2/26/2020 Matthew E Levison, MD, Adjunct Professor of Medicine, Drexel University College of Medicine
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.) The infection is believed to have originated in bats and to have made the jump to human beings at a seafood and live animal market in the city, via an intermediate host (thought to be the pangolin, a scaled, ant-eating mammal) that was being sold as exotic food at the market; 55% of the early cases were linked to that market, which was closed on Jan 1, 2020. Subsequent cases likely acquired the infection from other human cases (1). The incubation period for 95% of cases was reported to be ≤14 days, supporting a 14-day quarantine period.
After 9 weeks of sustained transmission, Hubei Province currently reports 64,084 confirmed cases with 2,346 deaths. The actual number of cases is probably much higher as only the most severe cases are likely included in reports due to shortages of testing kits. The presence of many undiagnosed mild infections is probably limiting efforts to control further spread of this infection. The rapidity of spread is high when compared to the 2003 SARS outbreak, suggesting SARS-CoV2 is much more transmissible than SARS-CoV.
Chinese authorities responded on Jan 23, 2020 by quarantining millions of people in Hubei Province. The restrictions came on the eve of Lunar New Year, when many people travel home. In fact, it was estimated that five million people left Wuhan before the lockdown began and the number of cases correspondingly surged in the surrounding Chinese provinces. Also, cases with a history of travel to or from Wuhan then began to appear outside China, in places such as Hong Kong and Singapore.
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
• Touching virus-contaminated surfaces and then touching the eyes, nose or mouth
• Possibly inhaling small airborne respiratory emissions containing the virus
• 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.
Could it be a Pandemic?
A pandemic involves sustained transmission through multiple generations of the infectious agent in many countries on a global scale. Up until now, almost 98% of cases have occurred in China. COVID-19 outside China has involved mainly travelers who became infected in China. Sustained transmission of SARS-CoV2 outside China has occurred in only a few countries, but the pattern is clearly changing rapidly. Just over a recent 48-hour period, from Feb 21 to Feb 23, the number of cases reported from S. Korea more than doubled from 204 to 602; South Korea is now second only to China in number of cases. The number of cases also increased dramatically over a few days in Iran recently from 0 to 43, and in Italy from 3 to 132. We have no data on the presence of COVID-19 in resource-poor regions without the ability to diagnose this disease; of particular concern are countries in Africa where China has developed a large presence in the past several years (2).
A week ago, the indications of a COVID-19 epidemic occurring in the United States appeared to be low. But this is also changing rapidly. Over 48 hours, from Feb 21 to Feb 23, COVID-19 cases in the U.S. increased from 15 to 35, including 13 travel-associated cases, 18 cases among repatriated U.S. citizens from the Diamond Princess cruise ship quarantined in Japan and three cases in U.S. citizen evacuees from Wuhan. A resident of California, who had not traveled to countries in which the SARS-CoV2 virus is circulating and was not exposed to anyone known to be infected with the coronavirus, might be the first case in the United States of “community spread,” the US Centers for Disease Control and Prevention said on Wednesday, Feb 26, 2020. It now brings the number of cases in this country to 60, including the 3 cases among Americans who were repatriated from Wuhan and 42 from the Diamond Princess cruise ship, plus 15 cases confirmed in this country (3).
There is as yet no vaccine that could prevent further spread of SARS-CoV2, and no specific antiviral drugs for it. But researchers worldwide are moving quickly to test drugs such as Kaletra, a combination of two protease inhibitors, lopinavir and ritonavir, used to treat HIV/AIDS, chloroquine, an antimalarial, and remdesivir, a nucleotide analog that was originally tested against Ebola. Many organizations, including the NIH, the Chinese Center for Disease Control and Prevention, the University of Hong Kong, the University of Queensland, the University of Saskatchewan, and several pharmaceutical companies are using published genomes to develop possible vaccines against SARS-CoV-2. It is hoped that rapid vaccine and drug development can mitigate the evolution of COVID-19 into a pandemic.
Thus, the most important preventive measure is avoidance of exposure to SARS-CoV2 by means of
• Respiratory and contact precautions
Respiratory precautions involve using facemasks. Two types of facemasks are available, surgical 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 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 should wear N-95 masks, which fit very tightly, and protect the wearer from airborne respiratory emissions. Supplies of N95 facemasks and other protective equipment, such as gloves, eye shields, and gowns, can become depleted during an extended outbreak, and their use should be prioritized to those at greatest risk of exposure to contagious individuals, such as those caring for infected individuals.
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.
1. Li Q, Guan X, Wu P, et al: Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 29 Jan. 2020. doi: 10.1056/NEJMoa2001316
2. Knowledge@Wharton: China’s investment in Africa: What’s the real story? Philadelphia, Wharton School, University of Pennsylvania 16 Jan. 2016.
3. Centers for Disease Control and Prevention: Coronavirus Disease 2019 (COVID-19): COVID-19 Situation Summary. Atlanta,GA, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Updated February 26, 2020. Accessed February 27, 2020.