Impact of previous exposure to SARS-CoV-2 and of S-Trimer (SCB-2019) COVID-19 vaccination on the risk of reinfection: a randomised, double-blinded, placebo-controlled, phase 2 and 3 trial

Smolenov, Igor; Han, Htay Htay; Li, Ping; Baccarini, Carmen; Verhoeven, Carole; Rockhold, Frank; Clemens, Sue Ann Costa; Ambrosino, Donna M.; Richmond, Peter; Siber, George R.; Liang, Joshua G.; Clemens, Ralf

doi:10.1016/s1473-3099(22)00144-x

Cited by 17 publications

(31 citation statements)

References 26 publications

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“…In our study, responses to either one or two doses of BNT162b2 in seropositive individuals were greater than those seen in naïve vaccinees and a second dose in a naturally infected individual was not associated with the expected increase in IgG. It is also now well recognized that vaccination following natural exposure is associated with great vaccine effectiveness 13 , 14 , 15 compared to either natural or vaccine induced immunity alone. As suggested by our study the greater effectiveness of hybrid immunity is likely linked to enhanced immunogenicity of vaccine on the background of natural immunity and the reported increase in the breadth of immunity.…”

Section: Discussioncontrasting

confidence: 42%

“…However such immunity, induced after natural infection, is becoming of critical interest due to the observation that vaccination following infection may provide more robust immunity than either infection or vaccination alone. 13 , 14 , 15 , 16 This so called hybrid immunity 17 is associated with a breadth of variant recognition that appears to be a consequence of immune maturation. 18 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

Zar¹,

MacGinty²,

Workman³

et al. 2022

eClinicalMedicine

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Section: Discussioncontrasting

confidence: 42%

Section: Introductionmentioning

confidence: 99%

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

Zar¹,

MacGinty²,

Workman³

et al. 2022

eClinicalMedicine

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“…In our study, responses to either one or two doses of BNT162b2 in seropositive individuals were greater than those seen in naïve vaccinees and a second dose in a naturally infected individual was not associated with the expected increase in IgG. It is also now well recognized that vaccination following natural exposure is associated with great vaccine effectiveness 13-15 compared to either natural or vaccine induced immunity alone. As suggested by our study the greater effectiveness of hybrid immunity is likely linked to enhanced immunogenicity of vaccine on the background of natural immunity and the reported increase in the breadth of immunity.…”

Section: Discussioncontrasting

confidence: 42%

Natural and hybrid immunity following four COVID-19 waves in a South African cohort

Zar

MacGinty

Workman

et al. 2022

Preprint

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BackgroundMore than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity.MethodsA prospective cohort study in a South African community through the ancestral/beta/delta/omicron SARS-CoV-2 waves. Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG). To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults.FindingsDespite little disease, 176/339 (51·9%) participants were seropositive following wave 1, rising to 74%, 89·8% and 97·3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and the least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naïve vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave.InterpretationNaturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naïve vaccinee and thus may provide adequate protection.FundingUK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466]. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z).Research in contextEvidence before this studyNatural infection with ancestral SARS-CoV-2 virus provides partial protection against re-infection with the same and closely related SARS-CoV-2 variants, but higher rates of re-infection have been described with Omicron. In addition, vaccination against SARS-CoV2 provides relatively lower protection against symptomatic Omicron infection than for other variants. Hybrid immunity, a combination of immunity induced by natural infection and vaccination is of critical interest due to the high incidence of natural infection in many populations and increased availability of vaccination. Vaccination following infection may provide more robust immunity than either infection or vaccination alone, but there are limited data on the impact of hybrid immunity for protection against different variants or on the optimal vaccination strategy following natural infection.Added value of this studyWe leveraged a unique South African birth cohort in a poor peri-urban area, to longitudinally investigate infection, illness and serological responses to natural exposure to SARS-CoV-2 over 4 waves of the pandemic in healthy mothers. We also investigated the impact of prior natural exposure on BNT162b2 mRNA vaccine responses. We used this information to derive estimates of levels of spike-specific IgG associated with protection for subsequent infection following natural or hybrid immunity. Despite little disease, most participants were seropositive with rates rising from 52% to 74%, 90% and 97% after waves 1, 2, 3 and 4 respectively. Antibodies to spike protein induced by natural exposure protected against subsequent infection with the greatest protection for beta and the least for omicron. Antibody levels following vaccination were significantly higher in those who were seropositive prior to vaccine, compared to those seronegative. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% following 1 vaccine dose, 63% following 2 doses and only 11% in unvaccinated during the omicron wave. In those seropositive prior to vaccination no significant increase in antibody levels occurred after the 2nd dose of vaccine, unlike the increase in seronegative participants. A single dose of vaccine in seropositive individuals induced higher antibody concentrations than two doses in seronegative recipients.Implications of all the available evidenceNaturally induced spike antibodies do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior natural immunity is more immunogenic than 2 doses in seronegative people and may provide adequate protection against omicron and other variants. Vaccination programs in populations with high seroprevalence using a single vaccination as a primary strategy should be considered.

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“…Of the 3282 papers initially retrieved, we included 91 cohort studies evaluating the onset of reinfection, severe and very severe/lethal COVID‐19 among 15,034,624 previously infected subjects (Figure 1), either among health care workers (27 publications; n = 37,598 2,8,9,15,17,24,36,38,42–59 ) or in the general population (67 publications; n = 14,997,026 3–7,10,12,16–23,25–27,43,49,60–106 ).…”

Section: Resultsmentioning

confidence: 99%

Risk of reinfection and disease after SARS‐CoV‐2 primary infection: Meta‐analysis

Flacco

Martellucci

Baccolini³

et al. 2022

Eur J Clin Investigation

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Introduction A precise estimate of the frequency and severity of SARS‐CoV‐2 reinfections would be critical to optimize restriction and vaccination policies for the hundreds of millions previously infected subjects. We performed a meta‐analysis to evaluate the risk of reinfection and COVID‐19 following primary infection. Methods We searched MedLine, Scopus and preprint repositories for cohort studies evaluating the onset of new infections among baseline SARS‐CoV‐2‐positive subjects. Random‐effect meta‐analyses of proportions were stratified by gender, exposure risk, vaccination status, viral strain, time between episodes, and reinfection definition. Results Ninety‐one studies, enrolling 15,034,624 subjects, were included. Overall, 158,478 reinfections were recorded, corresponding to a pooled rate of 0.97% (95% CI: 0.71%–1.27%), with no substantial differences by definition criteria, exposure risk or gender. Reinfection rates were still 0.66% after ≥12 months from first infection, and the risk was substantially lower among vaccinated subjects (0.32% vs. 0.74% for unvaccinated individuals). During the first 3 months of Omicron wave, the reinfection rates reached 3.31%. Overall rates of severe/lethal COVID‐19 were very low (2–7 per 10,000 subjects according to definition criteria) and were not affected by strain predominance. Conclusions A strong natural immunity follows the primary infection and may last for more than one year, suggesting that the risk and health care needs of recovered subjects might be limited. Although the reinfection rates considerably increased during the Omicron wave, the risk of a secondary severe or lethal disease remained very low. The risk–benefit profile of multiple vaccine doses for this subset of population needs to be carefully evaluated.

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Impact of previous exposure to SARS-CoV-2 and of S-Trimer (SCB-2019) COVID-19 vaccination on the risk of reinfection: a randomised, double-blinded, placebo-controlled, phase 2 and 3 trial

Cited by 17 publications

References 26 publications

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

Natural and hybrid immunity following four COVID-19 waves in a South African cohort

Risk of reinfection and disease after SARS‐CoV‐2 primary infection: Meta‐analysis

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