MMWR: Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination

[Michael Coston]

MMWR: Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination

Credit ACIP/CDC

#16,108

Among the arguments frequently seen on social media against getting the COVID vaccine - one of the most common insists that if you've already had a COVID infection - you are better protected than if you'd taken the vaccine.

While plausible, as with so many of these blanket declarations, evidence is never provided. This argument is predicated, I suppose, on the common belief that `natural is always better than artificial'. ​

Recent history suggests that may not be so - with the constant introduction of new variants - we've seen huge numbers of reinfections in places like Brazil (see The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence), and research on other coronaviruses (see Nature Medicine: Seasonal Coronavirus Protective Immunity Is Short-Lasting), have demonstrated that natural immunity can be short lived.

In fairness, we've also seen breakthrough infections among the vaccinated, so neither provides complete protection. But the assumption that once you are infected and recovered you are immune to reinfection, is specious.​

Reinfection data on the Delta variant - which has risen to dominance over the past couple of months - is just coming in, but today we have a early release from the CDC's MMWR that finds that among those who have been previously infected with COVID, those that are also vaccinated have a far lower risk of reinfection.

This study took place mostly during at a time (May-June 2021) when the Alpha variant peaked in the United States, and before Delta took full control (see CDC chart below). ​

I've only include the link, summary, and some extended excerpts from the report. Follow the link to read it in its entirety.

Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination — Kentucky, May–June 2021
Early Release / August 6, 2021 / 70​

​

Alyson M. Cavanaugh, DPT, PhD1,2; Kevin B. Spicer, MD, PhD2,3; Douglas Thoroughman, PhD2,4; Connor Glick, MS2; Kathleen Winter, PhD2,5 (View author affiliations)View suggested citation​

Summary

What is already known about this topic?

Reinfection with human coronaviruses, including SARS-CoV-2, the virus that causes COVID-19, has been documented. Currently, limited evidence concerning the protection afforded by vaccination against reinfection with SARS-CoV-2 is available.

What is added by this report?

Among Kentucky residents infected with SARS-CoV-2 in 2020, vaccination status of those reinfected during May–June 2021 was compared with that of residents who were not reinfected. In this case-control study, being unvaccinated was associated with 2.34 times the odds of reinfection compared with being fully vaccinated.

What are the implications for public health practice?

To reduce their likelihood for future infection, all eligible persons should be offered COVID-19 vaccine, even those with previous SARS-CoV-2 infection.​

Table 1
Table 2
References​

Related Materials

PDF pdf icon[422K]​

Although laboratory evidence suggests that antibody responses following COVID-19 vaccination provide better neutralization of some circulating variants than does natural infection (1,2), few real-world epidemiologic studies exist to support the benefit of vaccination for previously infected persons.

This report details the findings of a case-control evaluation of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May–June 2021 among persons previously infected with SARS-CoV-2 in 2020.​

Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58–3.47).​

These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection. To reduce their risk of infection, all eligible persons should be offered vaccination, even if they have been previously infected with SARS-CoV-2.*​

(SNIP)​

Discussion

This study found that among Kentucky residents who were previously infected with SARS-CoV-2 in 2020, those who were unvaccinated against COVID-19 had significantly higher likelihood of reinfection during May and June 2021. This finding supports the CDC recommendation that all eligible persons be offered COVID-19 vaccination, regardless of previous SARS-CoV-2 infection status.

Reinfection with SARS-CoV-2 has been documented, but the scientific understanding of natural infection-derived immunity is still emerging (5). The duration of immunity resulting from natural infection, although not well understood, is suspected to persist for ≥90 days in most persons.** The emergence of new variants might affect the duration of infection-acquired immunity, and laboratory studies have shown that sera from previously infected persons might offer weak or inconsistent responses against several variants of concern (2,6).​

​

For example, a recent laboratory study found that sera collected from previously infected persons before they were vaccinated provided a relatively weaker, and in some cases absent, neutralization response to the B.1.351 (Beta) variant when compared with the original Wuhan-Hu-1 strain (1). Sera from the same persons after vaccination showed a heightened neutralization response to the Beta variant, suggesting that vaccination enhances the immune response even to a variant to which the infected person had not been previously exposed.

Although such laboratory evidence continues to suggest that vaccination provides improved neutralization of SARS-CoV-2 variants, limited evidence in real-world settings to date corroborates the findings that vaccination can provide improved protection for previously infected persons. The findings from this study suggest that among previously infected persons, full vaccination is associated with reduced likelihood of reinfection, and, conversely, being unvaccinated is associated with higher likelihood of being reinfected.​

The lack of a significant association with partial versus full vaccination should be interpreted with caution given the small numbers of partially vaccinated persons included in the analysis (6.9% of case-patients and 7.9% of controls), which limited statistical power. The lower odds of reinfection among the partially vaccinated group compared with the unvaccinated group is suggestive of a protective effect and consistent with findings from previous studies indicating higher titers after the first mRNA vaccine dose in persons who were previously infected (7,8).

(SNIP - Limitations)

These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection. Among previously infected Kentucky residents, those who were not vaccinated were more than twice as likely to be reinfected compared with those with full vaccination. All eligible persons should be offered vaccination, including those with previous SARS-CoV-2 infection, to reduce their risk for future infection.​

(Continue . . . )


The CDC issued a press release on these findings (embargoed until 1pm EST today), which urges everyone to get vaccinated regardless of previous infection history.

New CDC Study: Vaccination Offers Higher Protection than Previous COVID-19 Infection​

While I doubt there is any amount of scientific data that will convince hardcore vaccine skeptics, hopefully - for those merely on the fence about getting vaccinated - this study might provide some additional impetus.

While this certainly won't be the last word on the subject - and new variants could change the equation - those of us who are both fully vaccinated and previously had a bout with the virus can probably take some degree of comfort in the fact that we may be more protected as a result.​

And more than 18 months into this pandemic, I'll take whatever comfort I can find.

https://afludiary.blogspot.com/2021/08/mmwr-reduced-risk-of-reinfection-with.html

 

[Emily]

The findings in this report are subject to at least five limitations. First, reinfection was not confirmed through whole genome sequencing, which would be necessary to definitively prove that the reinfection was caused from a distinct virus relative to the first infection. Although in some cases the repeat positive test could be indicative of prolonged viral shedding or failure to clear the initial viral infection (9), given the time between initial and subsequent positive molecular tests among participants in this study, reinfection is the most likely explanation. Second, persons who have been vaccinated are possibly less likely to get tested. Therefore, the association of reinfection and lack of vaccination might be overestimated. Third, vaccine doses administered at federal or out-of-state sites are not typically entered in KYIR, so vaccination data are possibly missing for some persons in these analyses. In addition, inconsistencies in name and date of birth between KYIR and NEDSS might limit ability to match the two databases. Because case investigations include questions regarding vaccination, and KYIR might be updated during the case investigation process, vaccination data might be more likely to be missing for controls. Thus, the OR might be even more favorable for vaccination. Fourth, although case-patients and controls were matched based on age, sex, and date of initial infection, other unknown confounders might be present. Finally, this is a retrospective study design using data from a single state during a 2-month period; therefore, these findings cannot be used to infer causation. Additional prospective studies with larger populations are warranted to support these findings.

And no antibody testing was done in the supposedly infected group to confirm they were really infected and not just false positive PCR tests.
Really what should be compared is naturally infected boosted by another natural infection vs natural infection plus boosting by later vaccination.

I don't see a good motive for mass vaccinating or boosting natural immunity of the young & healthy, (and that includes not overweight). But that will eliminate the control group if things go bad with the vaccines and we see ADE.

https://www.biorxiv.org/content/10.1101/2021.07.29.454333v1
"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern"

"We conclude that memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination."

 

[JJackson]

Natural infection will create a broad B and T cell response but not targeted at those peptides most likely to provide sterilising immunity, in addition the strength of the immune response is correlated to the severity of infection. The RNA and Ad vaccines produce a more consistent response but only to the Spike (which is a small part of the whole genome) but produces the most potent antibodies and concentrates the immune response to the most useful antibodies and memory cells. There is now enough data to show fairly conclusively that on average you are better protected by vaccination than prior infection and that infection followed by vaccination gives you the best of both worlds, some protection across all the viral proteins plus a boosted repertoire covering the RBD and N terminal domain which constitute the sterilising immune epitopes.
ADE was a legitimate concern at the start of the vaccination campaign but if it was going to be a problem that would have become apparent soon after the start of mass vaccination.

 

[Emily]

JJackson, there is no proof at this point that vaccination is superior to immunity from natural infection. The currently apparent value of vaccination is in preventing hospitalization in susceptible people. People with natural immunity seem just as protected in countries with solid data. Israel and other countries recognize this but the US does not. The US has a powerful vaccine industry that seems determined to vaccinate everyone with natural immunity. It's peculiar.

ADE is far from ruled out:

https://www.sciencedirect.com/science/article/pii/S2211124721000127
"Antibodies from our donor bound to five non-overlapping RBD
epitopes, similar to other studies reporting three or four distinct
antigenic sites within RBD (Liu et al., 2020a; Robbiani et al.,
2020; Rogers et al., 2020; Wec et al., 2020; Wu et al., 2020c;
Zost et al., 2020a). Importantly, we found a significant association
of ADE with one of five non-overlapping antibody binding
RBD epitopes. This was a surprising result given that no such
epitope-ADE relationship has ever been reported for coronaviruses
to the best of our knowledge. The underlying mechanism
warrants further investigation."

 

[JJackson]

Emily have a look at
Protection afforded by the BNT162b2 and mRNA-1273 COVID-19 vaccines in fully vaccinated cohorts with and without prior infection
https://www.medrxiv.org/content/10.1101/2021.07.25.21261093v1
and
Neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination: a systematic review and pooled meta-analysis https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciab646/39306079/ciab646.pdf

An in vitro mechanism for some class IV anti-bodies making one type of B cell susceptible, without showing that it is permissive, is interesting but is not showing any detectable real world effect. If this was a problem with any measurable clinical impact we would have seen it by now.
This will help anyone who is unfamiliar with the specific meaning of susceptible and permissive in this context. https://www.youtube.com/watch?v=pojvzGC0lWE

 

[Emily]

Thank you, JJackson. Those studies are interesting and the video helpful. You might be interested in this one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550103/
There are some rare cases like that of what looks like well-documented re-infections being worse than the first one.