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Virulence evolution in SARS-CoV2

In a recent report, healthcare workers accounted for 11% (1,689 of 15,194) of reported cases. It is clear that being a healthcare worker is a risk factor for symptomatic COVID-19 disease. It is less clear if health care workers get sicker than the general population when infected.  Severe disease in healthcare workers might occur because they are exposed to more sick patients. Others have proposed that doctors and nurses receive a higher viral inoculum (higher dose) when they are exposed. Another possibility is that hospital acquired strains are more virulent than those acquired in the community. These explanations may all be simultaneously true. This post will examine the possibility that virulence characteristics of the virus might be responsible for worse disease in front-line healthcare workers.

Early reports suggested that more than one strain – a less virulent and a more virulent strain – were circulating in China. That remains uncertain. Further work will be needed to understand whether the virus is evolving to be less or more virulent. However, we know that such a thing is possible because it has happened before.

In an article describing the original “classic” SARS, the 2003 outbreak that originated in Guangdong China, Wang and Jolly (2004) explored the evolution of virulence in a paper entitled “Changing virulence of the SARS virus: the epidemiological evidence.”

The strain that spread from Hong Kong to Singapore, Toronto and VietNam, and later to Beijing and Taipei, was more virulent, and mortality rates were higher. Evolution towards increasing virulence is favoured in circumstances in which there are reproductive advantages for the pathogen (15). Changes in the strain resulting in increased virulence may accompany increased excretion (by coughing and sneezing, for example), which enhances the evolutionary fitness of the virus by allowing it to infect and reproduce in more hosts. Also, within health-care settings, the more seriously ill a patient becomes, the more contact he or she requires with health professionals, making health professionals the vector for the infection; the virus is thus passed on to a large pool of susceptible people, in intensive care for example, who are likely to have serious pre-existing medical conditions. The deadliness of hospital-acquired group B streptococcus, as opposed to that which is acquired in the community, is an example of the ability of organisms to adapt and reproduce within health-care settings despite rigorous interventions to prevent transmission (15). The influenza pandemic of 1918 (15) during which the virus spread rapidly through people living in close proximity precluded the need for the host to travel in order for the virus to spread. This echoes the conditions in many hospitals affected by SARS-CoV and explains the success of the virus in spreading through the apartment complex in Hong Kong and the market in Singapore and its lack of success in spreading outside of those settings.”

Reference (15) is Paul Ewald’s Evolution of infectious disease. 1st ed. Oxford: Oxford University Press; 1994. p. 6, 118. Ewald and others have written extensively about the tradeoff between virulence and transmission. Read Evolution of virulence by Paul Ewald (2004).

The key take home point here is that hospitals are locations that can select for the evolution of more virulent pathogens. This happens for several reasons. First, we cluster sick and vulnerable patients close together. When sick people are closely clustered, and when there is inattention to infection control (which happens all too often in nursing homes and long term health care facilities), it provides ample opportunities for transmission, even when patients are bedridden. At the same time, health care workers can inadvertently transmit the disease between sick patients, and to each other. By analogy, healthcare workers are vectors, akin to mosquitoes that transmit malaria. Vector-borne disease tend to be more virulent than directly transmitted diseases (in general). Vector transmission and patient clustering in hospitals circumvents a main tradeoff – that between pathogen virulence and transmission – (explained in Vaughn Cooper’s video available here) – that restrains virulence in many community acquired infectious diseases.

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We wrote about this in Alcock and Schwartz A clinical perspective in Evolutionary Medicine: What we wish we had learned in medical school:

“Most physicians do not realize that their bad habits might be responsible for the evolution of virulent strains of bacteria in hospitals (Ewald 2004). Virulence describes the capacity of a parasite or pathogen to harm its host. Virulent host–pathogen relationships can evolve depending on the mode of transmission (Day 2002; Ewald 2004). Infections are often more virulent and more deadly when they are transmitted by an outside agent, such as a needle, a clinician’s hands, or a mosquito (Ewald 2004). ”

We were talking about bad habits around hand washing, but mask-wearing, and PPE use are equally applicable. Knowing how this works puts us back in control:

“…interventions that reduce the frequency of transmission opportunities will favor pathogens that cause less damage… Simple public health measures, like hand washing, will decrease the infectious inoculum, help prevent disease outbreaks, as well as promote the evolution of less virulent pathogens.”

In other words, what we do in hospitals can shape the evolution of virulence in pathogens like SARS-CoV2. Public health measures and governor’s orders to social distance and stay at home might affect the evolution of pathogen virulence, perhaps to an even greater degree. Since various US states and locales have different socially distancing orders we might be able to test this Ewaldian proposition during this epidemic.

Categories: Uncategorized

Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine

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