PMC:7242012 / 115-14501 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7242012","sourcedb":"PMC","sourceid":"7242012","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7242012","text":"Watch the interview with the author\nAbbreviations\nACE2 angiotensin‐converting enzyme 2\nCDC Centers for Disease Control and Prevention\nCOVID‐19 coronavirus disease 2019\nCT computed tomography\nFDA US Food and Drug Administration\nIL‐6 interleukin‐6\nRT‐PCR reverse transcription polymerase chain reaction\nSARS severe acute respiratory syndrome\nWHO World Health Organization\nOn December 29, 2019, health authorities in China reported 27 cases of an unusual pneumonia, respiratory failure, and death linked to attendance at a live animal market in Wuhan. 1 , 2 On January 7, 2020, Chinese scientists confirmed a novel coronavirus, 2019‐nCoV, as the causative agent. 3 Studies revealed \u003e80% genetic homology of 2019‐nCoV with coronaviruses of bats, presumably the original host; pangolins, suggesting this animal sold at the market as an intermediate host; and another human coronavirus, SARS‐CoV, the cause of severe acute respiratory syndrome (SARS). 3 , 4 All evidence indicates that SARS‐CoV‐2 is of animal and not laboratory origin. 5 The World Health Organization (WHO) later named the novel virus SARS‐CoV‐2 and the related disease coronavirus disease 2019 (COVID‐19). 2 , 3 SARS‐CoV‐2 spread quickly through communities in China and other countries (Fig. 1). On January 20, 2020, the first case was recognized in the United State when a 35‐year‐old man presented to an urgent care clinic in Snohomish, Washington. 6 , 7 On January 30, 2020, WHO declared the outbreak a Public Health Emergency of International Concern. On March 11, 2020, WHO designated COVID‐19 a pandemic. Almost all countries are implementing public health measures to prevent SARS‐CoV‐2 transmission and are marshaling clinical care for patients with COVID‐19. This review highlights key features of SARS‐CoV‐2 infection, the epidemiology and clinical course of COVID‐19, and interventions to stop the growing COVID‐19 pandemic.\nFig 1 Chronology of the COVID‐19 pandemic.\n\nEpidemiology\nBy March 11, 2020, 105 countries had reported 118,319 confirmed COVID‐19 cases and 4292 deaths. 2 Outside China, large epidemics emerged in South Korea, Iran, and Italy. By March 14, 2020, approximately one in four COVID‐19 cases and deaths were in Europe. The US epidemic accelerated, with cases doubling every 6 to 7 days. 7 By March 29, 2020, more than 100,000 persons had COVID‐19 in the United States, the largest burden of COVID‐19 globally. 2 , 7 As of April 29, 2020, the COVID‐19 pandemic has grown to more than 3 million confirmed cases and more than 206,000 deaths in 179 countries. The United States now has more than 1 million cases (33%) and more than 50,000 deaths (25%). 2 , 7 The potential is high for large COVID‐19 epidemics in Brazil, Russia, India, and many African countries.\nSARS‐CoV‐2 is transmitted directly through inhalation or mucosal surface exposure to an infected person’s respiratory droplets or indirectly when touching the face after contact with contaminated objects. 2 , 4 , 7 SARS‐CoV‐2 can remain viable on environmental surfaces for up to 72 hours. 8 SARS‐CoV‐2 is highly infectious with an R0 of approximately 2.2 to 3.0, meaning each infected person will infect about two to three other persons. 7 Large COVID‐19 outbreaks have occurred in health care facilities, households, cruise ships, religious services (e.g., funerals), and other large gatherings 1 , 2 , 7 Individuals can transmit SARS‐CoV‐2 before, during, and after symptomatic disease. As many as half of individuals with SARS‐CoV‐2 infection have no symptoms. 7\n\nClinical Presentation\nSimilar to SARS‐CoV, SARS‐CoV‐2 binds to angiotensin‐converting enzyme 2 (ACE2) receptors for entry via endocytosis into alveolar epithelial cells, as well as other cells with ACE2 receptors in the heart, gastrointestinal tract, and kidneys. 2 , 4 COVID‐19 results from SARS‐CoV‐2 replication, causing early cell death (i.e., apoptosis) and provoking a storm of proinflammatory cytokines (e.g., interleukin‐6 [IL‐6]) disrupting alveolar walls with resulting fluid accumulation in alveoli. 4\nThe incubation period from infection to onset of COVID‐19 disease is typically 5 to 7 days (range 1‐14 days). 1 , 2 , 7 The most common symptoms of COVID‐19 are fever and nonproductive cough (Table 1). 1 , 4 , 7 , 9 The Centers for Disease Control and Prevention (CDC) recently added anosmia and ageusia, the loss of smell and taste, as COVID‐19 symptoms. 7 Laboratory findings are remarkable for a normal leukocyte count, lymphopenia, and elevated C‐reactive protein. 1 , 6 , 8 Most hospitalized patients with COVID‐19 have a bilateral ground‐glass appearance on chest computed tomography (CT) scan consistent with viral pneumonia.\nTable 1 Clinical Features of COVID‐19 in Wuhan and Multiple Other Locations in China\nClinical Features Wuhan, China Multiple Locations, China\nNumber of patients 10,999 3,062\nSymptoms\nFever 89% 80%\nCough 68% 63%\nExpectoration 34% 42%\nDyspnea 19% 34%\nFatigue/Myalgia 38% 46%\nHeadache 14% 15%\nNausea/Vomiting 5% 10%\nDiarrhea 4% 13%\nLaboratory results\nLeukocytes in normal range 94% 70%\nLymphopenia 83% 57%\nIncreased C‐reactive protein 61% 74%\nAlanine aminotransferase above upper limit of normal 21% 29%\nImaging\nAbnormal chest CT 86% 89%\nBilateral infiltrates (ground glass) 56% 76%\nAcute respiratory distress syndrome 6% 20%\nMortality 1.4% 6%\nData are from Guna et al. 1 and Centers for Disease Control and Prevention. 7\nJohn Wiley \u0026 Sons, Ltd This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency. Today, reverse transcription polymerase chain reaction (RT‐PCR) is the COVID‐19 diagnostic test. 2 , 7 RT‐PCR sensitivity is highest for testing bronchial alveolar lavage fluid (93%) and declines for sputum (72%) and nasal swab (63%) specimens. 10 COVID‐19 diagnosis might require repeat testing. 2 , 7 Serological tests to detect SARS‐CoV‐2 IgM and IgG antibodies are available. However, because of test sensitivity and other quality concerns, the US Food and Drug Administration (FDA; https://www.fda.gov) advises current serological tests are best used for surveillance and research, and not as the sole basis for COVID‐19 diagnosis.\nCOVID‐19 is commonly a mild disease. Of the first 72,314 COVID‐19 disease reported in China, 81% had no or mild pneumonia, 21% had severe dyspnea and radiological evidence of pulmonary disease, and 5% progressed to SARS. 1 Individuals can be ill for a week or longer before experiencing severe symptoms.\nThe risk for severe COVID‐19 disease is highest for men, older adults, and patients with certain comorbidities. In the United States, 80% of reported COVID‐19–related deaths are among people aged ≥65 years. 7 , 9 , 11 Deaths are rare among persons \u003c24 years of age. 1 , 7 , 11 In the United States, most hospitalized patients with COVID‐19 have comorbid conditions, including obesity, hypertension, diabetes, and cardiovascular disease 7 , 11 (Table 2). Although listed by the CDC as a comorbid condition associated with severe COVID‐19, chronic liver disease, including cirrhosis, has not been a common comorbidity associated with hospitalization in the United States (Table 2). The high prevalence of comorbid conditions can explain, in part, African Americans’ increased risk for hospitalization with COVID‐19 disease. 5 Variable comorbidity prevalence contributes to differences in national COVID mortality. Globally, crude fatality rates for COVID‐19 range from 0.2% in Singapore, to 2.0% to 3.0% in South Korea and Germany, to 4.3% for the United States, and to 10% to 13% in Spain, Italy, and the United Kingdom. 2 , 5\nTable 2 Comorbidities Among Persons With COVID‐19 Disease, United States\nCondition United States* New York City\nNot Hospitalized Hospitalized Intensive Care Hospitalized\nPatients 5143 1037 457 5700\nOne or more condition 27% 71% 78% 88%\nObesity 42%\nHypertension 57%\nDiabetes mellitus 6% 24% 32% 34%\nCardiovascular disease 5% 23% 29% 18%\nChronic renal disease 1% 9% 12% 0.6%\nChronic liver disease 1% 1% 2% 9%\nImmunocompromised 3% 6% 9% 2%\nMortality 21%\nTotal 21%\n1 Comorbidity 88%\n* Based on data from the CDC for all 50 states and territories. Otherwise, data are Richardson et al. 11\nJohn Wiley \u0026 Sons, Ltd This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency. The search for effective therapies and a vaccine is occurring at a remarkable pace, with at least 29 studies of therapeutic agents and 5 studies of candidate vaccines registered on ClinicalTrials.org (https://www.clinicaltrials.gov). On May 1, 2020, the FDA granted Emergency Use Authorization of remdesivir, a broad‐spectrum antiviral nucleotide prodrug for treatment of severe COVID‐19. Studies of monoclonal antibodies against IL‐6 and hyperimmune immunoglobulin are in progress. Following reports of serious cardiac arrythmias, the FDA cautioned clinicians of prescribing hydroxychloroquine or chloroquine for treatment of COVID‐19. A safe and effective vaccine, if successfully developed, probably will not be available for 12 to 18 months.\n\nPrevention\nIn the absence of a vaccine, prevention is composed of a combination of nonpharmacological interventions for suppression of transmission to R0 \u003c1 and mitigation of the number of patients with COVID‐19 who require intensive care and mechanical respiratory support. 12 Interventions include improved personal hygiene promotions, symptomatic screening and laboratory testing for case detection, contact tracing, household quarantine of those with transmission risks, and social distancing (Table 3). The United States and most other countries have implemented extensive travel restrictions, workplace and school closures, and cancellation of sporting and other large public events. China, South Korea, and Taiwan successfully curbed large COVID‐19 epidemics with prompt scale‐up of testing, contact tracing, and quarantine. 2 , 4 , 7 In the United States, although testing rates are low, models suggest prevention measures are reducing transmission and future deaths. 13 The US government recently recommended increased COVID‐19 surveillance, testing, and contact tracing with modified social distancing measures to sustain SARS‐CoV‐2 prevention while opening up education and commerce. 14\nTable 3 Prevention Measures to Reduce Risks for COVID‐19, Priority Populations for Testing, and Information Resources\nPrevention measures to reduce risks for COVID‐19 Practice good hygiene\n○ Wash hands often for \u003e20 seconds with soap and water or 60% alcohol sanitizer\n○ Avoid touching eyes, nose, and mouth with unwashed hands\n○ Sneeze or cough into a tissue or inside of the elbow\n○ Disinfect surfaces and used items frequently with soap and water and Environmental Protection Agency–registered household disinfectants or bleach solution (4 teaspoons [20 mL] bleach per quart [or 1 L] water)\nLimit close social contact\n○ Learn signs and symptoms of COVID‐19, and follow local disease trends\n○ Stay home as much as possible, particularly persons who are ill, older (\u003e65 years) adults, and those at risk for severe COVID‐19\n○ Persons who are ill, call a health care provider\n○ Consider 2‐week supply of medications, food, and other essentials\n○ When out in public, keep social distance of at least 6 feet and wear a cloth face cover\n○ Avoid gatherings of \u003e10 persons\n○ Work or attend school from home\n○ Avoid unnecessary travel\n○ Avoid visits to nursing homes or long‐term retirement facilities\nProtect patients and health care workers\n○ Reduce facility risks: screen for COVID‐19 symptoms on entry; reduce visits; practice telemedicine\n○ Isolate symptomatic patients as soon as possible\n○ Protect health care personnel with recommended infection‐control procedures\nRecommended testing in consultation with health care provider Hospitalized patients\nPersons with symptoms of COVID‐19\n○ Health care facility workers\n○ Patients in long‐term care facilities\n○ Patients \u003e65 years of age\n○ Patients with underlying conditions with symptoms\n○ First responders\nCritical infrastructure workers and others with symptoms\nHealth care facility workers and first responders\nPersons mildly ill in communities with high numbers of COVID‐19 hospitalizations\nGood information resources Centers for Disease Control and Prevention: https://www.cdc.gov/coronavirus/2019-ncov/index.html\nWorld Health Organization: https://www.who.int/emergencies/diseases/novel-coronavirus-2019\nInfectious Disease Society of America: https://www.idsociety.org/public-health/COVID-19-Resource-Center/\nAmerican Association for the Study of Liver Diseases: https://www.aasld.org/about-aasld/covid-19-resources\nEuropean Association for the Study of the Liver: https://easl.eu/covid-19-and-the-liver/\nEuropean Centre for Disease Control and Prevention: https://www.ecdc.europa.eu/en/covid-19-pandemic\nThe Society for Healthcare Epidemiology of America: https://www.shea-online.org/\nJohn Wiley \u0026 Sons, Ltd This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.\n\nSummary\nSARS‐CoV‐2 is a new human pathogen, readily spread via respiratory droplets and the cause of the growing COVID‐19 pandemic. Men, older adults (\u003e65 years old), and persons with comorbidities are at risk for severe COVID‐19 and death. Countries have successfully suppressed transmission and mitigated needs for intensive care with robust case/contact detection (testing), isolation of infected/exposed persons, and social distancing. To stop the COVID‐19 pandemic, the challenge is for all countries to scale up and sustain prevention measures while awaiting the arrival of effective vaccines and 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