral shedding can last close to a month9,13, although it is unclear how great the risk of transmission might be throughout this period. Emerging mathematical models analyzing the outbreaks in Singapore and Tianjin, People’s Republic of China, also support the existence of asymptomatic and pre-symptomatic transmission of COVID-1914. Researchers analyzing the outbreak data from Tianjin and Singapore found that infection was transmitted, on average, 2.55 days prior to symptom onset in Tianjin and 2.89 days prior to symptom onset in Singapore in each cluster14. Several studies have sought to establish the basic reproductive number (R0) for SARS-CoV-2. The R0 represents the number of new cases that can be expected to stem from each unique case. An early examination of the first 425 patients in Wuhan found that the R0 was 2.2 (95% confidence interval CI, 1.4 to 3.9), meaning that each person infected with COVID-19 can be expected to infect at least 2 other people15. Another analysis looking at the outbreak on the Diamond Princess cruise ship found a similar estimate (R0, 2.28 95% CI, 2.06 to 2.52)16. For Italy, Remuzzi and Remuzzi estimated that this was between 2.76 to 3.2517. COVID-19 follows other recent coronavirus outbreaks, including the SARS outbreak of 2002 to 2003 and the MERS outbreak of 2012. The SARS outbreak saw >8,000 confirmed cases from 26 countries, of which 774 cases (9.6%) were fatal5. Since 2012, there have been 2,494 laboratory-confirmed cases of MERS in 27 countries, with 858 cases (34.4%) being fatal18. Global Pandemic By definition19, “a pandemic is the worldwide spread of a new disease.” It can be transmitted between people and spread worldwide because of the absence of preexisting immunity against the new virus in humans19. The 2009 H1N1 swine flu pandemic infected about 700 million to 1.4 billion people and caused 150,000 to 575,000 deaths20. The epicenter of the outbreak emerged in a series of cases of pneumonia with unknown cause in Wuhan City, Hubei Province, People’s Republic of China, in December 201921. From December 31, 2019, to January 3, 2020, the WHO received notice of 44 new cases of pneumonia of unknown origin from the People’s Republic of China21. The first countries outside of the People’s Republic of China to report cases were Japan, South Korea, and Thailand22. The WHO declared a pandemic on March 11, 2020. Within 5 days of this declaration, the virus had resulted in 167,511 cases in >140 countries and territories, with 6,606 deaths23. Figure 1 illustrates a timeline of important events associated with COVID-19. Chinese laboratories successfully isolated a new type of coronavirus, after conducting tests on all suspected cases on January 7, 202024. From the middle to late January 2020, Thailand, Japan, South Korea, and the United States reported their first cases of confirmed COVID-1921,25. By the end of January 2020, 9,826 confirmed cases were identified globally across 20 countries26.Fig. 1: Timeline of important COVID-19 events.On the second meeting of the International Health Regulations Emergency Committee on January 30, 2020, the WHO declared a Public Health Emergency of International Concern (PHEIC)27. The term PHEIC is defined as27: “an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease; and to potentially require a coordinated international response.” Also, according to the WHO28, “This definition implies a situation that is serious, unusual, or unexpected; carries implications for public health beyond the affected state’s national border; and may require immediate international action.” Eleven days later, on February 10, 2020, there were, cumulatively, 40,554 confirmed cases and 910 deaths globally across 25 countries, and the majority were identified in the People’s Republic of China29. On February 11, 2020, the WHO announced a name for the new coronavirus disease: COVID-1930. Since then, the numbers of confirmed cases and deaths have been escalating globally. By March 10, 2020, there were >110,000 cases and >4,000 deaths across 110 countries31. One day later, on March 11, 2020, in to the the WHO announced COVID-19 to be a pandemic on >118,000 cases in 114 countries and deaths to the The 5 countries with the to are the People’s Republic of China, Italy, South Korea, and Clinical and The of the the between and the of the first symptoms of infection, for COVID-19 is The evidence from an analysis of confirmed COVID-19 cases from and countries outside of Hubei between January 2020, and February 2020, estimated the to be 5.1 days (95% CI, to all infected estimate that of cases symptoms 2.2 days (95% CI, to of and that 97.5% of cases symptoms 11.5 days (95% CI, to real-time is the for of the SARS-CoV-2 virus in respiratory procedures with and and of COVID-19 have that the of infection with SARS-CoV-2 to be with a range including asymptomatic infection, mild respiratory illness, severe viral pneumonia with respiratory and Table a of common symptoms patients with COVID-19 from an unpublished of studies including a of patients who were for The found although fever was the most common symptom in patients, patients had fever as their onset that of patients had abnormalities on a chest with or with a was in of patients, and of patients had of TABLE - Clinical Symptoms in with COVID-19 symptoms or symptoms sneezing, are as the number of patients, with the in Survival, and of the rapid case the of asymptomatic and and its across patient the estimates of the mortality risk have been On average, at the time of this writing, the WHO reported that the time between symptom onset and from 2 to As of March 23, 2020, the WHO reported a mortality estimate of 4.4% in confirmed cases the rate was in at suggested that a more estimate of mortality not be to the number of confirmed cases patients are infected much but be on the number of patients who were infected at the time as who the risk of mortality on this using data as of March 2020, the number of deaths in 1 day by the number of confirmed cases days analysis to mortality of (95% CI, to for the People’s Republic of China and (95% CI, to outside of the People’s Republic of this estimate was (95% CI, to a similar analysis on patients in Wuhan, the estimate was when not the of infection, that the risk of mortality can be some that this risk is actually because of the number of and suggested that reported estimates are as asymptomatic cases have not been in the risk of with and the of a analysis that deaths in the People’s Republic of China, the Coronavirus Emergency found that were patients of when this range to who were of this number to of in this the found that the mortality rate in patients with was about it was in patients with cardiovascular in patients with in patients with respiratory and in patients with in a report by the estimated that the risk of in was and the was in with cardiovascular disease diabetes respiratory disease or of confirmed cases are with mild to disease and about of cases severe disease and other respiratory and the of cases are critical cases or multiple similar to the risk of patients who are of and with preexisting are at the risk of severe a on COVID-19 patients in People’s Republic of China, patients who were as severe or cases and found that patients with severe cases were of with for patients with and were more likely to have with Several reports have suggested that the time from symptom onset to care is approximately 10 a recent found that of patients were to the the by confirmed cases in Wuhan, were to the because of respiratory that or an by on patients, the rate was with and a on patients in China, were to the and when looking at patients with severe that of cases and Although the evidence that patients and with health are at of severe disease and individuals be about severe infected with COVID-19. The a report on U.S. patients with using data from February 2020, to March 16, 2020, although their rate may be (i.e., patients in the had of both and care and for reported COVID-19 by in the United States from February 2020, to March 16, 2020. patients with coronavirus disease 2019 United February 16, 2020. March 2020. to specific or not constitute its or by the U.S. of Health and or Centers for Disease Control and at the agency the of patients in the the time from onset to who for mild cases was about 2 this was between and for who had severe or critical The of severe disease was about 1 from onset and deaths at 2 to Risk As the number of cases to rapidly across the there is growing that health-care quickly become and to to the The number of cases in at as of March 23, medical and hospitalization has the health-care some are to and there are a of and a of medical such as for patients with more serious and the spread that individuals require medical at any time are referred to as the of the or measures to the rate of infection, the number of people who COVID-19 over a of time likely with a on health-care health-care and about which patients and which patients a curve the or number of cases but over a of A rate of infection the on health-care and patients to A major by and health-care is the apparent evidence that the virus can be spread by asymptomatic and pre-symptomatic evidence from studies of 2 that the virus is on average, 2 to days symptoms As there is vaccine that can against infection, the spread of the virus, in patients a through and public health have and control on of of transmission of the virus TABLE - in all hygiene for symptomatic individuals and of individuals symptoms of health on global closures and other measures Public closures and other measures Public health isolation to community spread of COVID-19. March 2020. World Health 2020. hygiene the and coughing or sneezing into a or and of for symptomatic Social distancing to close contact between people to COVID-19 transmission in the of measures but are not to events and or to from and public such as to community countries have their to all outside of the as well as or international to the spread from countries with cases of COVID-19 to the an isolation from other individuals by a of 2 in the United is who not have symptoms but may have been to the virus through close contact with with COVID-19 or who have outside their are recommended to for The is to the time for symptoms to present, as studies have found that the presentation of symptoms by by isolating for a person with symptoms and be to be not spreading the virus in the community the period. Race for a The for a COVID-19 vaccine has become the focus of several research teams globally as to and a vaccine that can potentially cases of the disease in in Canada, the People’s Republic of China, and the United States are all at of vaccine with human trials likely by the time of this At least 4 Phase-I trials are on including in the United States and the People’s Republic of China One of the from at the of a SARS coronavirus vaccine is the for other to an in or the of and are all SARS-CoV-2 vaccine the with to following and the associated with virus be are for TABLE - on China China China United States Another potential vaccine is which on an against the to its with the 2 A number of including the of and of have all a or SARS-CoV-2 the potential for and the similarities between and SARS-CoV-2 acid the potential for a vaccine may be the most in the The is a acid for which several major have there has not been a successfully human acid although in animal studies have although there has been and rapid a vaccine a vaccine that is ready for use is likely the and that need to be The for a vaccine but not be on to for a of containment in the measures at viral spread be the public health for the Clinical specific is recommended for COVID-19. to other viral the of early and with symptomatic and for the of care including critical care on the of including pneumonia or acute respiratory syndrome The use of and is not recommended when specific are but million and have all been as potentially and may be in severe A of with care with COVID-19. patients were patients with and was between the 2 in of time to or with more events in the evidence on in this but it has been to SARS-CoV-2 in in with At least 2 are evaluating the of in COVID-19 and has been found to SARS-CoV-2 in and a number of trials are to its Although are early have been much that the from the of and of in the People’s Republic of China has recommended for patients with mild to severe COVID-19 who not have any from patients is also being on with coronavirus there is a of evidence for in and there is a risk of events as well as of the which can patients at a potentially risk for or other Lessons from The and As we are now human coronavirus of the with 1 in each the of H1N1 and the 1918 influenza known as the may into what may be expected One of the common seen in both outbreaks was the of multiple epidemics in the late and early at which the relevant and public health to to the viral the case of the 1918 influenza pandemic, the of the first wave were between and there were very few deaths from the the second which was by the of the between and have been for the and of this second including transmission and in the although the A wave in early The 1918 influenza pandemic also an of the and of the of social distancing A the public health of and the pandemic, in which public health measures such as social distancing in a rapid and and some measures after the of the first the first case being reported on a was in days The in between the 2 was with of and of and of and of and second of A on multiple of influenza is an the of the which and in any the and source are of social distancing from 1918 to December Public health and the 1918 influenza by The of through the the SARS which was first in late February also had a On the WHO from the SARS as there had been new cases of community spread or for 20 as to their a second of cases in middle to late most of cases were a with and cases this second We not have any the coronavirus in the is The MERS not with a second and the of the second for the 1918 influenza and SARS were very the most important that can be from outbreaks are a and for a possible second wave and a of for any new cases of respiratory in the to following a in new the can also with to the and of Table a of with their and a of the global TABLE - Pandemic Mortality as of Global of to to million to to million 1918 influenza 1918 to to million to to 5 million Managing for COVID-19 We are in the of an unprecedented pandemic, the of which we have not seen in over a Although the global has been and research to and of the of COVID-19 It is to the of COVID-19 because of its rapidly but some have to this using models are likely that containment measures are in with containment the outbreak is to for to public data from the Health of China from January 2020, to February 2020, and estimated for the majority of the People’s Republic of China, be seen in Wuhan, this is expected to to the of another by the performed a from infected cases between January 2020, and March 10, and estimated in Japan, there be a of cases by the end of March 2020 and cases by the end of 2020 and that of be infected by the end of the data be to and outbreak has of data and an to the of and The for in has with other to the COVID-19 relevant articles about COVID-19 and to such as to to new about the Guiding Pandemic The COVID-19 pandemic has to a on the health-care surgeons with as to how to this in of their and for their A number of major surgical and with direct patients with suspected or confirmed COVID-19 have or to to in and all health-care We their Assess all planned elective or nonemergency surgical procedures and to or not can be or in that it may be another to we some Shift and surgical procedures to outpatient settings, when Minimize the use of essential items Plan for the potential surge of critical care patients and have and Create multiple teams that are completely insulated from each or not to the spread of the but also to that are to health-care system to a possible in patient or to the a be and patient examinations virtually or a surgical procedure is necessary for a patient with suspected or confirmed use an with a and a spread is a it is also important to the an and have the and protocols in to the spread of infection in this in which to on and be or to the surgical items and medical and Minimize into and from the surgical time between procedures to and the to through on by the and the WHO on a COVID-19 is a global pandemic that has infected globally. and cough are the most common symptoms of the and it is important to that the virus can be transmitted by individuals who for the disease but not have any reported mortality because of the rapid spread of the disease and to this but it is that the risk of is associated with and the of Risk mitigation (i.e., social distancing, and have been across major It is essential that we as the outbreak is expected to last for more and we be of the from to a second wave from