Many people are asking if we will be able to eradicate SARS-CoV-2 through herd immunity. The answer is complicated. Here are a few reasons why.
The rise of variant strains
I have already written about the immunology of SARS-CoV-2 infection and the possibility that survivors may be reinfected. A related issue concerns the rise of variant strains. Although virologists are still studying how variants arose, it appears that the approved vaccines that are currently in distribution do recognize the known novel variants. This is good. But, it is also known that the strength of the immune response engendered by prior infection with an original strain is not as strong against some of the variants, especially the ones known as P.1 and 501Y.V2.
We should exercise caution in extrapolating too far from these findings, however. Such conclusions are based on a limited number of strains and laboratory conditions. The situation in the real world may be different. A somewhat weaker immune response may still be strong enough. Or it may not.
In particular, the resurgence of Covid-19 in Manaus, Brazil seems to show that a variant can escape from the immune response generated by natural infection with prior strains. Manaus is telling because an extremely high attack rate was experienced during the first wave of the epidemic, such that the city was believed to have reached herd immunity by October 2020. Nevertheless, a major resurgence in December resulted in a second wave that exceeded the size of the first wave.
Multiple variants of the virus were detected in Manaus. One of them, referred to as P.1, is six-fold less sensitive than the original strain to an immune response generated by the original strain. Responsiveness to a vaccine-induced immune response is similarly reduced. An important open question is whether Manaus’s second wave is due to immune escape or waning immunity. This is a question that must be answered, because it has significant implications for vaccine policy, specifically the frequency and composition of any future vaccines.
Reinfection
Knowing that immunity is not perfect gives rise to a second set of questions. How effective is naturally acquired immunity? How long does it last?
A recent study is particularly informative, although it is based on a small sample size. Importantly, the study used the gold standard of genome sequencing to document that both episodes of disease did indeed reflect different infections. The particular circumstances of the patients enrolled in the study lead to three important conclusions:
- Reinfection does happen.
- Reinfection can happen even in the presence of a robust immune response.
- Reinfection can occur as early as 19 days after the first natural infection.
It still remains to ask — how often does reinfection occur? We can’t say for sure, but perhaps not too often.
There are numerous reports of people testing positive, then testing negative, and then testing positive again or going through multiple bouts of illness. But distinguishing actual reinfection from reactivation of a persistent quiescent infection is really difficult. To be sure that the two occasions reflect separate infection events requires isolating the virus from each episode and sequencing the genome of each.
A global reinfection tracker lists only 64 such cases, although the true number is almost certainly many, many times higher. The issue is simply that genetic sequencing of the virus — an approach referred to as genomic epidemiology — is not sufficiently widely practiced. With the rise of new genetic variants, the Biden administration is now trying to change that. That’s good. We need better information about the virus’s changing genetics.
Related, a preprint published in January reported on a study of infection among 18-20 year old military recruits entering basic training. The study estimated that having previously been infected with SARS-CoV-2 reduced one’s risk of subsequent infection by approximately 80%. This may be the first solid population-level measurement of the effectiveness of naturally acquired immune protection. Eighty percent is pretty good. With 29 million known cases in the US and as many as 100 million unknown cases, this means that population immunity is mounting. On the other hand, 80% is far from perfect.
Perhaps the most concerning issue is that it puts the herd immunity threshold further out of reach. An infection that generates protective response in only 80% of cases will require 25% more people to be immunized — whether through natural infection or vaccine — for the herd immunity threshold to be achieved. This level of incomplete protection, combined with the fact that more than thirty percent of Americans say they won’t take the vaccine, suggests that it may not be possible to achieve herd immunity in the US.