Resilient T cell responses to B.1.1.529 (Omicron) SARS-CoV-2 variant

Emergence of the SARS-CoV-2 variant-of-concern (VOC) B.1.1.529 (Omicron) in late 2021 has raised alarm among scientific and health care communities due to a surprisingly large number of mutations in its spike protein. Public health surveillance indicates that the Omicron variant is significantly more contagious than the previously dominant VOC, B.1.617.2 (Delta). Several early reports demonstrated that Omicron exhibits a higher degree (~10-30-fold) of escape from antibody neutralization compared to earlier lineage variants. Therefore, it is critical to determine how well the second line of adaptive immunity, T cell memory, performs against Omicron in people following COVID-19 infection and/or vaccination. To that purpose, we analyzed a cohort (n=345 subjects) of two- or three- dose messenger RNA (mRNA) vaccine recipients and COVID-19 post infection subjects (including those receiving 2 doses of mRNA vaccine after infection), recruited to the CDC-sponsored AZ HEROES research study, alongside 32 pre-pandemic control samples. We report that T cell responses against Omicron spike peptides were largely preserved in all cohorts with established immune memory. IFN-gamma producing T cell responses remained equivalent to the response against the ancestral strain (WA1/2020), with some (<20%) loss in IL-2 single- or IL-2+IFN-gamma+ poly-functional responses. Three-dose vaccinated participants had similar responses to Omicron relative to convalescent or convalescent plus two-dose vaccinated groups and exhibited responses significantly higher than those receiving two mRNA vaccine doses. These results provide further evidence that a three-dose vaccine regimen benefits the induction of optimal functional T cell immune memory.

Emerging Socioeconomic Disparities in COVID-19 Vaccine Second-Dose Completion Rates in the United States

Although COVID-19 vaccination plans acknowledge a need for equity, disparities in two-dose vaccine initiation have been observed in the United States. We aim to assess if disparity patterns are emerging in COVID-19 vaccination completion. We gathered (n = 843,985) responses between February and November 2021 from a web survey. Individuals self-reported demographics and COVID-19 vaccination status. Dose initiation and completion rates were calculated incorporating survey weights. A multi-variate logistic regression assessed the association between income and completing vaccination, accounting for other demographics. Overall, 57.4% initiated COVID-19 vaccination, with 84.5% completing vaccination. Initiation varied by income, and we observed disparities in completion by occupation, race, age, and insurance. Accounting for demographics, higher incomes are more likely to complete vaccination than lower incomes. We observe disparities in completion across annual income. Differences in COVID-19 vaccination completion may lead to two tiers of protection in the population, with certain sub-groups being better protected from future infection.

Prevalence of SARS-CoV-2 Variants of Concern and Variants of Interest in COVID-19 Breakthrough Infections in a Hospital in Monterrey, Mexico

SARS-CoV-2 variants of concern (VOCs) or of interest (VOIs) causing vaccine breakthrough infections pose an increased risk to worldwide public health. An observational case-control study was performed of SARS-CoV-2 vaccine breakthrough infections in hospitalized or ambulatory patients in Monterrey, Mexico, from April through August 2021. Vaccination breakthrough was defined as a SARS-CoV-2 infection that occurred any time after 7 days of inoculation with partial (e.g., first dose of two-dose vaccines) or complete immunization (e.g., second dose of two-dose vaccines or single-dose vaccine, accordingly). Case group patients (n = 53) had partial or complete vaccination schemes with CanSino (45%), Sinovac (19%), Pfizer/BioNTech (15%), and AstraZeneca/Oxford (15%). CanSino was administered most frequently in ambulatory patients (p < 0.01). The control group (n = 19) received no COVID-19 vaccines. Among SARS-CoV-2 variants detected by whole-genome sequencing, VOC Delta B.1.617.2 predominated in vaccinated ambulatory patients (p < 0.01) and AY.4 in hospitalized patients (p = 0.04); VOI Mu B.1.621 was detected in four (7.55%) vaccinated patients. SARS-CoV-2 breakthrough infections in our hospital occurred mostly in patients vaccinated with CanSino due to the higher prevalence of CanSino vaccine administration in our population. These patients developed mild COVID-19 symptoms not requiring hospitalization. The significance of this study lies on the detection of SARS-CoV-2 variants compromising the efficacy of local immunization therapies in Monterrey, Mexico.

Immune responses to inactivated and vector-based vaccines in individuals previously infected with SARS-CoV-2

Immunity wanes in individuals previously infected with SARS-CoV-2, and vaccinating those individuals may help reduce reinfection. Herein, reactogenicity and immunogenicity following vaccination with inactivated (CoronaVac) and vector-based (ChAdOx1-S, AZD1222) vaccines were examined in previously infected individuals. Immune response was also compared between short and long intervals between first date of detection and vaccination. Adverse events were mild but were higher with AZD1222 than with CoronaVac. Baseline IgG-specific antibodies and neutralizing activity were significantly higher with shorter than longer intervals. With a single-dose vaccine, IgG and IgA-specific binding antibodies, neutralizing activity, and total interferon-gamma response peaked at 14 days. Immune response was significantly higher in recovered individuals than in infection-naïve individuals. Antibody response was greater with longer than shorter intervals. AZD1222 induced higher antibody and T cell responses than those of CoronaVac. Thus, to achieve immunity, individuals with prior SARS-CoV-2 exposure may require only a single dose of AZD1222 or two doses of CoronaVac to achieve the immune response. These findings supported vaccine strategies in previously infected individuals.

Effectiveness of CoronaVac, ChAdOx1, BNT162b2 and Ad26.COV2.S among individuals with prior SARS-CoV-2 infection in Brazil

Background. COVID-19 vaccines have proven highly effective among SARS-CoV-2 naive individuals, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with prior infection is less clear. Methods. Utilizing national COVID-19 notification, hospitalization, and vaccination datasets from Brazil, we performed a case-control study using a test-negative design to assess the effectiveness of four vaccines (CoronaVac, ChAdOx1, Ad26.COV2.S and BNT162b2) among individuals with laboratory-confirmed prior SARS-CoV-2 infection. We matched RT-PCR positive, symptomatic COVID-19 cases with RT-PCR-negative controls presenting with symptomatic illnesses, restricting both groups to tests performed at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity, and the odds of hospitalization or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. Findings. Among individuals with prior SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection ≥ 14 days from vaccine series completion was 39.4% (95% CI 36.1-42.6) for CoronaVac, 56.0% (95% CI 51.4-60.2) for ChAdOx1, 44.0% (95% CI 31.5-54.2) for Ad26.COV2.S, and 64.8% (95% CI 54.9-72.4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose compared with the first dose. Effectiveness against hospitalization or death ≥ 14 days from vaccine series completion was 81.3% (95% CI 75.3-85.8) for CoronaVac, 89.9% (95% CI 83.5-93.8) for ChAdOx1, 57.7% (95% CI -2.6-82.5) for Ad26.COV2.S, and 89.7% (95% CI 54.3-97.7) for BNT162b2.

Protection following BNT162b2 booster substantially exceeds that of a fresh 2-dose vaccine: a quasi-experimental study

Israel began administering a BNT162b2 booster dose to restore protection following the waning of the 2-dose vaccine. Biological studies have shown that a fresh booster leads to increased antibody levels compared to a fresh 2-dose vaccine, which may suggest increased effectiveness. To compare the real-world effectiveness of a fresh booster dose with that of a fresh 2-dose vaccine, we conduct a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age cutoff policies. Our analysis shows that a fresh booster increases protection against confirmed infection by 3.7 (95% CI: 2.7 to 5.2) fold compared to a fresh 2-dose vaccine.

Antibody Responses to 3rd Dose mRNA Vaccines in Nursing Home and Assisted Living Residents

A comparison of SARS-CoV-2 wild-type and the beta variant virus neutralization capacity between 2 and 3 mRNA vaccine series in nursing home residents, and between nursing home and assisted living residents strongly supports 3rd dose vaccine recommendations, and equivalent polices for nursing homes and assisted living settings. Findings suggest that residents mount a robust humoral response to a 3rd mRNA vaccination, and have greater neuralization capacity compared to a 2 dose series.

Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study

Objectives To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination. Design Test negative case-control study. Setting Kaiser Permanente Southern California (KPSC), an integrated healthcare system. Participants Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021. Interventions Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination. Main outcome measures Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1–odds ratio)×100%. Results The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta. Conclusions Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.

High correlation between binding IgG (anti-RBD/S) and neutralizing antibodies against SARS-CoV-2 six months after vaccination

Vaccination is considered the most important measure to control the COVID-19 pandemic. Extensive fol-low-up studies with distinct vaccines and populations are able to promote robust and reliable data to better understand the effectiveness of this pharmacologic strategy. In this sense, we present data regarding binding and neutralizing antibodies throughout time, from vaccinated and previously infected (PI) health care work-ers (HCW) in Portugal. We analyzed serum samples of 132 HCW, vaccinated and with previous SARS-CoV-2 infection. Samples were collected before vaccination (baseline, M1), at second dose vaccine uptake (M2), and 25-70 days (M3) and 150-210 days (M4) after the second dose for vaccinated individuals. The IgG (anti-RBD/S) antibody geometric mean titer found on vaccinated HCW at M2 (814.7 AU/ml; 95% CI 649.8-1021.5) were sig-nificantly higher than those found on PI HCW at recruitment (M1) (252.6 AU/ml; 95% CI 108.7 - 587.1), and the neutralizing antibodies (nAb) were similar between these groups, 93.2 UI/ml (95% CI 73.2- 118.5) vs. 84.1 UI/ml (95% CI 40.4-155.9), respectively. We detected about 10-fold higher IgG (anti-RBD/S) antibodies titers in M3 when compared with M2, with a slightly but significant decrease in titers from 36 days after the second dose vaccine uptake. The increase of nAb titers were correlated with IgG (anti-RBD/S) antibodies titers, how-ever, contrasting to IgG (anti-RBD/S) antibodies titers, we did not detect a decrease in nAb titer from 36 days after a second vaccine dose uptake. At M4, was observed a decrease of 8-fold in binding IgG (anti-RBD/S) and nAb. No significant differences in antibody titers were observed by sex, age or chronic diseases. Our results suggest that IgG (anti-RBD/S) antibodies titers and nAb titers could be correlated, but ongoing follow up of the cohort, is required to better understand this correlation, and the duration of the immune response.