Protection afforded by post-infection SARS-CoV-2 vaccine doses: a cohort study in Shanghai
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Curated by eLife
eLife assessment
This valuable work by Zheng and colleagues uses a large cohort database from Shanghai to identify that post-infection vaccination among previously vaccinated individuals provides significant low to moderate protection against re-infection. The evidence supporting the conclusion is solid with some limitations, e.g., lack of symptom severity as an outcome, no inclusion of time since infection as an independent variable, improper definitions of some key variables, difficult-to-interpret figures, and exclusion of key groups (infected and then vaccinated). This study will be of interest to vaccinologists, public health officials and clinicians.
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Abstract
In many settings, a large fraction of the population has both been vaccinated against and infected by SARS-CoV-2. Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April-May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHR).275,896 individuals were diagnosed with RT-PCR-confirmed SARS-CoV-2 infection in April-May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% CI 0.79-0.85). For patients who had received one, two or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76-0.93), 0.87 (0.83-0.90) and 0.96 (0.74-1.23), respectively. Vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44-0.58), and 0.67 (0.61-0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.
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eLife assessment
This valuable work by Zheng and colleagues uses a large cohort database from Shanghai to identify that post-infection vaccination among previously vaccinated individuals provides significant low to moderate protection against re-infection. The evidence supporting the conclusion is solid with some limitations, e.g., lack of symptom severity as an outcome, no inclusion of time since infection as an independent variable, improper definitions of some key variables, difficult-to-interpret figures, and exclusion of key groups (infected and then vaccinated). This study will be of interest to vaccinologists, public health officials and clinicians.
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Reviewer #1 (Public Review):
Summary:
Zheng and colleagues assessed the real-world efficacy of SARS-CoV-2 vaccination against re-infection following the large omicron wave in Shanghai in April 2022. The study was performed among previously vaccinated individuals. The study successfully documents a small but real added protective benefit of re-vaccination, though this diminishes in previously boosted individuals. Unsurprisingly, vaccine preventative efficacy was higher if the vaccine was given in the month before the 2nd large wave in Shanghai. The re-infection rate of 24% suggests that long-term anti-COVID immunity is very difficult to achieve. The conclusions are largely supported by the analyses. These results may be useful for planning the timing of subsequent vaccine rollouts.
Strengths:
The strengths of the study are a very large …
Reviewer #1 (Public Review):
Summary:
Zheng and colleagues assessed the real-world efficacy of SARS-CoV-2 vaccination against re-infection following the large omicron wave in Shanghai in April 2022. The study was performed among previously vaccinated individuals. The study successfully documents a small but real added protective benefit of re-vaccination, though this diminishes in previously boosted individuals. Unsurprisingly, vaccine preventative efficacy was higher if the vaccine was given in the month before the 2nd large wave in Shanghai. The re-infection rate of 24% suggests that long-term anti-COVID immunity is very difficult to achieve. The conclusions are largely supported by the analyses. These results may be useful for planning the timing of subsequent vaccine rollouts.
Strengths:
The strengths of the study are a very large and unique cohort based on synchronously timed single infection among individuals with well-documented vaccine histories. Statistical analyses seem appropriate. As with any cohort study, there are potential confounders and the possibility of misclassification and the authors outline limitations nicely in the discussion.
Weaknesses:
(1) Partially and fully vaccinated are never defined and it is difficult to understand how this differs from single, and double, booster vaccines. The figures including all of these groups are a bit confusing for this reason.
(2) Figure 3 is a bit challenging to interpret because it is a bit atypical to compare each group to a different baseline (ie 2V-I-V vs 2V-I). I would label the y-axis 2V-I-V vs 2V-I (change all of the labels) to make this easier to understand.
(3) A 15% reduction in infection is quite low. It would be helpful to discuss if any quantitative or qualitative signals suggest at least a reduction in severe outcomes such as death, hospitalization, ER visits, or long COVID. I am not sure that a 15% reduction in cases supports extra vaccination without some other evidence of added benefit.
(4) Why exclude the 74962 unvaccinated from the analysis. it would be interesting to see if getting vaccinated post-infection provides benefits to this group
(5) Pudong should be defined for those who do not live in China.
(6) The discussion about healthcare utilization bias is welcomed and well done. It would be great to speculate on whether this bias might favor the null or alternative hypothesis.
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Reviewer #2 (Public Review):
Summary:
This paper evaluates the effect of COVID-19 booster vaccination on reinfection in Shanghai, China among individuals who received primary COVID-19 vaccination followed by initial infection, during an Omicron wave.
Strengths:
A large database is collated from electronic vaccination and infection records. Nearly 200,000 individuals are included in the analysis and 24% became reinfected.
Weaknesses:
The article is difficult to follow in terms of the objectives and individuals included in various analyses. There appear to be important gaps in the analysis. The electronic data are limited in their ability to draw causal conclusions.
More detailed comments:
In multiple places (abstract, introduction), the authors frame the work in terms of understanding the benefit of booster vaccination among individuals …
Reviewer #2 (Public Review):
Summary:
This paper evaluates the effect of COVID-19 booster vaccination on reinfection in Shanghai, China among individuals who received primary COVID-19 vaccination followed by initial infection, during an Omicron wave.
Strengths:
A large database is collated from electronic vaccination and infection records. Nearly 200,000 individuals are included in the analysis and 24% became reinfected.
Weaknesses:
The article is difficult to follow in terms of the objectives and individuals included in various analyses. There appear to be important gaps in the analysis. The electronic data are limited in their ability to draw causal conclusions.
More detailed comments:
In multiple places (abstract, introduction), the authors frame the work in terms of understanding the benefit of booster vaccination among individuals with hybrid immunity (vaccination + infection). However, their analysis population does not completely align with this framing. As best as I can tell, only individuals who first received COVID-19 vaccination, and subsequently experienced infection, were included. Why the analysis does not also consider individuals who were infected and then vaccinated is not clear.
In vaccine effectiveness analyses, why was time since initial infection not examined as a modifier of the booster effect? Time since the onset of the Omicron wave is only loosely tied to the immune status of the individual.
The effect of booster vaccination on preventing symptomatic vs. asymptomatic reinfection does not appear to have been evaluated; this is a key gap in the analysis and it would seem the data would support it.
In lines 105-108, the demographic description of the analysis population is incomplete. Is sex or gender identity being described? Are any individuals non-binary? What is the age distribution? (Only the proportions 20-39 and under 6 are stated.)
Figure 1 consort diagram is confusing. In the last row, are the two boxes independent or overlapping sets of individuals? Are all included in secondary analyses?
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