Investigation of Vaccine Breakthrough Infections by Vaccine strategy during the Delta Variant Wave in France

Herein, we describe the characteristics of vaccine breakthrough infections (VBI) in fully vaccinated individuals according to five vaccine strategies during the Delta wave in France. Inclusion criterion was a positive test at least 2 weeks after a full vaccine schedule: homologous vaccination with Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273); heterologous vaccination with Astrazeneca and Pfizer-BioNTech (ChadOx1/BNT162b2); single-dose vaccines Johnson & Johnson (Ad26.COV2.S) or Astrazeneca (ChadOx1). A total of 1630 VBI from patients fully vaccinated between February and July were included in this study. SARS-CoV-2 sequencing performed for 1366 samples showed that the delta variant represented 94.1% (1286/1366). Delta-VBI were mainly symptomatic (mild symptoms) with no difference according to the vaccine strategy (p=0.362). The median RT-PCR Ct values at diagnosis were significantly different between symptomatic and asymptomatic cases only for BNT162b2 group (17.7 (15.07, 20.51) vs 19.00 (16.00, 23.00), p=0.004). Up to 50% of VBI was classified as early-VBI (infected less than one month after full immunization) for BNT162b2, mRNA-1273, ChadOx1, and J Ad26.COV2.S. People aged 14-49 yo were overrepresented in early VBI compared to non-early VBI for BNT162b2 and mRNA-1273 (73.92% vs 37.87% for BNT162b2 and 77.78% vs 46.67 % for mRNA-1273, p<0.05). Our data emphasize a high prevalence of Delta-VBI occurring only one month after full immunization in young patients that might be related to relaxation of barrier gestures.

Epidemiology of myocarditis and pericarditis following mRNA vaccines in Ontario, Canada: by vaccine product, schedule and interval

ImportanceIncreased rates of myocarditis/pericarditis following COVID-19 mRNA vaccines have been observed. However, little data are available related to product-specific differences, which have important programmatic impacts.ObjectiveThe objective of this study was to estimate reporting rates of myocarditis/pericarditis following COVID-19 mRNA vaccine by product, age, sex, and dose number, as well inter-dose interval.DesignWe conducted a population-based cohort study using passive vaccine safety surveillance data. All individuals in Ontario, Canada who received at least one dose of COVID-19 mRNA vaccine between December 14, 2020 and September 4, 2021 were included.SettingThis study was conducted in Ontario, Canada (population: 14.7 million) using the provincial COVID-19 vaccine registry and provincial adverse events following immunization database.ParticipantsWe included all individuals with a reported episode of myocarditis/pericarditis following COVID-19 vaccine in the study period. We obtained information on all doses administered in the province to calculate reporting rates.ExposureReceipt of COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]).Main Outcome(s) and Measure(s)Reported rate of myocarditis/pericarditis meeting level 1-3 of the Brighton Collaboration case definitions.ResultsThere were 19,740,741 doses of mRNA vaccines administered and 297 reports of myocarditis/pericarditis meeting our inclusion criteria. Among these, 69.7% occurred following the second dose of COVID-19 mRNA vaccine and 76.8% occurred in males. The median age of individuals with a reported event was 24 years. The highest reporting rate of myocarditis/pericarditis was observed in males aged 18-24 years following mRNA-1273 as the second dose; the rate in this age group was 5.1 (95% CI 1.9-15.5) times higher than the rate following BNT162b2 as the second dose. Overall reporting rates were higher when the inter-dose interval was shorter (i.e., ≤30 days) for both vaccine products. Among individuals who received mRNA-1273 for the second dose, rates were higher for those who had a heterologous as opposed to homologous vaccine schedule.Conclusions and RelevanceOur results suggest that vaccine product, inter-dose interval and vaccine schedule combinations may play a role in the risk of myocarditis/pericarditis, in addition to age and sex. Certain programmatic strategies could reduce the risk of myocarditis/pericarditis following mRNA vaccines.

Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50–89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14–35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65–84 days) compared with those vaccinated with a standard (19–29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14–35 days post dose 2 for BNT162b2 than AZD1222. For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.

Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients

Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 in a cohort of patients who were previously infected with SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of SARS-CoV-2 infection were enrolled in our immunological study. The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5 – 327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time depends on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers.

Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4–39.7) against Covid-19, 55.1% (95% CI, 46.6–62.2) against hospitalization, and 61.8% (95% CI, 48.9–71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2–84.2) against Covid-19, 87.6% (95% CI, 78.2–92.9) against hospitalization, and 93.6% (95% CI, 81.9–97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.

Physical activity associates with enhanced immunogenicity of an inactivated virus vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases

Immunocompromised individuals show lower vaccine immunogenicity, which may be modulated by physical activity. This prospective cohort study within a phase-4 vaccination trial investigated whether physical activity is associated with enhanced immunogenicity of Coronavac (SARS-CoV-2 inactivated vaccine) in patients with autoimmune rheumatic diseases (ARD) (n=898) and non-ARD (n=197) individuals without pre-existing immunogenicity to SARS-CoV-2 after receiving a two-dose vaccine schedule. Seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity were assessed. After controlling for covariates, active patients (≥150 min/week) exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary (≥150 min/week/<8h/day) vs. inactive/sedentary (<150 min/week/>8h/day) ARD. A dose-response was observed, with greater benefits for ≥350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4]; 41% [95%CI: 10-80%]; 35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD. A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised individuals.