Effectiveness of a fourth dose of mRNA-1273 against COVID-19 among older adults in the United States: Interim results from an observational cohort study

We evaluated relative vaccine effectiveness (rVE) of 4- vs. 3-dose mRNA-1273 against SARS-CoV-2 infection, and COVID-19 hospitalization and death in immunocompetent adults aged ≥50 years at Kaiser Permanente Southern California. We included 178,492 individuals who received a fourth dose of mRNA-1273, and 178,492 randomly selected 3-dose recipients who were matched to 4-dose recipients by age, sex, race/ethnicity, and third dose date. Adjusted 4- vs. 3-dose rVE against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospitalization death were 25.9 % (23.5 %, 28.2 %), 67.3 % (58.7 %, 74.1 %), and 72.5 % (-35.9 %, 95.2 %), respectively. Adjusted rVE against SARS-CoV-2 infection ranged between 19.8 % and 39.1 % across subgroups. Adjusted rVE against SARS-CoV-2 infection and COVID-19 hospitalization decreased 2–4 months after the fourth dose. Four mRNA-1273 doses provided significant protection against COVID-19 outcomes compared with 3 doses, consistent in various subgroups of demographic and clinical characteristics, although rVE varied and waned over time.     

Comparative effectiveness of four COVID-19 vaccines,BNT162b2 mRNA,mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection

BackgroundThere is limited data directly comparing the effectiveness of different COVID-19 vaccines.MethodsWe compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14–63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other characteristics.ResultsAs a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82–1.30), 1.19 (0.95–1.49), 1.70 (1.46–1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00–1.04), 1.20 (1.10–1.32), 1.39 (1.20–1.60).ConclusionsOur findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.     

Vaccine effectiveness of the mRNA-1273 3-dose primary series against COVID-19 in an immunocompromised population: A prospective observational cohort study

BackgroundData on the effectiveness of the 3-dose mRNA-1273 primary series are limited, particularly in comparison to 2 doses. Given suboptimal COVID-19 vaccine uptake among immunocompromised populations, it is important to monitor the effectiveness of fewer than the recommended doses in this population.MethodsWe conducted a matched cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of the 3-dose series vs 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 outcomes among immunocompromised individuals.ResultsWe included 21,942 3-dose recipients who were 1:1 matched with randomly selected 2-dose recipients (third doses accrued 08/12/2021–12/31/2021, with follow-up through 01/31/2022). Adjusted rVE of 3 vs 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0 % (95 % CI: 50.8–58.9 %), 83.0 % (75.4–88.3 %), and 87.1 % (30.6–97.6 %), respectively.ConclusionThree doses of mRNA-1273 were associated with a significantly higher rVE against SARS-CoV-2 infection and severe outcomes, compared to 2 doses. These findings were consistent across subgroups of demographic and clinical characteristics, and mostly consistent across subgroups of immunocompromising conditions. Our study highlights the importance of completing the 3-dose series for immunocompromised populations.     

Protection from Omicron Infection in Residents of Nursing and Retirement Homes in Ontario,Canada

ObjectivesTo identify factors that contribute to protection from infection with the Omicron variant of SARS-CoV-2 in older adults in nursing and retirement homes.DesignLongitudinal cohort study with retrospective analysis of infection risk.Setting and Participants997 residents of nursing and retirement homes from Ontario, Canada, in the COVID in LTC study.MethodsResidents with 3 messenger RNA (mRNA) dose vaccinations were included in the study. SARS-CoV-2 infection was determined by positive nasopharyngeal polymerase chain reaction test and/or circulating antinucleocapsid IgG antibodies. Cumulative probability of Omicron infection after recent COVID-19 was assessed by log-rank test of Kaplan-Meier curves. Cox regression was used to assess risk of Omicron infection by age, sex, mRNA vaccine combination, whether individuals received a fourth dose, as well as recent COVID-19.ResultsIn total, 171 residents (17.2%) had a presumed Omicron variant SARS-CoV-2 infection between December 15, 2021 (local start of the first Omicron wave) and May 3, 2022. Risk of Omicron infection was not different by age [hazard ratio (95% confidence interval) 1.01 (0.99‒1.02)], or in women compared with men [0.97 (0.70‒1.34)], but infection risk decreased 47% with 3 vaccine doses of mRNA-1273 (Moderna) compared with BNT162b2 (Pfizer) [0.53 (0.31-0.90)], 81% with any fourth mRNA vaccine dose [0.19 (0.12‒0.30)], and 48% with SARS-CoV-2 infection in the 3 months prior to beginning of the Omicron wave [0.52, (0.27‒0.99)].Conclusions and ImplicationsVaccine type (ie, mRNA-1273/Spikevax vs BNT162b2/Cominarty), any fourth vaccine dose, and hybrid immunity from recent COVID-19, were protective against infection with the Omicron variant. These data emphasize the importance of vaccine type, and number of vaccine doses, in maintenance of protective immunity and reduction of risk of Omicron variant breakthrough infection. These findings promote continued public health efforts to support vaccination programs and monitor vaccine immunogenicity in older adults.     

Relative effectiveness of booster vs. 2-dose mRNA Covid-19 vaccination in the Veterans Health Administration: Self-controlled risk interval analysis

ObjectiveTo estimate relative effectiveness of the booster mRNA Covid-19 vaccination versus the 2-dose primary series for both Delta and Omicron variants with self-controlled study design.MethodsWe used the Veterans Health Administration (VHA) Corporate Data Warehouse to identify U.S. Veterans who received the 2-dose primary mRNA Covid-19 vaccine series and a mRNA Covid-19 booster, and who had a positive SARS-CoV-2 test during the Delta (9/23/2021–11/30/2021) or Omicron (1/1/22–3/19/22) predominant period. Among them, we conducted a self-controlled risk interval (SCRI) analysis to compare odds of SARS-CoV-2 infection during a booster exposure interval versus a control interval. Exposures were a control interval (days 4–6 post-booster vaccination, presumably prior to gain of booster immunity), and booster exposure interval (days 14–16 post-booster vaccination, presumably following gain of booster immunity). Cases had a positive PCR or antigen SARS-CoV-2 test. Separately for Delta and Omicron periods, we used conditional logistic regression to calculate odds ratios (OR) of a positive test for the booster versus control interval and calculated relative effectiveness of booster versus 2-dose primary series as (1-OR)*100. The SCRI approach implicitly controlled for time-fixed confounders.ResultsWe found 42 individuals with a positive SARS-CoV-2 test in the control interval and 14 in the booster exposure interval during the Delta period, and 141 and 70, respectively, in the Omicron period. For the booster versus 2-dose primary series, the odds of infection were 70% (95 %CI: 42%, 84%) lower during the Delta period and 54% (95 %CI: 38%, 66%) lower during Omicron. In sensitivity analyses among those with prior Covid-19 history, and age stratification, ORs were similar to the main analysis.ConclusionsBooster vaccination was more effective relative to a 2-dose primary series during the Delta and Omicron predominant periods, and the relative effectiveness was consistent across age groups.     

Immunogenicity of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in SARS-CoV-2-naïve and exposed individuals in a phase 2/3, double-blind,randomized study

BackgroundWe evaluated immunogenicity of SCB-2019, a subunit vaccine candidate containing a pre-fusion trimeric form of the SARS-CoV-2 spike (S)-protein adjuvanted with CpG-1018/alum.MethodsThe phase 2/3, double-blind, randomized SPECTRA trial was conducted in five countries in participants aged ≥ 18 years, either SARS-CoV-2-naïve or previously exposed. Participants were randomly assigned to receive two doses of SCB-2019 or placebo administered intramuscularly 21 days apart. In the phase 2 part of the study, on days 1, 22, and 36, neutralizing antibodies were measured by pseudovirus and wild-type virus neutralization assays to SARS-CoV-2 prototype and variants, and ACE2-receptor-binding antibodies and SCB-2019–binding antibodies were measured by ELISA. Cell-mediated immunity was measured by intracellular cytokine staining via flow cytometry.Results1601 individuals were enrolled between 24 March and 13 September 2021 and received at least one vaccine dose. Immunogenicity analysis was conducted in a phase 2 subset of 691 participants, including 428 SARS-CoV-2-naïve (381 vaccine and 47 placebo recipients) and 263 SARS-CoV-2-exposed (235 vaccine and 28 placebo recipients). In SARS-CoV-2-naïve participants, GMTs of neutralizing antibodies against prototype virus increased 2 weeks post-second dose (day 36) compared to baseline (224 vs 12.7 IU/mL). Seroconversion rate was 82.5 %. In SARS-CoV-2-exposed participants, one SCB-2019 dose increased GMT of neutralizing antibodies by 48.3-fold (1276.1 IU/mL on day 22) compared to baseline. Seroconversion rate was 92.4 %. Increase was marginal post-second dose. SCB-2019 also showed cross-neutralization capability against nine variants, including Omicron, in SARS-CoV-2-exposed participants at day 36. SCB-2019 stimulated Th1-biased cell-mediated immunity to the S-protein in both naïve and exposed participants. The vaccine was well tolerated, no safety concerns were raised from the study.ConclusionsA single dose of SCB-2019 was immunogenic in SARS-CoV-2-exposed individuals, whereas two doses were required to induce immune response in SARS-CoV-2-naïve individuals. SCB-2019 elicited a cross-neutralizing response against emergent SARS-CoV-2 variants at antibody levels associated with clinical protection, underlining its potential as a booster.Clinicaltrials.gov: NCT04672395; EudraCT: 2020-004272-17.     

Robust immunogenicity of a third BNT162b2 vaccination against SARS-CoV-2 Omicron variant in a naïve New Zealand cohort

The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naïve at the time they were boosted. This adult cohort of 298 participants, oversampled for at-risk populations, was composed of 29% Māori and 28% Pacific peoples, with 40% of the population aged 55+. A significant proportion of the cohort was obese and presented with at least one comorbidity. Sera were collected 28 days and 6 months post second vaccination and 28 days post third vaccination. SARS-CoV-2 anti-S IgG titres and neutralising capacity using surrogate viral neutralisation assays against variants of concern, including Omicron BA.1, were investigated. The incidence of SARS-CoV-2 infection, within our cohort, prior to third vaccination was very low (<6%). This study found a third vaccine significantly increased the mean SARS-CoV-2 anti-S IgG titres, for every demographic subgroup, by a minimum of 1.5-fold compared to titres after two doses. Diabetic participants experienced a greater increase (∼4-fold) in antibody titres after their third vaccination, compared to non-diabetics (increase of ∼ 2-fold). This corrected for the deficiency in antibody titres within diabetic participants which was observed following two doses. A third dose also induced a neutralising response against Omicron variant BA.1, which was absent after two doses. This neutralising response improved regardless of age, BMI, ethnicity, or diabetes status. Participants aged ≥75 years consistently had the lowest SARS-CoV-2 anti-S IgG titres at each timepoint, however experienced the greatest improvement after three doses compared to younger participants. This study shows that in the absence of prior SARS-CoV-2 infection, a third Pfizer-BioNTech BNT162b2 vaccine enhances immunogenicity, including against Omicron BA.1, in a cohort representative of at-risk groups in the adult New Zealand population.     

Cellular and humoral immune responses after a third dose of SARS-CoV-2 mRNA vaccine in lung transplant recipients in Japan

BackgroundLung transplant (LTx) recipients are at higher risk of infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). There is an increasing demand for additional analysis regarding the efficacy and safety of after the initial series of mRNA SARS-CoV-2 vaccines in Japanese transplant recipients.MethodIn this open-label, nonrandomized prospective study carried out at Tohoku University Hospital, Sendai, Japan, LTx recipients and controls received third doses of either the BNT162b2 or the mRNA-1273 vaccine, and the cellular and humoral immune responses were analyzed.ResultsA cohort of 39 LTx recipients and 38 controls participated in the study. The third dose of SARS-CoV-2 vaccine promoted much greater humoral responses at 53.9 % of LTx recipients than after the initial series at 28.2 % of patients without increasing the risk of adverse events. However, still fewer LTx recipients responded to the SARS-CoV-2 spike protein with the median IgG titer of 129.8 AU/mL and with the median IFN-γ level of 0.01 IU/mL when compared to controls with those of 7394 AU/mL and 0.70 IU/mL, respectively.ConclusionAlthough the third dose of mRNA vaccine in LTx recipients was effective and safe, impaired cellular and humoral responses to SARS-CoV-2 spike protein were noted. Given lower antibody production and establishing vaccine safety, repeating the administration of mRNA vaccine will lead to robust protection in such a high-risk population (jRCT1021210009).     

Neutralizing antibody responses in healthcare personnel after three doses of mRNA BNT162b2 vaccine and association with baseline characteristics and past SARS-CoV-2 infection

AimTo estimate neutralizing antibody (NAb) immunity against SARS-CoV-2 in 739 healthcare personnel (HCP) vaccinated with three doses of BNT162b2 mRNA vaccine.MethodsSerum samples were collected at 3, 6, and 9 months after the second vaccine dose and at 7–55 days after the third dose. Samples were tested for NAbs against SARS-CoV-2 receptor binding domain.ResultsThe mean inhibition rates at 3, 6, and 9 months after the second dose were 86.33%, 73.38%, and 61.18%, and increased to 95.57% after the booster dose. Younger HCP and HCP with past SARS-CoV-2 infection had higher inhibition rates while there was an inverse correlation between NAb levels and comorbidities or tobacco use (p-values < 0.001). Increased NAb titers were also noticed in women (p-value = 0.033), especially at the end of the 9-month study period.ConclusionNAb levels increased considerably after a booster mRNA vaccine dose. Host factors and past SARS-CoV-2 infection influence NAb titers.     

Vaccine Effectiveness,School Reopening,and Risk of Omicron Infection Among Adolescents Aged 12–17 Years

PurposeThe BNT162b2 (Pfizer-BioNTech) is approved for adolescents aged 12–17 years. We estimated BNT162b2 vaccine effectiveness (VE) and a booster dose effectiveness in adolescents aged 12–17 years and the impact of opening schools and the Omicron variant on risk of SARS-CoV-2 infection in adolescents.MethodsWe used logistic regression with a test-negative design controlling for gender and race to estimate BNT162b2 VE and the effectiveness of a booster dose in adolescents aged 12–17 years. To evaluate the effect of school opening on Omicron transmission, we used Cox proportional hazards regression to compare adolescents to a reference group of adults aged 22–33 or aged 65+ years, investigating whether risk for adolescents increased relative to the reference group after school opened.ResultsWe found that adolescents who received two BNT162b2 doses had significant protection against Omicron infection in the first three months following their second dose (VE = 54.5%, confidence interval [CI]: [17.8%–76.9%], p = .014) but no protection afterwards. Receiving a booster dose was associated with lower risk of infection (odds ratio = 0.48, CI: [0.33–0.69], p < .0001) and restored efficacy to a similar level (VE = 56.3%, CI: [36.5%–70.6%], p < .0001). We observed a statistically significant increase (p = .04) in adolescent infection risk relative to adults in the period of Omicron predominance.DiscussionThe BNT162b2 vaccine is effective at preventing SARS-CoV-2 infection in adolescents but immunity against Omicron wanes rapidly and booster doses are needed to retain protection. More research is needed to determine the effect of school reopening on spread in the Omicron-dominant period.     

Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting

BackgroundIt is critical to monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups.MethodsWe conducted a retrospective study in patients ≥12 years who underwent testing for SARS-CoV-2 virus from April 14 through October 25, 2021, at urgent care centers in the New York metropolitan area. Patients self-reported vaccination status at the time of testing. We used a test-negative design to estimate vaccine effectiveness (VE) by comparing odds of a positive test for SARS-CoV-2 infection among vaccinated (n = 474,805), partially vaccinated (n = 87,834), and unvaccinated (n = 369,333) patients, adjusted for demographic factors and calendar time.ResultsVE against symptomatic infection after 2 doses of mRNA vaccine was 96% (95% Confidence Interval: 95%, 97%) in the pre-delta period and reduced to 79% (95% CI: 77%, 81%) in the delta period. In the delta period, VE for 12–15-year-olds (85%; [95% CI: 81%, 88%]) was higher compared to older age groups (<65% for all other age groups). VE estimates did not differ by sex and race/ethnicity. VE against symptomatic infection was the highest for individuals with a prior infection followed by full vaccination. VE against symptomatic infection after the 2-dose mRNA-1273 vaccine (82% [95% CI: 80%, 84%]) was higher compared to the BNT162b2 vaccine (76% [95% CI: 74%, 78%]) in the delta period. VE after 1-dose of the Ad26.COV2.S vaccine was the lowest compared to other vaccines (19% [95% CI: 15%, 23%]) in the delta period.ConclusionsVE against infection after two doses of the mRNA vaccines was high initially, but significantly reduced against the delta variant for both FDA-approved vaccines.     

Neutralization of Omicron subvariants BA.1 and BA.5 by a booster dose of COVID-19 mRNA vaccine in a Japanese nursing home cohort

The sustained epidemic of Omicron subvariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide concern, and older adults are at high risk. We conducted a prospective cohort study to assess the immunogenicity of COVID-19 mRNA vaccines (BNT162b2 or mRNA-1273) in nursing home residents and staff between May 2021 and December 2022. A total of 335 SARS-CoV-2 naïve individuals, including 141 residents (median age: 88 years) and 194 staff (median age: 44 years) participated. Receptor-binding domain (RBD) and nucleocapsid (N) protein IgG and neutralizing titer (NT) against the Wuhan strain, Alpha and Delta variants, and Omicron BA.1 and BA.5 subvariants were measured in serum samples drawn from participants after the second and third doses of mRNA vaccine using SARS-CoV-2 pseudotyped virus. Breakthrough infection (BTI) was confirmed by a notification of COVID-19 or a positive anti-N IgG result in serum after mRNA vaccination. Fifty-one participants experienced SARS-CoV-2 BTI during the study period. The RBD IgG and NTs against Omicron BA.1 and BA.5 were markedly increased in SARS CoV-2 naïve participants 2 months after the third dose of mRNA vaccine, compared to those 5 months after the second dose, and declined 5 months after the third dose. The decline in RBD IgG and NT against Omicron BA.1 and BA.5 in SARS-CoV-2 naïve participants after the second and the third dose was particularly marked in those aged ≥ 80 years. BTIs during the BA.5 epidemic period, which occurred between 2 and 5 months after the third dose, induced a robust NT against BA.5 even five months after the booster dose vaccination. Further studies are required to assess the sustainability of NTs elicited by Omicron-containing bivalent mRNA booster vaccine in older adults.     

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy: A retrospective matched cohort study

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged ≥ 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants.We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 – risk ratio)X100.Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14–118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2–20.2]. RVE decreased from 28.5 % (95 % CI: 24.7–32.1) in the time-interval 14–28 days to 7.6 % (95 % CI: ?14.1 to 18.3) in the time-interval 56–118 days. However, RVE against severe COVID-19 was higher (34.0 %, 95 % CI: 23.4–42.7), decreasing from 43.2 % (95 % CI: 30.6–54.9) to 27.2 % (95 % CI: 8.3–42.9) over the same time span.Although RVE against SARS-CoV-2 infection was much reduced 2–4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated.     

Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France

The emergence of SARS-CoV-2 variants calls for continuous monitoring of vaccine effectiveness (VE). We estimated the absolute effectiveness of complete 2-dose primary vaccination and booster vaccination with COVID-19 mRNA vaccines, and the duration of protection against Delta and Omicron BA.1 symptomatic infection and severe outcomes. French residents aged ≥50 years, who presented with SARS-CoV-2-like symptoms and tested for SARS-CoV-2 between June 6, 2021 and February 10, 2022 were included. A test-negative study was conducted to estimate VE against symptomatic infection, using conditional logistic regression models. Cox proportional hazard regressions were performed to assess additional protection against severe COVID-19 outcomes (any hospitalization, and intensive care units [ICU] admission or in-hospital death). In total, 273 732 cases and 735 919 controls were included. VE against symptomatic infection after 2-doses vaccination was 86% (95% CI: 75–92%) for Delta and 70% (58–79%) for Omicron, 7–30 days post vaccination. Protection waned over time, reaching 60% (57–63%) against Delta and 20% (16.–24%) for Omicron BA.1 > 120 days after vaccination. The booster dose fully restored protection against symtpomatic Delta infection (95% [81–99%]) but only partially against symptomatic Omicron BA.1 infection (63% [59–67%]). VE against Delta-related severe outcomes was above 95% with 2 doses, and persisted for at least four months. Protection against any Omicron BA.1-hospitalization was 92% (65%-99%) at 8–30 days, and 82% (67%-91%) > 120 days from the second dose. Against BA.1 ICU admission or in-patient death, VE stood at 98% (0–100%) at 8–30 days, and was 90% (40–99%) > 120 days from the second dose. Protection confered by mRNA vaccines against severe disease caused by either Delta or Omicron BA.1 appeared high and sustained over time. Protection against symptomatic diseases after 2 doses decreased rapidly, especially against Omicron BA.1. A booster dose restored high protection against Delta but only a partial one against Omicron BA.1.     

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination.A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44–0.88 log₁₀ higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55–1.77 for IgG, 1.00–1.78 for live virus nAb and 1.79–2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.     

Impact of prior SARS-CoV-2 infection on incidence of hospitalization and adverse events following mRNA SARS-CoV-2 vaccination: A nationwide,retrospective cohort study

BackgroundPrevious studies evaluated the SARS-CoV-2 vaccine safety or compared adverse events following vaccination to those from infection. Limited data about the impact of prior infection on post-vaccine adverse events are available. The objective of this study was to evaluate the impact of prior SARS-CoV-2 infection on outcomes shortly after vaccination using a longitudinal design.MethodsNationwide, multicenter, retrospective cohort study of hospitalization, death, and pre-specified adverse event rates among Veterans who received mRNA vaccines within the Veterans Health Administration between 12/11/2020 and 8/31/2021. Daily incidence rates were compared before and after vaccine doses, stratified by history of microbiologically-confirmed SARS-CoV-2.Results3,118,802 patients received a first dose and 2,979,326 a second, including 102,829 with a history of SARS-CoV-2 infection. Daily incident hospitalization rates were unchanged before and after the second dose among patients without previous infection (28.8/100,000 post-dose versus 28.6/100,000 pre-dose, p = 0.92). In previously-infected patients, the hospitalization rate increased above baseline one day following vaccination (158.2/100,000 after dose 2 versus 57.3/100,000 pre-dose, p < 0.001), then returned to baseline. Chart review indicated vaccine side effects, such as fever, constitutional symptoms, weakness, or falls, as the definite (39%) or possible (18%) cause of hospitalization. Affected patients had mean age 75, and 90% had at least one serious comorbidity. Hospitalizations were brief (median 2 days), with rapid return to baseline health. Worse baseline health among previously-infected patients prevented conclusions about mortality risk.ConclusionsTwo-dose mRNA vaccine regimens are safe in a population with many comorbidities. Transient increased risks of hospitalization were identified among patients with prior SARS-CoV-2, absolute risk ～1:1000. Findings support additional study regarding the optimal dosing schedule in this population.FundingNone.     

Association between history of SARS-CoV-2 infection and severe systemic adverse events after mRNA COVID-19 vaccination among U.S. adults

BackgroundRisk of experiencing a systemic adverse event (AE) after mRNA coronavirus disease 2019 (COVID-19) vaccination may be greater among persons with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; data on serious events are limited. We assessed if adults reporting systemic AEs resulting in emergency department visits or hospitalizations during days 0–7 after mRNA COVID-19 vaccine dose 1 were more likely to have a history of prior SARS-CoV-2 infection compared with persons who reported no or non-severe systemic AEs.MethodsWe conducted a nested case-control study using v-safe surveillance data. Participants were ≥ 18 years and received dose 1 during December 14, 2020─May 9, 2021. Cases reported severe systemic AEs 0–7 days after vaccination. Three controls were frequency matched per case by age, vaccination date, and days since vaccination. Follow-up surveys collected SARS-CoV-2 histories.ResultsFollow-up survey response rates were 38.6 % (potential cases) and 56.8 % (potential controls). In multivariable analyses including 3,862 case-patients and 11,586 controls, the odds of experiencing a severe systemic AE were 2.4 (Moderna, mRNA-1273; 95 % confidence interval [CI]: 1.89, 3.09) and 1.5 (Pfizer-BioNTech, BNT162b2; 95 % CI: 1.17, 2.02) times higher among participants with pre-vaccination SARS-CoV-2 histories compared with those without. Medical attention of any kind for symptoms during days 0–7 following dose 2 was not common among case-patients or controls.ConclusionsHistory of SARS-CoV-2 infection was significantly associated with severe systemic AEs following dose 1 of mRNA COVID-19 vaccine; the effect varied by vaccine received. Most participants who experienced severe systemic AEs following dose 1 did not require medical attention of any kind for symptoms following dose 2. Vaccine providers can use these findings to counsel patients who had pre-vaccination SARS-CoV-2 infection histories, experienced severe systemic AEs following dose 1, and are considering not receiving additional mRNA COVID-19 vaccine doses.     

Six-month safety follow-up of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in adults: A phase 2/3, double-blind,randomized study

BackgroundWe evaluated the safety of SCB-2019, a protein subunit vaccine candidate containing a recombinant SARS-CoV-2 spike (S) trimer fusion protein, combined with CpG-1018/alum adjuvants.MethodsThis ongoing phase 2/3, double-blind, placebo-controlled, randomized trial is being conducted in Belgium, Brazil, Colombia, the Philippines, and South Africa in participants ≥ 12 years of age. Participants were randomly assigned to receive 2 doses of SCB-2019 or placebo administered intramuscularly 21 days apart. Here, we present the safety results of SCB-2019 over the 6-month period following 2-dose primary vaccination series in all adult participants (≥18 years of age).ResultsA total of 30,137 adult participants received at least one dose of study vaccine (n = 15,070) or placebo (n = 15,067) between 24 March 2021 and 01 December 2021. Unsolicited adverse events, medically-attended adverse events, adverse events of special interest, and serious adverse events were reported in similar frequencies in both study arms over the 6-month follow-up period. Vaccine-related SAEs were reported by 4 of 15,070 SCB-2019 recipients (hypersensitivity reactions in two participants, Bell’s palsy, and spontaneous abortion) and 2 of 15,067 placebo recipients (COVID-19, pneumonia, and acute respiratory distress syndrome in one participant and spontaneous abortion in the other one). No signs of vaccine-associated enhanced disease were observed.ConclusionsSCB-2019 administered as a 2-dose series has an acceptable safety profile. No safety concerns were identified during the 6-month follow-up after the primary vaccination.Clinical Trials Registration: NCT04672395; EudraCT: 2020–004272-17.     

Number of COVID-19 hospitalisations averted by vaccination: Estimates for the Netherlands,January 6, 2021 through August 30, 2022

BackgroundVaccines against COVID-19 have proven effective in preventing COVID-19 hospitalisation. In this study, we aimed to quantify part of the public health impact of COVID-19 vaccination by estimating the number of averted hospitalisations. We present results from the beginning of the vaccination campaign (‘entire period’, January 6, 2021) and a subperiod starting at August 2, 2021 (‘subperiod’) when all adults had the opportunity to complete their primary series, both until August 30, 2022.MethodsUsing calendar-time specific vaccine effectiveness (VE) estimates and vaccine coverage (VC) by round (primary series, first booster and second booster) and the observed number of COVID-19 associated hospitalisations, we estimated the number of averted hospitalisations per age group for the two study periods. From January 25, 2022, when registration of the indication of hospitalisation started, hospitalisations not causally related to COVID-19 were excluded.ResultsIn the entire period, an estimated 98,170 (95 % confidence interval (CI) 96,123–99,928) hospitalisations were averted, of which 90,753 (95 % CI 88,790–92,531) were in the subperiod, representing 57.0 % and 67.9 % of all estimated hospital admissions. Estimated averted hospitalisations were lowest for 12–49-year-olds and highest for 70–79-year-olds. More admissions were averted in the Delta period (72.3 %) than in the Omicron period (63.4 %).ConclusionCOVID-19 vaccination prevented a large number of hospitalisations. Although the counterfactual of having had no vaccinations while maintaining the same public health measures is unrealistic, these findings underline the public health importance of the vaccination campaign to policy makers and the public.     

Immunogenicity of BNT162b2 COVID-19 vaccine in New Zealand adults

BackgroundThere is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease.MethodsThis prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for Māori, Pacific peoples, older adults ≥ 65 years of age, and those with co-morbidities. Serum samples were analysed at baseline and 28 days after second dose for presence of quantitative anti-S IgG by chemiluminescent microparticle immunoassay and for neutralizing capacity against Wuhan, Beta, Delta, and Omicron BA.1 strains using a surrogate viral neutralisation assay.Results285 adults with median age of 52 years were included. 55% were female, 30% were Māori, 28% were Pacific peoples, and 26% were ≥ 65 years of age. Obesity, cardiac and pulmonary disease and diabetes were more common than in the general population. All participants received 2 doses of BNT162b2 vaccine. At 28 days after second vaccination, 99.6% seroconverted to the vaccine, and anti-S IgG and neutralising antibody levels were high across gender and ethnic groups. IgG and neutralising responses declined with age. Lower responses were associated with age ≥ 75 and diabetes, but not BMI. The ability to neutralise the Omicron BA.1 variant in vitro was severely diminished but maintained against other variants of concern.ConclusionsVaccine antibody responses to BNT162b2 were generally robust and consistent with international data in this COVID-19 naïve cohort with representation of key populations at risk for COVID-19 morbidity. Subsequent data on response to boosters, durability of responses and cellular immune responses should be assessed with attention to elderly adults and diabetics.