By Dr. Liji Thomas, MD,Oct 28 2020
A recent study published on the preprint server medRxiv* in October 2020 suggests that arguments in favor of herd immunity are weakened by the fact that the steep increase in the number of COVID-19 deaths as a result of being exposed to the virus many times instead of once or a few times is not taken.
While most have mild COVID-19, a severe disease associated with diffuse pneumonia may require hospitalization. Many in this group will eventually require intensive care, with oxygen supplementation and mechanical ventilation.
In a sizable minority of cases, death supervenes due to multi-organ failure. The survivors in this group may experience permanent disabling symptoms.
Lockdown strategies were meant to buy time for productive and preparatory measures by slowing the pace of viral transmission. Vaccines are meant to elicit neutralizing immunity to the virus and prevent endemicity. Since this is an RNA virus, it is bound to undergo numerous mutations, which will make it more difficult to eradicate it in endemic form.
Another school of thought holds that herd immunity is the best way to handle the pandemic. Without any interventions, the population will develop immunity naturally, while the economy will remain stable, so goes the argument. However, the World Health Organization (WHO) chief has termed this an unethical idea.
Issues with Herd Immunity
The researchers in the current study say that herd immunity appears appealing only because it is backed by simplistic simulations that ignore real-time health care challenges. Moreover, durable immunity to SARS-CoV-2 has not yet been proved.
Again, this model does not consider the higher death rates bound to occur with an overburdened healthcare system as infections surge. And finally, it ignores the long-term disabling effects of this illness, the medical and the social costs of caring for such individuals.
The uncontrolled viral spread will cause endemic COVID-19. Novel variants may emerge that are more destructive to lung tissue. Even worse, multiple exposures may lead to a higher viral load, and therefore a more significant proportion of severe disease.
Repeated exposures could also trigger antibody-dependent enhancement (ADE) of disease severity. This is one area where wearing face masks in public all the time could make a big difference in the load placed on hospitals and HCWs, by preventing severe infections.
There are many distinct variants of the virus in circulation at the current time. These variants do show different degrees of infectivity and pathogenicity. It is unclear whether these can exist simultaneously in one patient and how they interact, if so.
Underestimating Mortality from Early Data
Since current estimates of mortality depend on information from the early part of the pandemic, they are likely to be inaccurate since, at this time, individuals were unlikely to have repeated contacts with infected persons. One exception was HCWs, since their daily and repeated contacts with many potentially infected people rendered them capable of super-infections.
Understanding Multi Infections
The present study aims to understand how mortality is related to the presence of multiple variants of SARS-CoV-2 acquired through multiple exposures. This model also examines how measures intended to reduce contact with infected people affect super-infections and mortality. It uses a model adapted from the free tool CovidSIM.
The researchers assumed disease stages of latent (3.7 days), prodromal (1 day), fully contagious (7 days), and late infectious (7 days), and also assumed a doubling of infectivity in the fully contagious stage compared to the first two. They found that multiple infections had a ~64% risk of causing severe symptoms and 4% mortality compared to 58% and 3%, respectively, for single infections.
Morbidity from Multi Infections
Multiple infections caused more symptomatic infections, therefore more isolation, resulting in less spread and a smaller peak. But while the total number of multiple infections is somewhat reduced, especially during the epidemic’s peak, the number of deaths increases.
However, seasonal infections affect this relationship, with a higher narrower peak resulting if it overlaps with the beginning of the flu season. In this case, more multi infections, and significantly more deaths, will occur than expected.
Symptom Severity
Symptom severity is measured by the number of infected individuals who come to medical attention and enter isolation, with a direct relationship between the two parameters. Higher isolation of symptomatic multi infections reduces total infection numbers somewhat, reducing the epidemic’s peak and of multi infections.
The total mortality rises, however, due to the increased number of deaths caused by multi infections.
Increased mortality
Again, multi infections reduce the overall case number but push up the number of deaths in proportion to the case fatality rate of multi infections. Again, this is aggravated by seasonality, with a higher epidemic peak, more multi infections, and more deaths if the peak comes at the beginning of the flu season.
Risk of Multi Infection Spread
Multi infections may be caught by one or consecutive exposures. If the latter, the effects will be delayed, and in this period, the spread is limited, while recovery may occur rather than death. Thus, this subset of infected individuals does not significantly increase the total number of multi infections.
However, the higher the risk of multi infection spread, the higher is the epidemic peak, and the greater the case fatality.
Susceptibility to successive infections
Prior infection with one strain of SARS-CoV-2 may confer partial immunity to multi infections, depending on the contagious person’s stage of infection. Susceptibility is significantly less, and therefore the risk of multi infections if the susceptible person is in the late infectious phase.
While variations in susceptibility do not affect the epidemic peak, they do affect the multi infection case number. Around the peak, multi infection by exposure to two or more single infections is more likely than that due to exposure to one multi infection.
Reducing Contacts and A Second Lockdown
The researchers also found that reducing inter-individual contacts over a range of scenarios ranging from a second lockdown to no intervention would result in a delayed but not smaller epidemic peak in a non-seasonal scenario. Case isolation reduces the peak. In both cases, multi infections and deaths are unaffected.
With seasonal changes, fewer contacts can delay the epidemic peak to coincide with that of the flu season, increasing the peak height. The narrow, sharp peak limits the multi infection case number slightly, and the number of deaths is also somewhat lower.
A second lockdown, properly timed, can reduce the number of infections occurring after the relaxation of the first, if the epidemic peaks while the reproduction number is declining. The earlier such a lockdown is put into force, the more it overlaps the pandemic’s early peak, and the greater is the delay in the eventual peak. This will also result in a broader but flatter peak.
The number of cases and deaths can be still further reduced by extending an early lockdown. If too late, however, the lockdown will be ineffective as cases are already declining.
Implications
The researchers point out, “Multiple infectious contacts and longer (average) exposure to the virus is initially restricted to certain risk groups, but will become common during the pandemic peak.”
Different variants of SARS-CoV-2 may be acquired at different points by exposure to different infectious individuals. Viral diversity will also only increase during a pandemic.
Herd immunity becomes a less attractive concept given the higher viral load and multi infection risk as the pandemic progresses, coupled with more significant morbidity and mortality. Herd immunity becomes a less attractive concept versus a properly timed second lockdown. The results may vary with the duration of immunity and human behavior. For instance, some individuals may choose to avoid most forms of contact with others. The model parameters can be tweaked for several such differences.
The researchers also point out, “Notably, multi infections are not the only danger when aiming for herd immunity. An uncontrolled (or hardly controlled) pandemic inevitably renders the virus endemic.”
If so, not only will it become difficult to get rid of the virus, but it could find reservoir hosts in pet animals, escaping control measures. As viral diversity increases, so might its virulence, requiring the vaccines to be adapted each year. Multiple vaccination rounds will then be required to eradicate the virus, resulting in ADE in some individuals.
The study concludes, “Increased morbidity and mortality due to multi infections is an important but overseen risk, particularly in the context of herd immunity. Evidence-based research on multi infections is necessary.”
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