Transmissibility, Viability, and Fatality of SARS-CoV-2
By Michael Zapor, MD, PhD, CTropMed, FACP, FIDSA (14 April 2020)
(Shared with permission)
In my four prior coronavirus disease (COVID-19)-related posts, I gave a general overview of coronaviruses, including SARS-CoV-2, the virus that causes COVID-19 (1 and 13 March 2020), a review of investigational therapeutics and vaccines currently being studied (23 March and 6 April), and a discussion about the role of masks in providing protection from COVID-19 (6 April 2020). In this post, I discuss three noteworthy aspects of SARS-CoV-2 about which I am frequently asked. These include:
2) viability on inanimate surfaces, and
3) the associated case fatality rate.
Transmissibility refers to the ease with which a pathogen is transmitted from one person to another. Human-to-human transmission of SARS-CoV-2 was first documented in a family that traveled together to Wuhan city, Hubei province, China in December 2019. Of six family members, five were quickly infected (giving an attack rate of 83%), suggesting that the virus is highly transmissible. Subsequent epidemiological studies indicated that the reproductive number (R0) of SARS-CoV-2 is ~2.68 (The reproductive number refers to the number of expected cases caused by one infected individual in a susceptible population).
Simply put, one person with COVID-19 will likely infect 2–3 other individuals before that individual is no longer contagious. By way of comparison, the R0 of other notable coronaviruses ranges from 0.3–0.8 (MERS-CoV) to 2–5 (SARS-CoV-1), and that of the 1918 pandemic influenza strain was 1.4–2.8. With an R0 of 2.68, SARS-CoV-2 is roughly comparable to coronaviruses that cause the common cold. As an aside, measles, which has an R0 of 12–18, is considered to be the most contagious clinically relevant virus of man.
Although SARS-CoV-2 is transmitted through the air, it isn’t clear whether transmission is exclusively via droplets (e.g. by cough), or whether airborne transmission (i.e. by exhalation) also occurs. This distinction is relevant because airborne pathogens are generally more transmissible than those spread by droplets. In addition to being carried in an exhaled breath, they tend to travel farther and remain suspended in the air longer than do droplet-borne pathogens. Whether SARS-CoV-2 is spread by droplets or aerosol is also relevant because airborne precautions require additional personal protective equipment (PPE) such as a Powered Air-Purifying Respirator (PAPR), which tends to be in more limited supply. Examples of pathogens known to be spread by airborne transmission include Measles, Severe Acute Respiratory Syndrome coronavirus (i.e. SARS-CoV-1), Varicella (chickenpox), and Mycobacterium tuberculosis (Ital.). In a recent concise communication, researchers reported that SARS-CoV-2 aerosolized by means of a three-jet Collison nebulizer remained suspended for three hours. However, this was an artificial scenario not necessarily reflective of a cough; and presently, both the CDC and the WHO state that transmission of SARS-CoV-2 is primarily via droplets, and that the role of aerosols is uncertain. For many hospitals, N95 respirators and face shields are recommended for healthcare workers tending to COVID patients, while PAPR are recommended for those engaged in aerosol-generating procedures such as intubation and suctioning. (For a brief discussion of the N95 respirator, see my post, dated 6 April 2020.)
Before changing topics, I’ll briefly comment on the role of infected asymptomatic individuals in transmitting SARS-CoV-2. There are a number of pathogens that can be transmitted before the onset of symptoms (i.e. during the incubation period), including the influenza and herpes simplex viruses; and several studies have documented that SARS-CoV-2 is also shed in respiratory secretions up to 1–2 days before and up to 30 days after symptoms. However, because these studies employed polymerase chain reaction (PCR) amplification, which detects nucleic acid and cannot distinguish viable from nonviable virus, the significance of shedding by asymptomatic persons is not yet known. Nonetheless, I suspect that additional studies, involving viral culture rather than PCR, will show that asymptomatic individuals do indeed infect others; and viral shedding by asymptomatic persons is the basis for the recent CDC recommendation that everyone should consider wearing a face covering in community settings.
Any discussion of a pathogen’s transmissibility should include the role, if any, of fomites. A fomite is an inanimate object that, when contaminated with an infectious agent, can serve in the transfer of that agent between people. Examples of fomites include doorknobs, water fountains, and discarded tissues. Unlike some other microorganisms (such as fungi and sporulating bacteria), viruses cannot survive for long outside of a susceptible host. However, there is considerable variability in how long a particular virus remains viable on an inanimate surface (Note: I intentionally use the word “viable” rather than “alive” because the latter has existential implications). Human Immunodeficiency Virus (HIV) for example, is quickly inactivated on inanimate surfaces, and fomites do not generally play a role in HIV transmission (excluding things like blood-containing syringes and needles). In contrast, enteric viruses like hepatitis A virus remain viable for weeks on surfaces and fomites do play a role in their transmission. As for SARS-CoV-2, recent studies suggest that the virus remains viable for up to four hours on copper, up to 24 hours on cardboard, and up to two to three days on plastic and stainless steel.
The third and final topic I want to address in this post is the SARS-CoV-2 case fatality rate (CFR), which is defined as the proportion of people who die from SARS-CoV-2 among all individuals diagnosed with the disease over a certain period of time. In mathematical terms, CFR is depicted as a fraction, in which the denominator is the number of people diagnosed and the numerator is the number of people who die; the numerator is divided by the denominator, with the resulting decimal then multiplied by 100 to yield a percentage. Some examples of infectious diseases with a CFR ~100% (i.e. almost invariably fatal) include rabies, primary amoebic meningoencephalitis, visceral leishmaniasis, African trypanosomiasis, and the transmissible spongioform encephalopathies. In contrast, varicella (chickenpox) and hepatitis A are two examples of infectious diseases associated with a low (< 1%) CFR. As of the time I am writing this post, the WHO reports 1,812,734 confirmed COVID-19 cases globally with 113,675 deaths. This translates to a CFR of 6.3 %, meaning that for every one hundred people diagnosed with COVID-19, about six die. (Note that other sources calculate the current CFR to be closer to 5 percent.) By comparison, the estimated CFR for the 1918 influenza (“Spanish flu”) pandemic, with which the current pandemic has been compared, was > 2.5%.
However, there is considerable variation in the COVID-19 CFR reported by each country, with Italy reporting one of the highest CFR (9.26%), and Germany one of the lowest (0.13%). There are likely several reasons for this discordance. First of all, with 23% of Italians aged 65 years or older, Italy has the oldest population in Europe. When stratified for age, Italy’s CFR is very similar for people younger than 69 years but remains disproportionately higher for the elderly.
One possible explanation for this may be the fact that there is no clearly defined definition of death by COVID-19. In Italy, for example, death by COVID-19 is simply defined as a death in someone who was diagnosed with COVID-19 — that is to say, without consideration of pre-existing conditions and co-morbid illness. Consequently, an elderly man with coronary artery disease who is diagnosed with COVID-19 and subsequently suffers a fatal myocardial infarction has COVID-19 listed as the cause of death. When a more rigorous definition that accounts for co-morbid disease is applied, Italy’s COVID-19 CFR is significantly lower.
Other factors that likely contribute to variations in reported CFR include the availability of health care and the extent of testing. The former can be illustrated by the example in which fifteen critically ill COVID-19 patients are admitted to a hospital with a ten-bed intensive care unit. Perhaps all fifteen patients would survive with appropriate intensive care but are unlikely to survive otherwise. Unless five patients can be transferred to another ICU, a difficult choice needs to be made. Indeed, many hospitals, including mine, have anticipatorily stood up Scarce Resource Allocation Committees to determine the allotment of critical care beds and ventilators, weighing such considerations as the Sequential Organ Failure Assessment (SOFA) Score, which is a mortality prediction metric.
Lastly, the CFR is also impacted by the extent of testing for the disease. Recall that in our mathematical calculation of CFR, the denominator is the number of individuals diagnosed. If mildly symptomatic individuals are tested, more individuals will be diagnosed, the denominator will increase, and the overall number will decrease. This likely explains, at least in part, the lower CFR reported by countries like South Korea, where there is more extensive testing. In the United States, where testing is increasingly available, the reported CFR is currently somewhere between 1.4 and 3.1 percent.
In this post, I focused on three aspects of SARS-CoV-2: the virus’ transmissibility, the role of fomites, and the associated case fatality rate. Although SARS-CoV-2 is neither as transmissible (e.g. measles), as lethal (e.g. rabies), nor as persistent on fomites (e.g. hepatitis A) as are some other viruses, the combination of its ease of transmission, persistence on inanimate surfaces, and a respectable case fatality rate make it noteworthy; and in these respects, the current pandemic resembles that of the 1918 influenza pandemic.
However, this is caveated by several important differences between the two, including the fact that the 1918 “Spanish flu” was associated with a disproportionately higher mortality rate in healthy young people — something that is not a feature of SARS-CoV-2. Although the reason for this is unknown, one hypothesis is that a similar H1N1 strain had circulated previously, and that older individuals, who might have been children then, had partial immunity when the 1918 strain emerged many years later. Nonetheless, the similarities and dissimilarities between the current pandemic and that of 1918, while interesting, are beyond the intended scope of this post.
As with my previous posts, my intention here is neither to sensationalize nor trivialize, but simply to provide information and, whenever possible, to alleviate anxiety.
Until my next update — regards.
Michael Zapor, MD, PhD, CTropMed, FACP, FIDSA
(14 April 2020)