Text by Dr. Michael Zapor, Copyright 2020
Being an infectious diseases physician, research microbiologist, and former deputy commander of the Walter Reed Army Institute of Research (which is in the business of identifying, researching, and mitigating infectious disease threats), I thought I’d make a few comments about Coronavirus Disease-2019.
Firstly, we’ve known about coronaviruses since the 1960s. Named for the crown-like arrangement of glycoproteins on their capsid, the coronaviruses comprise a family within the order Nidovirales and consist of four genera: alpha, beta, gamma, and delta. Coronaviruses are common in birds and mammals (with the greatest diversity in bats), and human infections are caused by two alpha- (i.e. HCoV-229E and HCoV-NL63) and several beta- (e.g. HCoV-OC43 and HCoV-HKU1) species. Severe Acute Respiratory Syndrome coronavirus (SARS) and Middle East Respiratory Syndrome coronavirus (MERS) are also beta-coronaviruses. Coronaviruses are ubiquitous and along with rhinoviruses, parainfluenza, metapneumovirus, and respiratory syncytial virus, cause most community-acquired upper respiratory tract infections (i.e. the common cold). As with other respiratory viruses, coronaviruses occasionally cause more severe illness. Individuals at the extremes of age (i.e. infants and the elderly), as well as those with comorbid pulmonary disease (e.g. chronic obstructive pulmonary disease), or immune compromising conditions (e.g. hematopoietic stem cell transplant or HIV infection) are at increased risk. Certain coronavirus species (e.g. HCoV-OC43, SARS-CoV, and MERS-CoV) also are associated with more severe infection. Except for SARS-CoV and MERS-CoV, there has not been much interest in producing coronavirus vaccines. This derives from the fact that most coronaviruses: 1) cause mild, self-limiting illness; 2) are difficult to replicate in tissue culture; 3) display antigenic variation (That is to say that the surface proteins against which protective antibodies would be made change); and 4) Vaccine trials with at least one animal coronavirus demonstrated a worse outcome upon challenge with the virus (a problem similarly posed by dengue virus). Although some medicines, including antivirals and chloroquine, have demonstrated potent in vitro antiviral activity against tested coronaviruses (i.e. SARS-CoV, HCoV-229E, and HCoV-OC43), there are no clinical trials assessing efficacy and treatment is supportive. As with other respiratory viruses (such as rhinoviruses), coronaviruses are transmitted by respiratory aerosol, and the mainstay of prevention is handwashing, respiratory hygiene (i.e. covering the cough or sneeze), and disinfection of fomites (i.e. inanimate objects which can become contaminated).
The coronavirus now in the news emerged in late 2019 as a novel variant out of Wuhan, a city in the Hubei Province of China—hence, its earlier designation 2019-NCoV (i.e. 2019 Novel Coronavirus). Since it is no longer novel and is genetically and clinically like SARS, 2019-NCoV was re-designated SARS-CoV-2. SARS-CoV-2 has subsequently spread to other countries including South Korea, Italy, Iran, and Japan. Most cases have been among people who had either traveled from China or who had been exposed to someone known to be infected with SARS-CoV-2. However, several cases in the United States were recently diagnosed among people with no obvious risk factors, suggesting that community transmission is occurring. The incubation period for SARS-CoV-2 appears to average 3-6 days. Because viral DNA has been isolated from respiratory secretions of exposed asymptomatic individuals, it is believed that not everyone who is exposed will become ill. The extent to which these individuals transmit SARS-CoV-2 to others is not yet known. Epidemiological studies of the Wuhan outbreak suggest that most infected individuals will have mild disease (81%), and only a minority will develop pneumonia (14%) or pneumonia with respiratory failure, shock, or multiorgan dysfunction (5%).The overall estimated case fatality rate (CFR) appears to be ~2.3%, making it less deadly than some influenza strains and far less deadly than MERS. Moreover, the CFR was lower outside of Wuhan (0.7%) and as with other coronaviruses, risk factors for severe or critical disease include extremes of age, comorbid illness, and immune compromising conditions.
SARS-CoV-2 RNA detection is by means of polymerase chain reaction (PCR) amplification, using an assay that is currently only available (in the U.S.) at the Centers for Disease Control and CDC-qualified labs. However, there is a push to make the assay more available (e.g. to state health labs). Currently, the treatment of individuals infected with SARS-CoV-2 is supportive, but antiviral drugs including nucleotide analogues and protease inhibitors are being studied. As with other coronaviruses, the mainstay of prevention is handwashing, respiratory hygiene, and disinfection of fomites. Several labs, both in the U.S. and in Israel, are pursuing a SARS-CoV-2 vaccine, buoyed by the stability of at least some of the spike glycoproteins as well as sequence homology with several other human and poultry coronaviruses. It is also possible that as more and more people become exposed to SARS-CoV-2 and develop protective antibodies, transmission between susceptible individuals will decline (the “herd effect”).
Although the emergence of a novel pathogen is never a trifling matter, it is important for people to have a realistic understanding of the disease caused by it without succumbing to hysteria. To date, SARS-CoV-2 has shown itself to be a respiratory viral pathogen most commonly causing mild, self-limiting illness, with more severe disease limited to certain susceptible populations (in contrast, say, to the 1918 H1N1 influenza virus which disproportionately killed healthy younger people). Moreover, researchers are making progress in developing vaccines and therapeutics. I certainly don’t mean to trivialize SARS-CoV-2. However, I’ve seen far more lethal viral pathogens such as HIV, rabies, Ebola, and other viral hemorrhagic fever viruses; and unless something changes with the virus, I am only moderately alarmed by SARS-CoV-2.
On a positive note, the anti-vaxxers suddenly seem awfully quiet on social media…
About The Author: Dr. Michael Zapor is the Chief of Medical Services at Veterans Affairs Medical Center in West Virginia.
1) Dr. Zapor did not write this essay in any official capacity.
2) Because the COVID situation is developing rapidly, some things included in the essay (e.g. case fatality rates) are a bit outdated.