Coronavirus Disease 2019 (COVID-19)

Updated: Apr 04, 2020
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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Overview

Practice Essentials

Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV), which was first identified amid an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China. [1] It was initially reported to the WHO on December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global health emergency. [2, 3] On March 11, 2020, the WHO declared COVID-19 a global pandemic, its first such designation since declaring H1N1 influenza a pandemic in 2009. [4]

Illness caused by SARS-CoV-2 was recently termed COVID-19 by the WHO, the new acronym derived from "coronavirus disease 2019." The name was chosen to avoid stigmatizing the virus's origins in terms of populations, geography, or animal associations. [5, 6] On February 11, 2020, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses issued a statement announcing an official designation for the novel virus: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [7]

The Centers for Disease Control and Prevention (CDC) has stated that more cases of COVID-19 are likely to be confirmed in the United States in the near future. They also anticipate widespread SARS-CoV-2 community spread and that most of the US population will be exposed to the virus in coming months, leading to a CDC recommendation against gatherings of 10 persons or more.

The CDC has postulated that this situation could result in large numbers of patients requiring medical care concurrently, resulting in overloaded public health and healthcare systems and, potentially, elevated rates of hospitalizations and deaths. The CDC advises that nonpharmaceutical interventions (NPIs) will serve as the most important response strategy in attempting to delay viral spread and to reduce disease impact. [8]

The feasibility and implications of strategies for suppression and mitigation have been rigorously analyzed and are being encouraged or enforced by many governments in order to slow or halt viral transmission. Population-wide social distancing of the entire population plus other interventions (eg, home self-isolation, school and business closures) is strongly advised. These policies may be required for long periods to avoid rebound viral transmission. [9]

According to the CDC, individuals at high risk of infection include persons in areas with ongoing local transmission, healthcare workers caring for patients with COVID-19, close contacts of infected persons, and travelers returning from locations where local spread has been reported. [8]

Person-to-person spread of SARS-CoV-2 has been reported in the United States. [10, 11] Individuals who believe they may have been exposed to SARS-CoV-2 should immediately contact their healthcare provider.

The CDC has also provided recommendations for individuals who are at high risk of COVID-19–related complications, including older adults and persons who have serious underlying health conditions (eg, heart disease, diabetes, lung disease). Such individuals should consider the following precautions: [12]

  • Stock up on supplies.
  • Avoid close contact with sick people.
  • Wash hands often.
  • Stay home as much as possible in locations where COVID-19 is spreading.
  • Develop a plan in case of illness.

Healthcare personnel are also referred to Medscape’s Novel Coronavirus Resource Center for the latest news, perspective, and resources.

Signs and symptoms

Presentations of COVID-19 have ranged from asymptomatic/mild symptoms to severe illness and mortality. Symptoms may develop 2 days to 2 weeks following exposure to the virus. [13] A pooled analysis of 181 confirmed cases of COVID-19 outside Wuhan, China, found the mean incubation period to be 5.1 days and that 97.5% of individuals who developed symptoms did so within 11.5 days of infection. [14]

Wu and McGoogan reported that, among 72,314 COVID-19 cases reported to the Chinese Center for disease Control and Prevention (CCDC), 81% were mild (absent or mild pneumonia), 14% were severe (hypoxia, dyspnea, >50% lung involvement within 24-48 hours), 5% were critical (shock, respiratory failure, multiorgan dysfunction), and 2.3% were fatal. [15]

Common symptoms have included the following:

  • Fever
  • Cough
  • Myalgia
  • Fatigue

Less-common symptoms have included the following:

  • Headache
  • Sputum production
  • Diarrhea
  • Malaise
  • Shortness of breath/dyspnea
  • Respiratory distress

The most common serious manifestation of COVID-19 appears to be pneumonia.

A complete or partial loss of the sense of smell (anosmia) has been reported as a potential history finding in patients eventually diagnosed with COVID-19, but this has not been a distinguishing feature in published studies, so its clinical importance is questionable. [16]

Symptoms in children with infection appear to be uncommon, although some children with severe COVID-19 have been reported. [15, 17, 18]

See Clinical Presentation.

Diagnosis

COVID-19 should be considered a possibility in (1) patients with respiratory tract symptoms and newly onset fever or (2) in patients with severe lower respiratory tract symptoms with no clear cause. Suspicion is increased if such patients have been in an area with community transmission of SARS-CoV-2 or have been in close contact with an individual with confirmed or suspected COVID-19 in the preceding 14 days.

Microbiologic testing is required for definitive diagnosis. At present, such testing is of limited availability.

Patients who do not require emergency care are encouraged to contact their healthcare provider over the phone. Patients with suspected COVID-19 who present to a healthcare facility should prompt infection-control measures. They should be evaluated in a private room with the door closed (an airborne infection isolation room is ideal) and asked to wear a surgical mask. All other standard contact and airborne precautions should be observed, and treating healthcare personnel should wear eye protection. [19]

See Workup.

Management

No specific antiviral treatment is recommended for COVID-19. Infected patients should receive supportive care to help alleviate symptoms. Vital organ function should be supported in severe cases. [20]

No vaccine is currently available for SARS-CoV-2. Avoidance is the principal method of deterrence.

Numerous collaborative efforts to discover and evaluate effectiveness of antivirals (eg, remdesivir), immunotherapies (eg, hydroxychloroquine, sarilumab), monoclonal antibodies, and vaccines have rapidly emerged.

For more information on investigational drugs and biologics being evaluated for COVID-19, see Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies.

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Background

Coronaviruses comprise a vast family of viruses, 7 of which are known to cause disease in humans. Some coronaviruses that typically infect animals have been known to evolve to infect humans. SARS-CoV-2 is likely one such virus, postulated to have originated in a large animal and seafood market. Recent cases involve individuals who reported no contact with animal markets, suggesting that the virus is now spreading from person to person. [21]

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are also caused by coronaviruses that “jumped” from animals to humans. More than 8,000 individuals developed SARS, nearly 800 of whom died of the illness (mortality rate of approximately 10%), before it was controlled in 2003. [22] MERS continues to resurface in sporadic cases. A total of 2,465 laboratory-confirmed cases of MERS have been reported since 2012, resulting in 850 deaths (mortality rate of 34.5%). [23]

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Route of Transmission

Transmission is believed to occur via respiratory droplets from coughing and sneezing, as with other respiratory pathogens, including influenza and rhinovirus. [24] Virus released in respiratory secretions can infect other individuals via direct contact with mucous membranes. Droplets usually cannot travel more than 6 feet. The virus can also persist on surfaces to varying durations and degrees of infectivity. One study found that SARS-CoV-2 remained detectable for up to 72 hours some surfaces despite decreasing infectivity over time. Notably, the study reported that no viable SARS-CoV-2 was measured after 4 hours on copper or after 24 hours on cardboard. [25]

The duration of viral shedding varies significantly and may depend on severity. Among 137 survivors of COVID-19, viral shedding based on testing of oropharyngeal samples ranged from 8-37 days, with a median of 20 days. [26] A different study found that repeated viral RNA tests using nasopharyngeal swabs were negative in 90% of cases among 21 patients with mild illness, whereas results were positive for longer durations in patients with severe COVID-19. [27]

Data have suggested that asymptomatic patients are still able to transmit infection. This raises concerns for the effectiveness of isolation. [28, 29] Zou et al followed viral expression through infection via nasal and throat swabs in a small cohort of patients. They found increases in viral loads at the time that the patients became symptomatic. One patient never developed symptoms but was shedding virus beginning at day 7 after presumed infection. [30]

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Epidemiology

Coronavirus outbreak and pandemic

As of April 4, 2020, COVID-19 has been confirmed in more than one million individuals worldwide and has resulted in more than 60,000 deaths. More than 180 countries have reported laboratory-confirmed cases of COVID-19 on all continents except Antarctica. [31]

In the United States, 278,458 cases of COVID-19 have been confirmed as of April 4, 2020, resulting in 7,159 deaths. [32, 33] As of March 26, 2020, the United States has more confirmed infections than any other country in the world, including China and Italy. [34]

Current clusters of increased local transmission can be found throughout Western Europe, the United States, and Iran. The rate of newly reported infections in China has dropped precipitously.

An interactive map of confirmed cases can be found here.

United States data

In the United States, attributable deaths have been most common in adults aged 85 years or older (10%-27%), followed by adults aged 65-84 years (3%-11%), adults aged 55-64 years (1%-3%), and adults aged 20-54 years (< 1%). As of March 16, 2020, no attributable fatalities had been reported in persons aged 19 years or younger. [35]

In the United States, as of March 16, 2020, patients aged 65 years or older had accounted for 31% of all reported COVID-19 cases, 45% of hospitalizations, 53% of admissions to the ICU, and 80% of fatalities attributable to the infection. [35]

Among 2,449 reported cases of COVID-19 in the United States as of March 16, 2020, in which age was known, 6% of patients were aged 85 years or older, 25% were aged 65-84 years, 18% were aged 55-64 years, 18% were aged 45-54 years, 29% were aged 20-44 years, and 5% were aged 19 years or younger. [35]

Among 508 hospitalized US patients as of March 16, 2020, 9% of patients were aged 85 years or older, 26% were aged 65-84 years, 17% were aged 55-64 years, 18% were aged 45-54 years, 20% were aged 20-44 years, and persons aged 19 years or younger accounted for less than 1%. [35]

Among US patients admitted to the ICU as of March 16, 2020, 7% were adults aged 85 years or older, 46% were aged 65-84 years, 36% were aged 45-64 years, and 12% were aged 20-44 years. No persons aged 19 years or younger have been admitted to the ICU. [35]

On February 26, 2020, the first case of COVID-19 not associated with travel from China or known contact with an infected traveler was reported in California. [36] Community spread of the virus has now been reported in multiple states. [8]

COVID-19 in China

COVID-19–related deaths in China have mostly involved older individuals (≥60 years) and persons with serious underlying health conditions. [35]

An initial report of 425 patients with confirmed COVID-19 in Wuhan, China, attempted to describe the epidemiology. Many of the initial cases were associated with direct exposure to live markets, while subsequent cases were not. This further strengthened the case for human-to-human transmission. The incubation time for new infections was found to be 5.2 days, with a range of 4.1-7 days. The longest time from infection to symptoms seemed to be 12.5 days. At this point, the epidemic had been doubling approximately every 7 days, and the base reproductive number was 2.2 (meaning every patient infects an average of 2.2 others). [37] Further data will likely better define the clinical course, incubation time, and duration of infectivity.

On March 10, 2020, Dr. Zunyou Wu of the CCDC delivered a report at the Conference on Retroviruses and Opportunistic Infections (CROI) meeting detailing data from China, including updates on epidemiology and clinical presentation. COVID-19 was reported to be most severe in older adults, but a marked male predominance was no longer found. At presentation, approximately 40% of the cases were “mild” with no pneumonia symptoms. Another 40% were “moderate” with symptoms of viral pneumonia, 15% were severe, and 5% critical. During the course of the illness, 10%-12% of cases that initially presented as mild or moderate illness progressed to severe, and 15%-20% of severe cases eventually became critical. The mean time from exposure to symptoms was 5-6 days. Patients with mild cases seem to recover within 2 weeks, while patients with severe infections may take 3-6 weeks to recover. Deaths were observed from 2-8 weeks following symptom onset. Interestingly, completely asymptomatic infection was rare (< 1%) after detailed symptom assessments. Analysis of the virology data does suggest that patients can shed virus 1-2 days before symptoms appear, raising concern for asymptomatic spread.

In an initial report of 41 patients infected in Wuhan, China, Huang et al reported a 78% male predominance, with 32% of all patients reporting underlying disease. [38]

COVID-19 in children

To date, multiple outbreak reports have noted the relative sparing of the pediatric population, especially from severe disease. While case reports (and recently a news report from Chicago) have described severe disease in children, these have been rare and often associated with comorbidities.

In the largest case series, Dong et al presented data on 2,143 children younger than 18 years infected in Wuhan, China, between January 16 and February 8, 2020. The median age was 7 years, (interquartile range [IQR], 2-13 years) and 56.6% were male. Less than 10% were severe or critical cases. Younger age (especially infancy) increased the risk of severe illness. The proportion of severe and critical cases was 10.6% for children younger than 1 year, 7.3% for children aged 1-5 years, 4.2% for children aged 6-10 years, 4.1% for children aged 11-15 years, and 3% for children aged 16 years or older. [17]

Similarly, Qiu and colleagues retrospectively analyzed data from patients with COVID-19 (n=36) younger than 17 years (mean age, 8.3 [SD, 3.5] years) in Zhejiang, China, from January 17 to March 1, 2020. Most children were believed to be infected via close contact with family members. Clinically, 19 (53%) patients had a moderate presentation with pneumonia; 7 (19%) had a mild presentation with upper respiratory infection, and 10 (28%) were asymptomatic. Common symptoms upon admission included fever (13 [36%]) and dry cough (7 [19%]). The authors raised concerns about the large number of asymptomatic infections being a reservoir of transmission. [18]

Similar outcomes were noted by Jiehao et al. [39]

An Expert Consensus Statement has been published that discusses diagnosis, treatment, and prevention of COVID-19 in children.

COVID-19 in pregnant women and neonates

Zhu et al analyzed the outcomes of 10 neonates born to mothers with confirmed COVID-19. [40] Of the 9 mothers (one gave birth to twins), 4 were symptomatic prior to delivery, 2 became symptomatic at delivery, and 3 developed symptoms in the postpartum period. Nine of the 10 neonates tested negative for COVID-19 from 1-9 days following delivery. One mother died, 5 were discharged, and 4 were hospitalized. The infants most commonly experienced respiratory distress, but abnormal liver function and thrombocytopenia aware also observed. Premature birth was observed in 6 women, consistent with a case report by Wang et al. [41]

Zeng et al presented data on 33 neonates born to mothers with COVID-19. [42] They reported good outcomes overall but drew attention to three newborns with COVID-19, all of whom presented with early-onset pneumonia but eventually recovered. The authors note that each was delivered via cesarean delivery while infection-control precautions were observed to minimize the risk of transmission. Therefore, they raise the possibility of vertical infection. This is in contrast to data analyzed by Schwartz et al, finding no instances of vertical transmission in 38 pregnant women with COVID-19. [43]

Chen et al reported data on 9 pregnant women with COVID-19 with live births delivered via cesarean delivery in Wuhan, China. [44] Seven of the 9 women presented with a fever; other symptoms included cough (4 of 9 patients), myalgia (3), sore throat (2), and malaise (2). Five of nine patients had lymphopenia (< 1.0 × 109 cells/L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died as of Feb 4, 2020. Among the 9 neonates, 2 were reported to have fetal distress. All fared well, with excellent Apgar scores. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from 6 of the neonates were tested for SARS-CoV-2, all with negative results.

Yu and colleagues presented data on 7 pregnant patients with COVID-19. The mean age was 32 years (range, 29-34 years), and the mean gestational age was 39 weeks plus 1 day (range, 37 weeks to 41 weeks plus 2 days). They observed fever in 86% of the women, cough in 14%, shortness of breath in 14%, and diarrhea in 14%. All underwent cesarean delivery within 3 days of clinical presentation, with an average gestational age of 39 weeks plus 2 days, with good outcomes. Three neonates were tested for SARS-CoV-2, and one neonate was infected with SARS-CoV-2 36 hours after birth. [45]

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Prognosis

Early reports have described COVID-19 as clinically milder than MERS or SARS in terms of severity and case fatality rate. [23] Thus far, the fatality rate for COVID-19 appears to be around 2%. [33]

Early in the outbreak, the WHO reported that severe cases in China had mostly been reported in adults older than 40 years with significant comorbidities and skewed toward men, although this pattern may be changing. [33]

COVID-19–related deaths in China have mostly involved older individuals (≥60 years) and persons with serious underlying health conditions. In the United States, attributable deaths have been most common in adults aged 85 years or older (10%-27%), followed by adults aged 65-84 years (3%-11%), adults aged 55-64 years (1%-3%), and adults aged 20-54 years (< 1%). As of March 16, 2020 no fatalities or ICU admissions had been reported in persons aged 19 years or younger. [35]

In China, the case-fatality rate was found to range from 5.8% in Wuhan to 0.7% in the rest of China. [46] In most cases, fatality occurs in patients who are older or who have underlying health conditions (eg, diabetes, cardiovascular disease, chronic pulmonary disease, cancer, hypertension). [47]

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Virology

The full genome of SARS-CoV-2 was first posted by Chinese health authorities soon after the initial detection, facilitating viral characterization and diagnosis. [8] The CDC analyzed the genome from the first US patient who developed the infection on January 24, 2020, concluding that the sequence is nearly identical to the sequences reported by China. [8] SARS-CoV-2 is a group 2b beta-coronavirus that has at least 70% similarity in genetic sequence to SARS-CoV. [23] Like MERS-CoV and SARS-CoV, SARS-CoV-2 originated in bats. [8]

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