Friday, March 20, 2020

Coronavirus disease 2019 (COVID-19) (UpToDate, 2020-3-19)

INTRODUCTIONCoronaviruses are important human and animal pathogens. At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. It rapidly spread, resulting in an epidemic throughout China, followed by an increasing number of cases in other countries throughout the world. In February 2020, the World Health Organization designated the disease COVID-19, which stands for coronavirus disease 2019 [1]. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV.
Understanding of COVID-19 is evolving. Interim guidance has been issued by the World Health Organization and by the United States Centers for Disease Control and Prevention [2,3]. Links to these and other related society guidelines are found elsewhere. (See 'Society guideline links' below.)
This topic will discuss the epidemiology, clinical features, diagnosis, management, and prevention of COVID-19. Community-acquired coronaviruses, severe acute respiratory syndrome (SARS) coronavirus, and Middle East respiratory syndrome (MERS) coronavirus are discussed separately. (See "Coronaviruses" and "Severe acute respiratory syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology".)
EPIDEMIOLOGY
Geographic distribution — Globally, more than 190,000 cases of COVID-19 have been reported. Updated case counts in English can be found on the World Health Organization and European Centre for Disease Prevention and Control websites.
Since the first reports of cases from Wuhan, a city in the Hubei Province of China, at the end of 2019, more than 80,000 COVID-19 cases have been reported in China; these include all laboratory-confirmed cases as well as clinically diagnosed cases in the Hubei Province. A joint World Health Organization (WHO)-China fact-finding mission estimated that the epidemic in China peaked between late January and early February 2020 [4]. The majority of reports have been from Hubei and surrounding provinces, but numerous cases have been reported in other provinces and municipalities throughout China [5,6].
Increasing numbers of cases have also been reported in other countries across all continents except Antarctica, and the rate of new cases outside of China has outpaced the rate in China. These cases initially occurred mainly among travelers from China and those who have had contact with travelers from China [7-11]. However, ongoing local transmission has driven smaller outbreaks in some locations outside of China, including South Korea, Italy, Iran, and Japan, and infections elsewhere have been identified in travelers from those countries [12].
In the United States, clusters of COVID-19 with local transmission have been identified throughout most of the country.
Transmission — Understanding of the transmission risk is incomplete. Epidemiologic investigation in Wuhan at the beginning of the outbreak identified an initial association with a seafood market that sold live animals, where most patients had worked or visited and which was subsequently closed for disinfection [13]. However, as the outbreak progressed, person-to-person spread became the main mode of transmission.
Person-to-person spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thought to occur mainly via respiratory droplets, resembling the spread of influenza. With droplet transmission, virus released in the respiratory secretions when a person with infection coughs, sneezes, or talks can infect another person if it makes direct contact with the mucous membranes; infection can also occur if a person touches an infected surface and then touches his or her eyes, nose, or mouth. Droplets typically do not travel more than six feet (about two meters) and do not linger in the air; however, in one letter to the editor, SARS-CoV-2 remained viable in aerosols under experimental conditions for at least three hours [14]. Given the current uncertainty regarding transmission mechanisms, airborne precautions are recommended routinely in some countries and in the setting of certain high-risk procedures in others. (See 'Infection control for suspected or confirmed cases' below.)
Viral RNA levels appear to be higher soon after symptom onset compared with later in the illness [15]; this raises the possibility that transmission might be more likely in the earlier stage of infection, but additional data are needed to confirm this hypothesis.
The reported rates of transmission from an individual with symptomatic infection vary by location and infection control interventions. According to a joint WHO-China report, the rate of secondary COVID-19 ranged from 1 to 5 percent among tens of thousands of close contacts of confirmed patients in China [16]. In the United States, the symptomatic secondary attack rate was 0.45 percent among 445 close contacts of 10 confirmed patients [17].
Transmission of SARS-CoV-2 from asymptomatic individuals (or individuals within the incubation period) has also been described [18-22]. However, the extent to which this occurs remains unknown. Large-scale serologic screening may be able to provide a better sense of the scope of asymptomatic infections and inform epidemiologic analysis; several serologic tests for SARS-CoV-2 are under development [23].
SARS-CoV-2 RNA has been detected in blood and stool specimens [24,25]. Live virus has been cultured from stool in some cases [26], but according to a joint WHO-China report, fecal-oral transmission did not appear to be a significant factor in the spread of infection [16].
VIROLOGYFull-genome sequencing and phylogenic analysis indicated that the coronavirus that causes COVID-19 is a betacoronavirus in the same subgenus as the severe acute respiratory syndrome (SARS) virus (as well as several bat coronaviruses), but in a different clade. The structure of the receptor-binding gene region is very similar to that of the SARS coronavirus, and the virus has been shown to use the same receptor, the angiotensin-converting enzyme 2 (ACE2), for cell entry [27]. The Coronavirus Study Group of the International Committee on Taxonomy of Viruses has proposed that this virus be designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [28].
The Middle East respiratory syndrome (MERS) virus, another betacoronavirus, appears more distantly related [29,30]. The closest RNA sequence similarity is to two bat coronaviruses, and it appears likely that bats are the primary source; whether COVID-19 virus is transmitted directly from bats or through some other mechanism (eg, through an intermediate host) is unknown [31]. (See "Coronaviruses", section on 'Viral serotypes'.)
In a phylogenetic analysis of 103 strains of SARS-CoV-2 from China, two different types of SARS-CoV-2 were identified, designated type L (accounting for 70 percent of the strains) and type S (accounting for 30 percent) [32]. The L type predominated during the early days of the epidemic in China, but accounted for a lower proportion of strains outside of Wuhan than in Wuhan. The clinical implications of these findings are uncertain.
CLINICAL FEATURES
Incubation period — The incubation period for COVID-19 is thought to be within 14 days following exposure, with most cases occurring approximately four to five days after exposure [33-35].
In a study of 1099 patients with confirmed symptomatic COVID-19, the median incubation period was four days (interquartile range two to seven days) [34].
Using data from 181 publicly reported, confirmed cases in China with identifiable exposure, one modeling study estimated that symptoms would develop in 2.5 percent of infected individuals within 2.2 days and in 97.5 percent of infected individuals within 11.5 days [36]. The median incubation period in this study was 5.1 days.
Spectrum of illness severity — The spectrum of symptomatic infection ranges from mild to critical; most infections are not severe [35,37-42]. Specifically, in a report from the Chinese Center for Disease Control and Prevention that included approximately 44,500 confirmed infections with an estimation of disease severity [43]:
●Mild (no or mild pneumonia) was reported in 81 percent.
●Severe disease (eg, with dyspnea, hypoxia, or >50 percent lung involvement on imaging within 24 to 48 hours) was reported in 14 percent.
●Critical disease (eg, with respiratory failure, shock, or multiorgan dysfunction) was reported in 5 percent.
●The overall case fatality rate was 2.3 percent; no deaths were reported among noncritical cases.
According to a joint World Health Organization (WHO)-China fact-finding mission, the case-fatality rate ranged from 5.8 percent in Wuhan to 0.7 percent in the rest of China [16]. Most of the fatal cases have occurred in patients with advanced age or underlying medical comorbidities (including cardiovascular disease, diabetes mellitus, chronic lung disease, hypertension, and cancer) [43,44].
The proportion of severe or fatal infections may vary by location. As an example, in Italy, 12 percent of all detected COVID-19 cases and 16 percent of all hospitalized patients were admitted to the intensive care unit; the estimated case fatality rate was 5.8 percent in mid-March [45]. In contrast, the estimated case fatality rate in mid-March in South Korea was 0.9 percent [46]. This may be related to distinct demographics of infection; in Italy, the median age of patients with infection was 64 years, whereas in Korea the median age was in the 40s. (See 'Impact of age' below.)
Impact of age — Individuals of any age can acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although adults of middle age and older are most commonly affected.
In several cohorts of hospitalized patients with confirmed COVID-19, the median age ranged from 49 to 56 years [38-40]. In a report from the Chinese Center for Disease Control and Prevention that included approximately 44,500 confirmed infections, 87 percent of patients were between 30 and 79 years old [43]. Older age was also associated with increased mortality, with a case fatality rate of 8 and 15 percent among those aged 70 to 79 years and 80 years or older, respectively.
In the United States, 2449 patients diagnosed with COVID-19 between February 12 and March 16, 2020 had age, hospitalization, and intensive care unit (ICU) information available [47]; 67 percent of cases were diagnosed in those aged ≥45 years [47], and, similar to findings from China, mortality was highest among older individuals, with 80 percent of deaths occurring in those aged ≥65 years.
Symptomatic infection in children appears to be uncommon; when it occurs, it is usually mild, although severe cases have been reported [48]. In the large Chinese report described above, only 2 percent of infections were in individuals younger than 20 years old [43]. Similarly, in South Korea, only 6.3 percent of nearly 8000 infections were in those younger than 20 years old [46]. In a small study of 10 children in China, clinical illness was mild; 8 had fever, which resolved within 24 hours, 6 had cough, 4 had sore throat, 4 had evidence of focal pneumonia on CT, and none required supplemental oxygen [49]. In another study of six children aged 1 to 7 years who were hospitalized in Wuhan with COVID-19, all had fever >102.2°F/39°C and cough, four had imaging evidence of viral pneumonia, and one was admitted to the intensive care unit; all children recovered [50].
Asymptomatic infections — Asymptomatic infections have also been described [35,51-53], but their frequency is unknown.
In a COVID-19 outbreak on a cruise ship where nearly all passengers and staff were screened for SARS-CoV-2, approximately 17 percent of the population on board tested positive as of February 20; about half of the 619 confirmed COVID-19 cases were asymptomatic at the time of diagnosis [54].
Even patients with asymptomatic infection may have objective clinical abnormalities [22,55]. As an example, in a study of 24 patients with asymptomatic infection who all underwent chest computed tomography (CT), 50 percent had typical ground-glass opacities or patchy shadowing, and another 20 percent had atypical imaging abnormalities [22]. Five patients developed low-grade fever, with or without other typical symptoms, a few days after diagnosis.
Clinical manifestations
Initial presentation — Pneumonia appears to be the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging [34,38-40]. There are no specific clinical features that can yet reliably distinguish COVID-19 from other viral respiratory infections.
In a study describing 138 patients with COVID-19 pneumonia in Wuhan, the most common clinical features at the onset of illness were [40]:
●Fever in 99 percent
●Fatigue in 70 percent
●Dry cough in 59 percent
●Anorexia in 40 percent
●Myalgias in 35 percent
●Dyspnea in 31 percent
●Sputum production in 27 percent
Other cohort studies of patients from Wuhan with confirmed COVID-19 have reported a similar range of clinical findings [38,40,56,57]. However, fever might not be a universal finding. In one study, fever was reported in almost all patients, but approximately 20 percent had a very low grade fever <100.4°F/38°C [38]. In another study of 1099 patients from Wuhan and other areas in China, fever (defined as an axillary temperature over 99.5°F/37.5°C) was present in only 44 percent on admission but was ultimately noted in 89 percent during the hospitalization [34].
Other, less common symptoms have included headache, sore throat, and rhinorrhea. In addition to respiratory symptoms, gastrointestinal symptoms (eg, nausea and diarrhea) have also been reported in some patients, but these are relatively uncommon [38,40].
Reports of cohorts in locations outside of Wuhan have described similar clinical findings, although some have suggested that milder illness may be more common [58-60]. As an example, in a study of 62 patients with COVID-19 in the Zhejiang province of China, all but one had pneumonia, but only two developed dyspnea, and only one warranted mechanical ventilation [59].
Course and complications — As above, symptomatic infection can range from mild to critical. (See 'Spectrum of illness severity' above.)
Some patients with initially mild symptoms may progress over the course of a week. In one study of 138 patients hospitalized in Wuhan for pneumonia due to SARS-CoV-2, dyspnea developed after a median of five days since the onset of symptoms, and hospital admission occurred after a median of seven days of symptoms [40]. In another study, the median time to dyspnea was eight days [38].
Acute respiratory distress syndrome (ARDS) is a major complication in patients with severe disease. In the study of 138 patients described above, ARDS developed in 20 percent after a median of eight days, and mechanical ventilation was implemented in 12.3 percent [40]. In another study of 201 hospitalized patients with COVID-19 in Wuhan, 41 percent developed ARDS; age greater than 65 years, diabetes mellitus, and hypertension were each associated with ARDS [61].
Other complications have included arrhythmias, acute cardiac injury, and shock. In one study, these were reported in 17, 7, and 9 percent, respectively [40].
According to the WHO, recovery time appears to be around two weeks for mild infections and three to six weeks for severe disease [4].
Laboratory findings — In patients with COVID-19, the white blood cell count can vary. Leukopenia, leukocytosis, and lymphopenia have been reported, although lymphopenia appears most common [24,38-40]. Elevated lactate dehydrogenase and ferritin levels are common, and elevated aminotransferase levels have also been described. On admission, many patients with pneumonia have normal serum procalcitonin levels; however, in those requiring ICU care, they are more likely to be elevated [38-40].
High D-dimer levels and more severe lymphopenia have been associated with mortality [39].
Imaging findings — Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with or without consolidative abnormalities, consistent with viral pneumonia [57,62]. Case series have suggested that chest CT abnormalities are more likely to be bilateral, have a peripheral distribution, and involve the lower lobes. Less common findings include pleural thickening, pleural effusion, and lymphadenopathy.
Chest CT may be helpful in making the diagnosis, but no finding can completely rule in or rule out the possibility of COVID-19. In a study of 1014 patients in Wuhan who underwent both reverse-transcription polymerase chain reaction (RT-PCR) testing and chest CT for evaluation of COVID-19, a "positive" chest CT for COVID-19 (as determined by a consensus of two radiologists) had a sensitivity of 97 percent, using the PCR tests as a reference; however, specificity was only 25 percent [63]. The low specificity may be related to other etiologies causing similar CT findings. In another study comparing chest CTs from 219 patients with COVID-19 in China and 205 patients with other causes of viral pneumonia in the United States, COVID-19 cases were more likely to have a peripheral distribution (80 versus 57 percent), ground-glass opacities (91 versus 68 percent), fine reticular opacities (56 versus 22 percent), vascular thickening (59 versus 22 percent), and reverse halo sign (11 versus 1 percent), but less likely to have a central and peripheral distribution (14 versus 35 percent), air bronchogram (14 versus 23 percent), pleural thickening (15 versus 33 percent), pleural effusion (4 versus 39 percent), and lymphadenopathy (2.7 versus 10 percent) [64]. A group of radiologists in that study was able to distinguish COVID-19 with high specificity but moderate sensitivity.
In one report of 21 patients with laboratory-confirmed COVID-19 who did not develop severe respiratory distress, lung abnormalities on chest imaging were most severe approximately 10 days after symptom onset [56]. However, chest CT abnormalities have also been identified in patients prior to the development of symptoms and even prior to the detection of viral RNA from upper respiratory specimens [57,65].
EVALUATION AND DIAGNOSIS
Clinical suspicion and criteria for testing — The approach to initial management should focus on early recognition of suspect cases, immediate isolation, and institution of infection control measures. At present, the possibility of COVID-19 should be considered primarily in patients with fever and/or respiratory tract symptoms (eg, cough, dyspnea) who have had any of the following in the prior 14 days:
●Close contact with a confirmed or suspected case of COVID-19, including through work in health care settings. Close contact includes being within approximately six feet (about two meters) of a patient for a prolonged period of time while not wearing personal protective equipment or having direct contact with infectious secretions while not wearing personal protective equipment.
●Residence in or travel to areas where widespread community transmission has been reported (eg, China, South Korea, most of Europe [including Italy], Iran, Japan). (See 'Geographic distribution' above.)
●Potential exposure through attendance at events or spending time in specific settings where COVID-19 cases have been reported.
The possibility of COVID-19 should also be considered in patients with severe lower respiratory tract illness when an alternative etiology cannot be identified, even if there has been no clear exposure.
When COVID-19 is suspected, infection control measures should be implemented and public health officials notified. Patients who do not need emergent care should be encouraged to call prior to presenting to a health care facility for evaluation. Many patients can be evaluated regarding the need for testing over the phone. Infection control precautions are discussed elsewhere. (See 'Infection control for suspected or confirmed cases' below.)
The specific case definitions and clinical criteria for pursuing diagnostic evaluation differ slightly between expert groups.
●The United States Centers for Disease Control and Prevention (CDC) notes that the decision to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be based on clinical judgment and reminds clinicians that most patients with confirmed COVID-19 have fever (subjective or confirmed) and/or symptoms of acute respiratory illness (eg cough, dyspnea). This guidance expands its previous criteria to potentially include a wider group of symptomatic patients. In areas where testing capacity is limited, public health officials can guide prioritization of testing. The CDC suggests prioritizing hospitalized patients to inform infection control decisions, symptomatic individuals who have a higher risk of poor outcomes (eg, age ≥65 years, chronic medical condition, immunocompromising conditions), and those with high exposure risk (eg, recent travel to specific locations, contact with patients with COVID-19, or being a health care worker) [66]. Details can be found on the CDC website. An approach to suspected cases when testing is not available is discussed elsewhere. (See 'COVID-19 testing not readily available' below.)
●Case definitions from the World Health Organization are found in its technical guidance online.
●Case definitions from the European Centre for Disease Prevention and Control are found on its website.
Laboratory testing — Patients who meet the criteria for suspect cases, as discussed above, should undergo testing for SARS-CoV-2 (the virus that causes COVID-19), in addition to testing for other respiratory pathogens (eg, influenza, respiratory syncytial virus). (See "Diagnostic approach to community-acquired pneumonia in adults", section on 'Diagnostic testing for microbial etiology'.)
In the United States, the CDC recommends collection of a nasopharyngeal swab specimen to test for SARS-CoV-2 [67]. An oropharyngeal swab can be collected but is not essential; if collected, it should be placed in the same container as the nasopharyngeal specimen. Sputum should only be collected from patients with productive cough; induction of sputum is not indicated.
SARS-CoV-2 RNA is detected by reverse-transcription polymerase chain reaction (RT-PCR); in the United States, testing is performed by the CDC or a CDC-qualified lab [68]. A positive test for SARS-CoV-2 confirms the diagnosis of COVID-19. If initial testing is negative but the suspicion for COVID-19 remains, the WHO recommends resampling and testing from multiple respiratory tract sites [69]. The accuracy and predictive values of SARS-CoV-2 testing have not been systematically evaluated. Negative RT-PCR tests on oropharyngeal swabs despite CT findings suggestive of viral pneumonia have been reported in some patients who ultimately tested positive for SARS-CoV-2 [65].
For safety reasons, specimens from a patient with suspected or documented COVID-19 should not be submitted for viral culture.
The importance of testing for other pathogens was highlighted in a report of 210 symptomatic patients with suspected COVID-19; 30 tested positive for another respiratory viral pathogen, and 11 tested positive for SARS-CoV-2 [37].
MANAGEMENT
Site of care
Home care — Home management is appropriate for patients with mild infection who can be adequately isolated in the outpatient setting [24,70,71]. Management of such patients should focus on prevention of transmission to others and monitoring for clinical deterioration, which should prompt hospitalization.
Outpatients with COVID-19 should stay at home and try to separate themselves from other people and animals in the household. They should wear a facemask when in the same room (or vehicle) as other people and when presenting to health care settings. Disinfection of frequently touched surfaces is also important, as discussed elsewhere. (See 'Environmental disinfection' below.)
The United States Centers for Disease Control and Prevention (CDC) has issued recommendations on discontinuation of home isolation, which include both test-based and non-test-based strategies [72,73]. The choice of strategy depends upon the patient population (eg, immunocompromised versus nonimmunocompromised), the availability of testing supplies, and access to testing.
●When a test-based strategy is used, patients may discontinue home isolation when there is:
•Resolution of fever without the use of fever-reducing medications AND
•Improvement in respiratory symptoms (eg, cough, shortness of breath) AND
•Negative results of a US Food and Drug Administration (FDA) Emergency Use Authorized molecular assay for COVID-19 from at least two consecutive nasopharyngeal swab specimens collected ≥24 hours apart (total of two negative specimens)
●When a non-test-based strategy is used, patients may discontinue home isolation when the following criteria are met:
•At least seven days have passed since symptoms first appeared AND
•At least three days (72 hours) have passed since recovery of symptoms (defined as resolution of fever without the use of fever-reducing medications and improvement in respiratory symptoms [eg, cough, shortness of breath])
In some cases, patients may have had laboratory-confirmed COVID-19, but they did not have any symptoms when they were tested. In such patients, home isolation may be discontinued when at least seven days have passed since the date of their first positive COVID-19 test so long as there was no evidence of subsequent illness.
The use of non-test-based strategies that use time since illness onset and time since recovery as the criteria for discontinuing precautions is based upon findings that transmission is most likely to occur in the early stage of infection. However, data are limited, particularly in immunocompromised patients, and this strategy may not prevent all instances of secondary spread [72,73]. (See 'Transmission' above.)
More detailed interim recommendations on home management of patients with COVID-19 can be found on the World Health Organization (WHO) and CDC websites [71,74,75].
Hospital care — Some patients with suspected or documented COVID-19 have severe disease that warrants hospital care. Management of such patients consists of ensuring appropriate infection control, as below (see 'Infection control for suspected or confirmed cases' below), and supportive care. Clinical guidance can be found on the WHO and CDC websites [24,70].
Patients with severe disease often need oxygenation support. High-flow oxygen and noninvasive positive pressure ventilation have been used, but the safety of these measures is uncertain, and they should be considered aerosol-generating procedures that warrant specific isolation precautions. (See 'Infection control for suspected or confirmed cases' below.)
Some patients may develop acute respiratory distress syndrome and warrant intubation with mechanical ventilation; extracorporeal membrane oxygenation may be indicated in patients with refractory hypoxia. Management of acute respiratory distress syndrome is discussed in detail elsewhere. (See "Acute respiratory distress syndrome: Supportive care and oxygenation in adults" and "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults" and "Ventilator management strategies for adults with acute respiratory distress syndrome" and "Prone ventilation for adult patients with acute respiratory distress syndrome" and "Extracorporeal membrane oxygenation (ECMO) in adults".)
Limited role of glucocorticoids — The WHO and CDC recommend glucocorticoids not be used in patients with COVID-19 pneumonia unless there are other indications (eg, exacerbation of chronic obstructive pulmonary disease) [24,70]. Glucocorticoids have been associated with an increased risk for mortality in patients with influenza and delayed viral clearance in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Although they were widely used in management of severe acute respiratory syndrome (SARS), there was no good evidence for benefit, and there was persuasive evidence of adverse short- and long-term harm [76]. (See "Treatment of seasonal influenza in adults", section on 'Adjunctive therapies' and "Middle East respiratory syndrome coronavirus: Treatment and prevention", section on 'Treatment'.)
Use of NSAIDs — Some clinicians have suggested the use of non-steroidal anti-inflammatory drugs (NSAIDs) early in the course of disease may have a negative impact on disease outcome [77,78]. These concerns are based on anecdotal reports of a few young patients who received NSAIDs early in the course of infection and experienced severe disease, as well as the theoretic concern that the anti-inflammatory properties associated with NSAIDs could have a negative impact on the patient's immune response. In light of these concerns, some providers are using acetaminophen in place of NSAIDs for reduction of fever; however, the European Medicines Agency (EMA) and the WHO do not recommend that NSAIDs be avoided when clinically indicated [79,80].
Investigational agents — A number of investigational agents are being explored for antiviral treatment of COVID-19, and enrollment in clinical trials should be discussed with patients or their proxies. A registry of international clinical trials can be found on the WHO website and at clinicaltrials.gov.
Certain investigational agents have been described in observational series or are being used anecdotally based on in vitro or extrapolated evidence. It is important to acknowledge that there are no controlled data supporting the use of any of these agents, and their efficacy for COVID-19 is unknown.
●Remdesivir – Several randomized trials are underway to evaluate the efficacy of remdesivir for moderate or severe COVID-19 [81]. Remdesivir is a novel nucleotide analogue that has activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and related coronaviruses (including SARS and MERS-CoV) both in vitro and in animal studies [82,83]. The compassionate use of remdesivir through an investigational new drug application was described in a case report of one of the first patients with COVID-19 in the United States [84]. Any clinical impact of remdesivir on COVID-19 remains unknown.
●Chloroquine/hydroxychloroquine – Both chloroquine and hydroxychloroquine inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more potent antiviral activity [85]. A number of clinical trials are underway in China to evaluate the use of chloroquine or hydroxychloroquine for COVID-19 [86].
●Lopinavir-ritonavir – This combined protease inhibitor, which has primarily been used for HIV infection, has in vitro activity against the SARS-CoV [87] and appears to have some activity against MERS-CoV in animal studies [88]. Although the use of this agent for treatment of COVID-19 has been described in case reports [89-91], there was no difference in time to clinical improvement or mortality at 28 days in a randomized trial of 199 patients with severe COVID-19 given lopinavir-ritonavir (400/100 mg) twice daily for 14 days in addition to standard care versus those who received standard of care alone [92].
●Tocilizumab – Treatment guidelines from China's National Health Commission include the IL-6 inhibitor tocilizumab for patients with severe COVID-19 and elevated IL-6 levels; the agent is being evaluated in a clinical trial [93].
Other interventions of interest but with limited or no clinical data include interferon beta and convalescent serum.
PREVENTION
In the health care setting
Screening and precautions for fever or respiratory symptoms — Screening patients for clinical manifestations consistent with COVID-19 (eg, fever, cough, dyspnea) prior to entry into a health care facility can help identify those who may warrant additional infection control precautions. This can be done over the phone before the patient actually presents to a facility. Any individual with these manifestations should be advised to wear a facemask. Separate waiting areas for patients with respiratory symptoms should be designated, if possible, at least six feet away from the regular waiting areas.
Symptomatic patients should also be asked about recent travel or potential COVID-19 exposure in the prior 14 days to determine the need for evaluation for COVID-19. (See 'Clinical suspicion and criteria for testing' above.)
In some settings, such as long-term care facilities, the United States Centers for Disease Control and Prevention (CDC) recommends that standard, contact, and droplet precautions in addition to eye protection be used for any patient with an undiagnosed respiratory infection who is not under consideration for COVID-19 [94]. This may help reduce the risk of spread from unsuspected COVID-19 cases. Infection control precautions for suspect COVID-19 cases are discussed below.
In locations where community transmission is ongoing, postponing elective procedures or non-urgent visits and using virtual (eg, through video communication) visits may be useful strategies to reduce the risk of exposure [95].
Infection control for suspected or confirmed cases — Infection control to limit transmission is an essential component of care in patients with suspected or documented COVID-19. In one report of 138 patients with COVID-19 in China, it was estimated that 43 percent acquired infection in the hospital setting [40].
Individuals with suspected infection in the community should be advised to wear a medical mask to contain their respiratory secretions prior to seeking medical attention. (See 'Evaluation and diagnosis' above.)
In the health care setting, the World Health Organization (WHO) and CDC recommendations for infection control for suspected or confirmed infections differ slightly:
●The WHO recommends standard, contact, and droplet precautions (ie, gown, gloves, and mask), with eye or face protection [96]. The addition of airborne precautions (ie, respirator) is warranted during aerosol-generating procedures (as detailed below).
The CDC recommends that patients with suspected or confirmed COVID-19 be placed in a single-occupancy room with a closed door and dedicated bathroom [95]. The patient should wear a facemask if being transported out of the room (eg, for studies that cannot be performed in the room). An airborne infection isolation room (ie, a single-patient negative pressure room) should be reserved for patients undergoing aerosol-generating procedures (as detailed below).
Any personnel entering the room of a patient with suspected or confirmed COVID-19 should wear the appropriate personal protection equipment: gown, gloves, eye protection, and a respirator (eg, an N95 respirator). If supply of respirators is limited, the CDC acknowledges that facemasks are an acceptable alternative (in addition to contact precautions and eye protection), but respirators should be worn during aerosol-generating procedures [95].
Aerosol-generating procedures include tracheal intubation, noninvasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual ventilation before intubation, upper endoscopy, and bronchoscopy. Nasopharyngeal or oropharyngeal specimen collection is not considered an aerosol-generating procedure.
For health care workers who have had a potential exposure to COVID-19, the CDC has provided guidelines for work restriction and monitoring. The approach depends upon the duration of exposure, the patient's symptoms, whether the patient was wearing a facemask, the type of personal protective equipment used by the provider, and whether an aerosol-generating procedure was performed.
Links to additional infection control guidelines are found below. (See 'Society guideline links' below.)
Discontinuation of precautions — The decision to discontinue infection control precautions for patients with COVID-19 should be made on a case-by-case basis in consultation with experts in infection prevention and control and public health officials. Factors to inform this decision include resolution of clinical signs and symptoms and negative results of reverse-transcription polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on two sequential paired nasopharyngeal and throat specimens (ie, four specimens total, each handled separately), with each pair collected ≥24 hours apart [97].
Positive RT-PCR tests for SARS-CoV-2 were reported in four laboratory-confirmed COVID-19 patients after they had clinically improved and tested negative on two consecutive tests [98]. The clinical significance of this finding is uncertain; it is unknown whether these individuals continued to shed infectious virus.
Environmental disinfection — To help reduce the spread of COVID-19 virus, environmental infection control procedures should also be implemented [71,75,95,96,99]. In United States health care settings, the CDC states routine cleaning and disinfection procedures are appropriate for COVID-19 virus [95].
Products approved by the Environmental Protection Agency (EPA) for emerging viral pathogens should be used; a list of EPA-registered products can be found here. Specific guidance on environmental measures, including those used in the home setting, is available on the CDC and WHO websites. Additional information is also found in a separate topic review. (See "Coronaviruses", section on 'Treatment and prevention'.)
The importance of environmental disinfection was illustrated in a study from Singapore, in which viral RNA was detected on nearly all surfaces tested (handles, light switches, bed and handrails, interior doors and windows, toilet bowl, sink basin) in the airborne infection isolation room of a patient with symptomatic mild COVID-19 prior to routine cleaning [100]. Viral RNA was not detected on similar surfaces in the rooms of two other symptomatic patients following routine cleaning (with sodium dichloroisocyanurate). Of note, viral RNA detection does not necessarily indicate the presence of infectious virus.
It is unknown how long SARS-CoV-2 can persist on surfaces [14,99,101]; other coronaviruses have been tested and may survive on inanimate surfaces for up to six to nine days without disinfection. In a study evaluating the survival of viruses dried on a plastic surface at room temperature, a specimen containing SARS-CoV (a virus closely related to SARS-CoV-2) had detectable infectivity at six but not nine days [101]. However, in a systematic review of similar studies, various disinfectants (including ethanol at concentrations between 62 and 71 percent) inactivated a number of coronaviruses related to SARS-CoV-2 within one minute [99].
Preventing exposure in the community — The following general measures are recommended to reduce transmission of infection:
●Diligent hand washing, particularly after touching surfaces in public. Use of hand sanitizer that contains at least 60 percent alcohol is a reasonable alternative if the hands are not visibly dirty.
●Respiratory hygiene (eg, covering the cough or sneeze).
●Avoiding touching the face (in particular eyes, nose, and mouth).
●Avoiding crowds (particularly in poorly ventilated spaces) if possible and avoiding close contact with ill individuals.
●Cleaning and disinfecting objects and surfaces that are frequently touched. The CDC has issued guidance on disinfection in the home setting; a list of EPA-registered products can be found here.
In particular, older adults and individuals with chronic medical conditions should be encouraged to follow these measures.
If SARS-CoV-2 is prevalent in the community, residents should be encouraged to practice social distancing by staying home as much as possible. In the United States, the CDC has provided guidance for cancelling and postponing gatherings [102].
For people without respiratory symptoms, wearing a medical mask in the community is not recommended, even if COVID-19 is prevalent in the area [2]; wearing a mask does not decrease the importance of other general measures to prevent infection, and it may result in unnecessary cost and supply problems [103].
Individuals who are caring for patients with suspected or documented COVID-19 at home, however, should wear a tightly fitting medical mask when in the same room as that patient.
Individuals who develop an acute respiratory illness (eg, with fever and/or respiratory symptoms) should be encouraged to stay home from school or work for the duration of the illness. Some may warrant evaluation for COVID-19. (See 'Clinical suspicion and criteria for testing' above.)
The CDC has included recommended measures to prevent spread in the community on its website.
Managing asymptomatic individuals with potential exposure — Individuals who have had travel to high-risk areas or are contacts of patients with suspected or confirmed COVID-19 should be monitored for development of consistent symptoms and signs (fever, cough, or dyspnea). Such clinical manifestations should prompt at least self-isolation with social distancing and clinician assessment for the need for medical evaluation. (See 'Clinical suspicion and criteria for testing' above.)
In the United States, the level of risk (based on the travel location or the type of contact) informs whether monitoring and isolation are done by the individual or with the involvement of public health personnel. Categories of risk and the suggested monitoring and isolation strategies can be found on the CDC website.
Global public health measures — On January 30, 2020, the WHO declared the COVID-19 outbreak a public health emergency of international concern and, in March 2020, began to characterize it as a pandemic in order to emphasize the gravity of the situation and urge all countries to take action in detecting infection and preventing spread. The WHO has indicated three priorities for countries: protecting health workers, engaging communities to protect those at highest risk of severe disease (eg, older adults and those with medical comorbidities), and supporting vulnerable countries in containing infection [4].
The WHO does not recommend international travel restrictions but does acknowledge that movement restriction may be temporarily useful in some settings. The WHO advises exit screening for international travelers from areas with ongoing transmission of COVID-19 virus to identify individuals with fever, cough, or potential high-risk exposure [104,105]. Many countries also perform entry screening (eg, temperature, assessment for signs and symptoms). More detailed travel information is available on the WHO website.
In the United States, the CDC currently recommends that individuals avoid all nonessential travel to mainland China, Iran, most European countries (including Italy), and South Korea [106]. Because risk of travel changes rapidly, those coming from other countries should check United States government web sites for possible restrictions on arrival. The CDC has released travel advisories regarding other locations where community transmission has been reported [106]. The CDC website provides updated guidance on travel restrictions as well as risk assessment and management of persons with a suspected exposure to COVID-19.
Although many cases of COVID-19 can be detected through entry screening, some may be missed. As an example, in Germany, 114 travellers returning from Wuhan were considered to be asymptomatic during entry screening but, when tested for COVID-19 virus by RT-PCR, two tested positive [107]. However, the role of asymptomatic patients in transmitting infection to others, and thus the value of PCR testing of asymptomatic individuals on entry, remains unclear. (See 'Transmission' above.)
SPECIAL SITUATIONS
Pregnant and breastfeeding women — Minimal information is available regarding COVID-19 during pregnancy. Intrauterine or perinatal transmission has not been identified [108-111]. In two reports including a total of 18 pregnant women with suspected or confirmed COVID-19 pneumonia, there was no laboratory evidence of transmission of the virus to the neonate [108,109]. However, neonatal cases of infection have been documented [112,113]. In one case, the diagnosis was made at day 17 of life after close contact with the infant's mother and a maternity matron who were both infected with the virus. The other case was diagnosed 36 hours after birth; the source and time of transmission in that case were unclear.
The approach to prevention, evaluation, diagnosis, and treatment of pregnant women with suspected COVID-19 should be similar to that in nonpregnant individuals (as described above), with consideration that pregnant women with other potentially severe respiratory infections, such as influenza, severe acute respiratory syndrome (SARS)-CoV, or Middle East respiratory syndrome (MERS)-CoV, appear to be more vulnerable to developing severe disease.
Cesarean delivery is performed for standard obstetric indications. In symptomatic women with suspected or confirmed COVID-19, one expert group suggested leaving the vernix caseosa in place for 24 hours after birth, since it contains antimicrobial peptides [114]. Additionally, the American College of Obstetricians and Gynecologists (ACOG) specifies that infants born to mothers with confirmed COVID-19 should be considered a patient under investigation and appropriately isolated and evaluated [115]. (See 'Evaluation and diagnosis' above.)
It is unknown whether the virus can be transmitted through breast milk. The only report of testing found no virus in the maternal milk of six patients [108]. However, droplet transmission could occur through close contact during breastfeeding. Thus, mothers with confirmed COVID-19 or symptomatic mothers with suspected COVID-19 should take precautions to prevent transmission to the infant during breastfeeding (including assiduous hand hygiene and use of a facemask) [71,115]. Alternatively, to minimize direct contact, the infant can be fed expressed breastmilk by another caregiver until the mother has recovered, provided that the other caregiver is healthy and follows hygiene precautions.
Women who choose not to breastfeed must take similar precautions to prevent transmission through close contact when formula is used.
COVID-19 testing not readily available — In some cases, testing for COVID-19 may not be accessible, particularly for individuals who have a compatible but mild illness that does not warrant hospitalization and do not have a known COVID-19 exposure or high-risk travel history.
In the United States, there is limited official guidance for this situation, and the approach may depend on the prevalence of COVID-19 in the area. If the clinician has sufficient concern for possible COVID-19 (eg, there is community transmission), it is reasonable to advise the patient to self-isolate at home (if hospitalization is not warranted) and alert the clinician about worsening symptoms. The optimal duration of home isolation in such cases is uncertain. A discussion of when home isolation can be discontinued in patients with confirmed COVID-19 can be found above. (See 'Home care' above.)
Managing chronic medications
Patients receiving ACE inhibitors/ARBs — Patients receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) should continue treatment with these agents. This approach is supported by multiple guideline panels [116-120].
There has been speculation that patients with COVID-19 who are receiving these agents may be at increased risk for adverse outcomes [121,122]. Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 [123], and renin-angiotensin-aldosterone system inhibitors can increase ACE2 levels. Although patients with cardiovascular disease, hypertension, and diabetes may have a more severe clinical course in the setting of infection with SARS-CoV-2, there is no evidence to support an association with these agents. In addition, stopping these agents in some patients may exacerbate comorbid cardiovascular or kidney disease and lead to increased mortality [124].
Patients receiving immunomodulatory agents — Immunocompromised patients with COVID-19 are at increased risk for severe disease, and the decision to discontinue prednisone, biologics, or other immunosuppressive drugs in the setting of infection must be determined on a case-by-case basis. (See 'Management' above.)
For individuals with underlying conditions who require treatment with these agents and are without evidence of COVID-19, there is no evidence that routinely discontinuing treatment is of any benefit. In addition, discontinuing these medications may result in loss of response when the agent is reintroduced. This approach is supported by statements from American and other dermatology, rheumatology, and gastroenterology societies [125-128].
SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Coronavirus disease 2019 (COVID-19)".)
INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Coronavirus disease 2019 (COVID-19) (The Basics)")
SUMMARY AND RECOMMENDATIONS
●In late 2019, a novel coronavirus, now designated SARS-CoV-2, was identified as the cause of an outbreak of acute respiratory illness in Wuhan, a city in China. In February 2020, the World Health Organization (WHO) designated the disease COVID-19, which stands for coronavirus disease 2019. (See 'Introduction' above.)
●Since the first reports of COVID-19, infection has spread to include more than 80,000 cases in China and increasing cases worldwide, prompting the WHO to declare a public health emergency in late January 2020 and characterize it as a pandemic in March 2020. The rate of new infections outside of China has surpassed that within China as epidemics have grown in other countries. (See 'Epidemiology' above.)
●The possibility of COVID-19 should be considered primarily in patients with fever and/or respiratory tract symptoms who have had recent close contact with a confirmed or suspected case of COVID-19, who reside in or have recently (within the prior 14 days) traveled to areas where community transmission has been reported (eg, China, South Korea, most of Europe [including Italy], Iran, Japan) or who have had potential exposure from specific settings where COVID-19 cases have been reported. Clinicians should also be aware of the possibility of COVID-19 in patients with severe respiratory illness when no other etiology can be identified. (See 'Clinical features' above and 'Evaluation and diagnosis' above.)
●Upon suspicion of COVID-19, infection control measures should be implemented and public health officials notified. In health care settings in the United States, the Centers for Disease Control and Prevention (CDC) recommends a single-occupancy room for patients and gown, gloves, eye protection, and a respirator (or facemask as an alternative) for health care personnel. (See 'Infection control for suspected or confirmed cases' above.)
●In addition to testing for other respiratory pathogens, a nasopharyngeal swab specimen should be collected for reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. (See 'Evaluation and diagnosis' above.)
●Management consists of supportive care. Home management may be possible for patients with mild illness who can be adequately isolated in the outpatient setting. (See 'Management' above.)
●To reduce the risk of transmission in the community, individuals should be advised to wash hands diligently, practice respiratory hygiene (eg, cover their cough), and avoid crowds and close contact with ill individuals, if possible. Facemasks are not routinely recommended for asymptomatic individuals to prevent exposure in the community. Social distancing is advised, particularly in locations that have community transmission. (See 'Preventing exposure in the community' above.)
●Interim guidance has been issued by the WHO and by the CDC. These are updated on an ongoing basis. (See 'Society guideline links' above.)
Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

  1. World Health Organization. Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020 (Accessed on February 12, 2020).
  2. Centers for Disease Control and Prevention. 2019 Novel coronavirus, Wuhan, China. Information for Healthcare Professionals. https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html (Accessed on February 14, 2020).
  3. World Health Organization. Novel Coronavirus (2019-nCoV) technical guidance. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance (Accessed on February 14, 2020).
  4. WHO Director-General's opening remarks at the media briefing on COVID-19 - 24 February 2020 https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---24-february-2020 (Accessed on February 26, 2020).
  5. National Health Commission of the People's Republic of China. New coronavirus cases rise to 571 in Chinese mainland. January 23, 2020. http://en.nhc.gov.cn/2020-01/23/c_76004.htm (Accessed on January 23, 2020).
  6. European Centre for Disease Prevention and Control. Novel coronavirus in China. https://www.ecdc.europa.eu/en/novel-coronavirus-china (Accessed on January 23, 2020).
  7. World Health Organization. WHO Disease outbreak news: Novel Coronavirus – Republic of Korea (ex-China). January 21, 2020. https://www.who.int/csr/don/21-january-2020-novel-coronavirus-republic-of-korea-ex-china/en/ (Accessed on January 21, 2020).
  8. Centers for Disease Control and Prevention. First travel-related case of 2019 novel coronavirus detected in United States, January 21, 2020. https://www.cdc.gov/media/releases/2020/p0121-novel-coronavirus-travel-case.html (Accessed on January 21, 2020).
  9. Centers for Disease Control and Prevention. Second travel-related case of 2019 novel coronavirus detected in United States, January 24, 2020. https://www.cdc.gov/media/releases/2020/p0124-second-travel-coronavirus.html (Accessed on January 24, 2020).
  10. European Centre for Disease Prevention and Control. Geographical distribution of 2019-nCov cases. https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases (Accessed on January 26, 2020).
  11. Centers for Disease Control and Prevention. 2019 Novel Coronavirus (2019-nCoV) in the US. https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html (Accessed on February 10, 2020).
  12. WHO. Coronavirus disease 2019 (COVID-19) Situation Report - 36. February 25, 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200225-sitrep-36-covid-19.pdf?sfvrsn=2791b4e0_2 (Accessed on February 26, 2020).
  13. World Health Organization. Novel coronavirus situation report -2. January 22, 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200122-sitrep-2-2019-ncov.pdf (Accessed on January 23, 2020).
  14. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med 2020.
  15. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020.
  16. Report of the WHO-China Joint Mission on Coronavirus DIsease 2019 (COVID-2019). February 16-24, 2020. http://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf (Accessed on March 04, 2020).
  17. Burke RM, Midgley CM, Dratch A, et al. Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 — United States, January–February 2020. MMWR Morb Mortal Wkly Rep 2020; 69.
  18. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med 2020; 382:970.
  19. Kupferschmidt K. Study claiming new coronavirus can be transmitted by people without symptoms was flawed. Science. February 3, 2020. https://www.sciencemag.org/news/2020/02/paper-non-symptomatic-patient-transmitting-coronavirus-wrong (Accessed on February 04, 2020).
  20. Yu P, Zhu J, Zhang Z, et al. A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period. J Infect Dis 2020.
  21. Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA 2020.
  22. Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci 2020.
  23. Li Z, Yi Y, Luo X, et al. Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis. J Med Virol 2020.
  24. Centers for Disease Control and Prevention. Interim Clinical Guidance for Management of Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) Infection, Updated February 12, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html (Accessed on February 14, 2020).
  25. Tang A, Tong ZD, Wang HL, et al. Detection of Novel Coronavirus by RT-PCR in Stool Specimen from Asymptomatic Child, China. Emerg Infect Dis 2020; 26.
  26. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020.
  27. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579:270.
  28. https://www.biorxiv.org/content/10.1101/2020.02.07.937862v1, (Accessed on February 12, 2020).
  29. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020; 382:727.
  30. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395:565.
  31. Perlman S. Another Decade, Another Coronavirus. N Engl J Med 2020; 382:760.
  32. Tang X, Wu C, Li X, et al. On the origin and continuing evolution of SARS-CoV-2. National Science Review 2020.
  33. Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 2020.
  34. Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020.
  35. Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395:514.
  36. Lauer S, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med 2020.
  37. Bajema KL, Oster AM, McGovern OL, et al. Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020. MMWR Morb Mortal Wkly Rep 2020; 69:166.
  38. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:497.
  39. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395:507.
  40. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020.
  41. Liu K, Fang YY, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl) 2020.
  42. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020.
  43. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA 2020.
  44. Zu F, Yu T, Du R, at al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020.
  45. Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA 2020.
  46. KCDC. Updates on COVID-19 in Korea. March 14, 2020. https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030 (Accessed on March 14, 2020).
  47. Severe outcomes among patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020 https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2. (Accessed on March 19, 2020).
  48. Cui Y, Tian M, Huang D, et al. A 55-Day-Old Female Infant infected with COVID 19: presenting with pneumonia, liver injury, and heart damage. J Infect Dis 2020.
  49. Cai J, Xu J, Lin D, et al. A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis 2020.
  50. Liu W, Zhang Q, Chen J, et al. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. N Engl J Med 2020.
  51. Liu YC, Liao CH, Chang CF, et al. A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan. N Engl J Med 2020; 382:1070.
  52. Wei M, Yuan J, Liu Y, et al. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. JAMA 2020.
  53. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report – 28. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200217-sitrep-28-covid-19.pdf?sfvrsn=a19cf2ad_2 (Accessed on February 18, 2020).
  54. Japanese National Institute of Infectious Diseases. Field Briefing: Diamond Princess COVID-19 Cases, 20 Feb Update. https://www.niid.go.jp/niid/en/2019-ncov-e/9417-covid-dp-fe-02.html (Accessed on March 01, 2020).
  55. Wang Y, Liu Y, Liu L, et al. Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen, China. J Infect Dis 2020.
  56. Pan F, Ye T, Sun P, et al. Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia. Radiology 2020; :200370.
  57. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020.
  58. Chang, Lin M, Wei L, et al. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA 2020.
  59. Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 2020; 368:m606.
  60. Wu J, Liu J, Zhao X, et al. Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study. Clin Infect Dis 2020.
  61. Wu C, Chen X, Cai Y et. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 2020.
  62. Zhao W, Zhong Z, Xie X, et al. Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study. AJR Am J Roentgenol 2020; :1.
  63. Ai T, Yang Z, Hou H, et al. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology 2020; :200642.
  64. Bai HX, Hsieh B, Xiong Z, et al. Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT. Radiology 2020; :200823.
  65. Xie X, Zhong Z, Zhao W, et al. Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology 2020; :200343.
  66. CDC, Updated Guidance on Evaluating and Testing Persons for COVID-19. HAN429. https://emergency.cdc.gov/han/2020/han00429.asp?deliveryName=USCDC_511-DM22015 (Accessed on March 09, 2020).
  67. Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under Investigation (PUIs) for Coronavirus Disease 2019 (COVID-19). February 14, 2020 https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html (Accessed on March 15, 2020).
  68. Patel A, Jernigan DB, 2019-nCoV CDC Response Team. Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak - United States, December 31, 2019-February 4, 2020. MMWR Morb Mortal Wkly Rep 2020; 69:140.
  69. WHO. Coronavirus disease (COVID-19) technical guidance: Surveillance and case definitions. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/surveillance-and-case-definitions (Accessed on February 28, 2020).
  70. World Health Organization. Novel Coronavirus (2019-nCoV) technical guidance: Patient management. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/patient-management (Accessed on February 02, 2020).
  71. World Health Organization. Home care for patients with suspected novel coronavirus (nCoV) infection presenting with mild symptoms and management of contacts. Updated February 4, 2020. https://www.who.int/publications-detail/home-care-for-patients-with-suspected-novel-coronavirus-(ncov)-infection-presenting-with-mild-symptoms-and-management-of-contacts (Accessed on February 14, 2020).
  72. United States Centers for Disease Control and Prevention. Discontinuation of home isolation for persons with COVID-19 (Interim Guidance). https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html (Accessed on March 17, 2020).
  73. United States Centers for Disease Control and Prevention. Discontinuation of In-Home isolation for immunocompromised persons with COVID-19 (Interim Guidance). https://www.cdc.gov/coronavirus/2019-ncov/hcp/ending-isolation.html (Accessed on March 18, 2020).
  74. Centers for Disease Control and Prevention. Interim Guidance for Implementing Home Care of People Not Requiring Hospitalization for 2019 Novel Coronavirus (2019-nCoV). Updated Janury 31, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-home-care.html (Accessed on February 04, 2020).
  75. Centers for Disease Control and Prevention. Interim guidance for persons who may have 2019 Novel Coronavirus (2019-nCoV) to prevent spread in homes and residential communities. https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-prevent-spread.html#First_heading (Accessed on February 06, 2020).
  76. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395:473.
  77. https://dgs-urgent.sante.gouv.fr/dgsurgent/inter/detailsMessageBuilder.do?id=30500&cmd=visualiserMessage (Accessed on March 19, 2020).
  78. Day M. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists. BMJ 2020; 368:m1086.
  79. Updated: WHO Now Doesn't Recommend Avoiding Ibuprofen For COVID-19 Symptoms https://www.sciencealert.com/who-recommends-to-avoid-taking-ibuprofen-for-covid-19-symptoms (Accessed on March 19, 2020).
  80. European Medicines Agency. EMA gives advice on the use of non-steroidal anti-inflammatories for COVID-19 https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19 (Accessed on March 19, 2020).
  81. Gilead. Gilead Sciences Statement on the Company’s Ongoing Response to the 2019 Novel Coronavirus (2019-nCoV). https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-the-company-ongoing-response-to-the-2019-new-coronavirus (Accessed on February 02, 2020).
  82. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017; 9.
  83. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30:269.
  84. Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med 2020; 382:929.
  85. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020.
  86. Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020.
  87. Groneberg DA, Poutanen SM, Low DE, et al. Treatment and vaccines for severe acute respiratory syndrome. Lancet Infect Dis 2005; 5:147.
  88. Chan JF, Yao Y, Yeung ML, et al. Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset. J Infect Dis 2015; 212:1904.
  89. Lim J, Jeon S, Shin HY, et al. Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR. J Korean Med Sci 2020; 35:e79.
  90. Wang Z, Chen X, Lu Y, et al. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends 2020; 14:64.
  91. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA 2020.
  92. Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 2020.
  93. Reuters. China approves use of Roche drug in battle against coronavirus complications. https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-of-roche-arthritis-drug-for-coronavirus-patients-idUSKBN20R0LF (Accessed on March 11, 2020).
  94. Centers for Disease Control and Prevention. Strategies to Prevent the Spread of COVID-19 in Long-Term Care Facilities (LTCF). https://www.cdc.gov/coronavirus/2019-ncov/healthcare-facilities/prevent-spread-in-long-term-care-facilities.html (Accessed on March 08, 2020).
  95. Centers for Disease Control and Prevention. Interim Infection Prevention and Control Recommendations for Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) or Patients Under Investigation for 2019-nCoV in Healthcare Settings. February 3, 2020. https://www.cdc.gov/coronavirus/2019-nCoV/hcp/infection-control.html (Accessed on March 11, 2020).
  96. World Health Organization. Infection prevention and control during health care when novel coronavirus (nCoV) infection is suspected. January 25, 2020. https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125 (Accessed on February 04, 2020).
  97. Centers for Disease Control and Prevention. Interim Considerations for Disposition of Hospitalized Patients with 2019-nCoV Infection. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html (Accessed on February 11, 2020).
  98. Lan L, Xu D, Ye G, et al. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA 2020.
  99. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect 2020; 104:246.
  100. Ong SWX, Tan YK, Chia PY, et al. Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient. JAMA 2020.
  101. Rabenau HF, Cinatl J, Morgenstern B, et al. Stability and inactivation of SARS coronavirus. Med Microbiol Immunol 2005; 194:1.
  102. United States Centers for Disease Control. Get your mass gatherings or large community events ready. https://www.cdc.gov/coronavirus/2019-ncov/community/large-events/mass-gatherings-ready-for-covid-19.html (Accessed on March 17, 2020).
  103. World Health Organization. Advice on the use of masks the community, during home care and in health care settings in the context of the novel coronavirus (2019-nCoV) outbreak. January 29, 2020. http://www.who.int/publications-detail/advice-on-the-use-of-masks-the-community-during-home-care-and-in-health-care-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak (Accessed on January 31, 2020).
  104. World Health Organization. Updated WHO advice for international traffic in relation to the outbreak of the novel coronavirus 2019-nCoV, 24 January 2020, https://www.who.int/ith/2020-24-01-outbreak-of-Pneumonia-caused-by-new-coronavirus/en/ (Accessed on January 26, 2020).
  105. World Health Organization. Key considerations for repatriation and quarantine of travellers in relation to the outbreak of novel coronavirus 2019-nCoV. February 11, 2020. https://www.who.int/ith/Repatriation_Quarantine_nCoV-key-considerations_HQ-final11Feb.pdf?ua=1 (Accessed on February 18, 2020).
  106. United States Centers for Disease Control and Prevention. Novel Coronavirus Information for Travel. https://www.cdc.gov/coronavirus/2019-ncov/travelers/index.html (Accessed on February 18, 2020).
  107. Hoehl S, Berger A, Kortenbusch M, et al. Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China. N Engl J Med 2020.
  108. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020; 395:809.
  109. Zhu H, Wang L, Fang C, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr 2020; 9:51.
  110. Wang X, Zhou Z, Zhang J, et al. A case of 2019 Novel Coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis 2020.
  111. Li Y, Zhao R, Zheng S, et al. Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China. Emerg Infect Dis 2020; 26.
  112. Qiao J. What are the risks of COVID-19 infection in pregnant women? Lancet 2020; 395:760.
  113. Wang S, Guo L, Chen L, et al. A case report of neonatal COVID-19 infection in China. Clin Infect Dis 2020.
  114. Baud D, Giannoni E, Pomar E, et al. COVID-19 in pregnant women. Lancet Infect Dis 2020.
  115. Practice Advisory: Novel Coronavirus 2019 (COVID-19) https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Novel-Coronavirus2019 (Accessed on March 17, 2020).
  116. Statement from the American Heart Association, the Heart Failure Society of America and the American College of Cardiology. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician. https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician (Accessed on March 18, 2020).
  117. European Societyof Hypertension. ESH Statement on COVID-19. https://www.eshonline.org/spotlights/esh-statement-on-covid-19/ (Accessed on March 18, 2020).
  118. International Society of Hypertension. A statement from the International Society of Hypertension on COVID-19. https://ish-world.com/news/a/A-statement-from-the-International-Society-of-Hypertension-on-COVID-19/ (Accessed on March 18, 2020).
  119. Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang (Accessed on March 18, 2020).
  120. https://hypertension.ca/wp-content/uploads/2020/03/2020-30-15-Hypertension-Canada-Statement-on-COVID-19-ACEi-ARB.pdf (Accessed on March 18, 2020).
  121. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020.
  122. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020.
  123. Wan Y, Shang J, Graham R, et al. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol 2020.
  124. Qiao Y, Shin JI, Chen TK, et al. Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate. JAMA Intern Med 2020.
  125. Joint GI society message: COVID-19 clinical insights for our community of gastroenterologists and gastroenterology care providers. https://www.gastro.org/press-release/joint-gi-society-message-covid-19-clinical-insights-for-our-community-of-gastroenterologists-and-gastroenterology-care-providers (Accessed on March 18, 2020).
  126. The European League Against Rheumatism. EULAR Guidance for patients COVID-19 outbreak. https://www.eular.org/eular_guidance_for_patients_covid19_outbreak.cfm (Accessed on March 18, 2020).
  127. The American Academy of Dermatology. https://assets.ctfassets.net/1ny4yoiyrqia/PicgNuD0IpYd9MSOwab47/023ce3cf6eb82cb304b4ad4a8ef50d56/Biologics_and_COVID-19.pdf (Accessed on March 18, 2020).
  128. American College of Rheumatology. https://www.rheumatology.org/announcements (Accessed on March 18, 2020).
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