Coronaviruses are enveloped RNA viruses, characterized by surface protein spikes, which, under electron microscopy, resemble the sun’s corona. Numerous coronaviruses, first discovered in domestic poultry in the 1930’s, cause respiratory, gastrointestinal, liver, and neurologic diseases in animals.
Human Coronavirus Infection (HCoV)
Only 7 coronaviruses cause disease in humans (HCoV).
Four of the 7 HCoV (HCoV-NL63, -229E, -OC43, and -HKU1) cause mild and self-limiting upper respiratory tract infections, such as the common cold, but can cause severe lower respiratory tract infections, including pneumonia, in infants, the elderly, and the immunocompromised. These HCoV infections show a seasonal pattern with most cases occurring in the winter months in temperate climates.
Three of the 7 HCoV (SARS-CoV, MERS-CoV, and SARS-CoV2) have caused major outbreaks of deadly pneumonia in the 21st century.
The first of these outbreaks, severe acute respiratory syndrome (SARS), first emerged in November 2002 in Guangdong province in southern China and caused an epidemic that spread within months to 29 countries and 6 continents. It sickened over 8,000 people and killed almost 800 worldwide. The majority of cases occurred in China and Hong Kong. In the United States, only 8 people had laboratory-confirmed SARS; all 8 had traveled to areas where SARS-CoV transmission was occurring. The overall case fatality rate was 10%, but varied by age, ranging from < 1% in people aged 24 years and younger to > 50% in those aged 65 years and older.
The source of SARS was palm civets (cat-like mammals) that had been sold as food at local live animal markets in Guangdong. Once introduced into humans, SARS-CoV readily spread person-to-person by large respiratory droplets, aerosols, and by fecal-oral transmission (diarrhea is a common manifestation of the infection).
The next HCoV to cause deadly infection was Middle East Respiratory Syndrome coronavirus (MERS-CoV), which emerged in the Arabian Peninsula in September 2012. MERS-CoV has caused recurrent outbreaks that have sickened over 2,500 people with a case fatality rate of about 35%. Most infected people lived in or recently traveled from the Arabian Peninsula. 85% of cases were reported from Saudi Arabia. The largest MERS outbreak outside the Arabian Peninsula occurred in South Korea in 2015, associated with a traveler returning from the Arabian Peninsula.
MERS-CoV, like SARS-CoV, is a zoonosis, spread by direct or indirect contact with dromedary camels. MERS-CoV also spreads human to human by direct contact, fomites, and respiratory droplets. 42% of all cases in 2018-2019 were linked to clusters of human-to-human transmission in households or healthcare facilities. The source was unknown for 60%. MERS-CoV virus is detected respiratory tract secretions, feces, serum, and urine, and virus has been detected in survivors for a month or more after onset.
The seventh HCoV to be discovered is SARS-CoV2, the cause of an outbreak, named COVID-19, that is currently spreading worldwide. The outbreak began in Wuhan, a city of over 11 million, in Hubei Province, Central China. (Wuhan is home to the Wuhan Institute of Virology, a leading center for coronavirus research, although no connection is suspected between the research and the current outbreak.) SARS-CoV-2 is most closely related, with 96% genetic similarity, to a coronavirus isolated from horseshoe bats that were found in caves in Yunnan, China, over 1000 km (about 621 miles) from Wuhan (1).
Similar to the events in the 2002–2003 SARS epidemic, early reports suggested that SARS-CoV-2 had jumped from animals to humans at Wuhan's Huanan Seafood Wholesale Market, where many different species of live animals were clustered in cages, offering opportunities for viral transmission. As a result, the Wuhan market was closed on Jan. 1, 2020, but evidence now suggests this market was not the source of the outbreak. Only the third of the first five human cases with confirmed SARS-CoV-2 infection in Wuhan had any link to the Wuhan market (2) and, although environmental samples from the site in the market where wildlife was sold were positive for SARS-CoV-2, tissue samples from the market's animals were negative for the virus. How this virus thus made the jump from Yunnan bats to human beings remains unknown.
By the first of this year, there were 41 cases in Wuhan. A week later, Chinese investigators reported that they identified the cause was a new coronavirus and its genetic sequence was published on an open-access database. On Jan 18, when the case count had risen to almost 200, more than 10,000 families in Wuhan attended an annual banquet to celebrate the Lunar New Year. Days later, on the eve of Lunar New Year when many people travel to their home towns for family reunions, Chinese authorities responded to increasing case counts by locking down millions of people living in Hubei Province.
The borders of Wuhan were blocked — allowing no one in or out. People were required to remain in their apartments, increasing the physical distance between people outside of households. Schools and universities closed. All types of recreational venues and most public places closed. Only essential businesses were allowed to remain open. However, an estimated five million people had left Wuhan before the lockdown began and consequently the number of cases surged in the surrounding Chinese provinces. By early February, the virus had spread to all provinces of mainland China (37,000 cases) and cases with a history of travel from Wuhan also began appearing outside China, in places such as Hong Kong and Singapore, and the West Coast of the US.
Despite the lockdown in Hubei, by early February, the confirmed case count in Hubei was about 25,000 and a month later, 64,000. After 9 weeks of sustained transmission, Hubei Province reported 64,084 confirmed cases with 2,346 deaths. The actual number of cases was probably much higher as only the most severe cases were likely included in reports due to shortages of testing kits. The presence of many undiagnosed mild infections probably limited efforts to control further spread of this infection. The rapidity of spread is high with a reported R0 of 5.7 (range, 3.8-8.9), when compared to the 2003 SARS outbreak with an R0 of 2-3, suggesting SARS-CoV2 is much more transmissible than SARS-CoV (3). To explain its greater transmissibility, SARS-CoV-2 is most contagious in the several days before an infected person becomes symptomatic (unlike SARS-CoV, which is most contagious at the time symptoms begin), permitting unwitting spread of the infection by asymptomatic individuals. SARS-CoV-2 also has a much higher affinity for the angiotensin-converting enzyme 2 (ACE2) host cell surface receptor on the nasal epithelium than the 2003 SARS virus (4), perhaps providing a molecular basis for the greater contagiousness of SARS-CoV-2.
By early February 2020, the Hubei lockdown began to show an effect; the rate of increase in the daily new case counts first began to slow and then the number of new cases each day began falling in mid-February. On March 8, for the first time since mid-January the number of newly reported cases in a 24-hour period was less than 50 and a week later there were no new locally acquired cases in Hubei province. In mid-March, the lockdown in Hubei was gradually lifted and new case counts have remained low. China, the world’s most populous country and the original epicenter of the COVID-19 outbreak, was able to reduce transmission to a manageable level. Currently, most new infections in China are imported from outside the country and community spread is being limited by isolating cases, tracing contacts, and quarantining contacts.
On March 11, 2020, when community spread was occurring in multiple locations throughout the world and 36 % of the total number of COVID-19 cases were being reported outside mainland China, WHO declared COVID-19 was pandemic. By then the outbreak in China had subsided and Western Europe, mainly Italy, Spain, Germany, France, and the UK, had become the new hotspots. The rapid rise in the number of new cases each day in these European countries prompted lockdowns and within the next 14 days (one incubation period for COVID-19), the daily new case counts, after peaking, began dropping. As in Hubei, the impact of lockdowns was seen only when at least one incubation period had passed, allowing for manifestation of symptoms in newly infected individuals who were still in their incubation period at the start of the lockdown.
The next hotspot was in mid-March in the northeastern region of the US. With rapidly rising daily case counts, New York, New Jersey, Connecticut, and Massachusetts imposed statewide stay-at-home orders and closure of all non-essential businesses on or about March 22, 2020. The daily new case counts continued to increase, peaking in the first week of April, and then falling during the next 14 days, to reach stable lower levels of fewer than 1000 newly infected cases daily in mid-June, a pattern similar to the response to lockdowns in China and Europe. Nevertheless, if New York, the state with most confirmed cases were considered a country, the state’s current total case count of over 430,000 cases would be the 5th largest, after the US as a whole (3.6 million), Brazil (almost 2 million), India (almost 1 million), and Russia (almost 750,000). More than half of the state's cases were in New York City, where nearly half the state's population lives.
These 4 northeastern US states have not seen a second spike in the daily new case counts and the number of deaths has remained stable, despite gradual easing of lockdowns. Their successful response resembles the success of China and the European countries in bringing the pandemic under control. This is in sharp contrast to many other US states, especially in the south and southwest regions, where the new cases counts each day either have spiked after an initial decline or just continued to climb (currently over 12,000 new cases in a day in Texas and over 15,000 in Florida) , exceeding the highest daily new case count in New York State. This is likely the result of the inability of the population in these states to practice physical distancing and use face masks.
Although the rise in new case counts could partially be due to increased testing, COVID-19 hospitalizations and deaths, indicators not influenced by increased testing, are also rapidly rising in these states. Also, the frequency of positive PCR tests is rising faster than the increase in testing in these states (5). The number of new cases for the US as a whole occurring each day is now above 70,000, which is approaching the total number of cases of COVID-19 in China over the past 8 months (about 83,000).
To control recurrent local outbreaks, some countries, such as China, Singapore, Spain, Australia, and Germany, have reintroduced regional lockdowns, which is likely what will be necessary in the US (6). Lockdowns have had proven efficacy. Once community spread has been greatly lessened, lockdowns can then be gradually eased in conjunction with containment procedures that involve testing, isolating cases, and promptly tracing and quarantining their contacts. Countries will still face reintroductions from endemic regions outside their borders, as has happened in China and South Korea, so containment strategies must be ongoing.
Resurgence of COVID-19 after relaxation of lockdown measures has occurred in countries that have previously controlled their outbreaks. These outbreaks have often been characterized by a large number of people who attended a particular event, where transmission was heighten by closed indoor spaces, crowded settings, and close contacts with others without use of any personal protection like face masks. For example, more than 100 cases were linked to nightlife venues in the Seoul, South Korea, after lockdown measures were eased. Bars and night clubs where the combination of alcohol intoxication, crowding, people not wearing face masks trying to talk above each other and over loud music are typical high-risk settings. Shouting propels viral loaded respiratory droplets further. Air conditioners may contribute to spread, potentially blowing respiratory droplets along the path of the air conditioner’s airflow. An additional factor is likely the use of public restrooms, with high-touch surfaces contaminated by unwashed hands, coupled with aerosols generated by flushing lid-free toilets with SARS-CoV-2-contaminated feces.
Transmission of SARS-CoV2
SARS-CoV2 is thought to spread mainly by
- Inhalation of large respiratory droplets containing live virus sprayed within a 1-meter radius of a coughing or sneezing infected person
Other modes of transmission include
- Inhaling small airborne respiratory emissions containing the virus
- Touching virus-contaminated surfaces and then touching the eyes, nose or mouth
- Possibly fecal-oral transmission
Superspreaders played an extraordinary role in driving the 2003 SARS outbreak and are likely playing a significant role in the current COVID-19 outbreak. A super-spreader is an individual who transmits an infection to a significantly greater number of other people than the average infected person. Multiple factors contribute to superspreading, including host behavior that increases the number and length of contacts with susceptible individuals, crowding, poor ventilation, improper isolation procedures, unnecessary movement of infectious individuals, misdiagnosis, virulence and viral load, and co-infection with another pathogen.
One COVID-19 superspreader, a British businessman, contracted SARS-CoV2 at a conference in Singapore on Jan 20-22, 2020 that was attended by 109 people from many different countries, at least one of whom was from Hubei, before traveling to France, where he spread the disease to 11 fellow guests at a ski chalet in the French Alps. He then flew home to the United Kingdom via Switzerland before discovering he harbored SARS-CoV2. Six others who attended the Grand Hyatt conference also developed COVID-19: a Malaysian, two South Koreans, and three Singaporeans.
The most important preventive measure is avoidance of exposure to SARS-CoV2 by means of
- Respiratory and contact precautions
Respiratory precautions involve using face masks. Two types of face masks are available, surgical (whether medical products or other cloth masks) and N-95. Patients should wear a surgical mask, which helps contain their respiratory secretions, thus protecting others. However, surgical masks do not fit tightly enough to definitively protect uninfected people from inhaling infected respiratory emissions (although they may limit transfer of virus from hands to nose and mouth). Thus, people in contact with infected patients (eg, health care providers, household members) should wear N-95 masks, which fit very tightly, and protect the wearer from airborne respiratory emissions.
Contact precautions include
- Avoiding close contact with people having COVID-19
- Avoiding touching one’s eyes, nose, and mouth with unwashed hands
- Washing hands often with soap and water for at least 20 seconds or using an alcohol-based hand sanitizer that contains at least 60% alcohol if soap and water are not available.
Environmental surfaces that are frequently touched by multiple people (eg, doorknobs, bathroom fixtures, keyboards elevator buttons) should be cleaned using disposable wipes before each use.
Quarantine is essential. For patients, illness severity helps determine whether they are isolated in a hospital or at home. Well individuals who had close contact with a COVID-19-infected patient are quarantined at home for the duration of the incubation period, ie, 14 days after the last exposure.
Indoor restaurants and large parties or social gatherings at people's homes where people will be eating, drinking, and talking to each other in close proximity not wearing face mask, as well as indoor sporting events where people are cheering and shouting are high-risk venues for a “superspreader” event in which a single or a few infected people can trigger a large outbreak. Recommendations are that such events where large numbers of people can be exposed in a high-risk setting, such as such as nightclubs and bars, festivals, conferences, and sporting events be postponed until the level of community transmission is low, especially for people with a higher risk of developing severe cases of COVID-19 (7).
1. Zhou P, Yang XL, Wang XG, et al: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579: 270-273, 2020.
2. Li Q, Guan X, Wu P, et al: Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 382: 1199-1207, 2020 Epub 29 Jan. 2020. doi: 10.1056/NEJMoa2001316
3. Sanche S, Lin YT, Xu C, et al: High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerging Infectious Diseases 26 (7):1470-1477, 2020. doi:10.3201/eid2607.200282
4. Wrapp D, Wang N, Corbett KS, et al: Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367 (6483):1260-1263, 2020. doi: 10.1126/science.abb2507
5.The COVID Tracking Project at The Atlantic: State of the States: Florida. https://covidtracking.com/data/state/florida#historical Accessed July 23,2020.
6. Centers for Disease Control and Prevention: Coronavirus Disease 2019 (COVID-19): Implementation of Mitigation Strategies for communities With Local COVID-19 transmission. Atlanta, GA, US Department of Health and Human Services, Centers for Disease Control and Prevention. Updated May 27, 2020. Accessed July 23, 2020. https://www.cdc.gov/coronavirus/2019-ncov/community/community-mitigation.html
7. Centers for Disease Control and Prevention: Coronavirus Disease 2019 (COVID-19): Considerations for Events and Gatherings. Atlanta, GA, US Department of Health and Human Services, Centers for Disease Control and Prevention. Updated July 7, 2020. Accessed July 23, 2020. https://www.cdc.gov/coronavirus/2019-ncov/community/large-events/considerations-for-events-gatherings.html