COVID-19 vaccine effectiveness among healthcare workers: a hospital-based cohort study.

OBJECTIVES: Healthcare workers (HCWs) were the first to be prioritised for COVID-19 vaccination. This study aims to estimate the COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 symptomatic infection among HCWs in Portuguese hospitals. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We analysed data from HCWs (all professional categories) from three central hospitals: one in the Lisbon and Tagus Valley region and two in the central region of mainland Portugal, between December 2020 and March 2022. VE against symptomatic SARS-CoV-2 infection was estimated as one minus the confounder adjusted HRs by Cox models considering age group, sex, self-reported chronic disease and occupational exposure to patients diagnosed with COVID-19 as adjustment variables. RESULTS: During the 15 months of follow-up, the 3034 HCWs contributed a total of 3054 person-years at risk, and 581 SARS-CoV-2 events occurred. Most participants were already vaccinated with a booster dose (n=2653, 87%), some are vaccinated with only the primary scheme (n=369, 12.6%) and a few remained unvaccinated (n=12, 0.4%) at the end of the study period. VE against symptomatic infection was 63.6% (95% CI 22.6% to 82.9%) for HCWs vaccinated with two doses and 55.9% (95% CI -1.3% to 80.8%) for HCWs vaccinated with one booster dose. Point estimate VE was higher for individuals with two doses taken between 14 days and 98 days (VE=71.9%; 95% CI 32.3% to 88.3%). CONCLUSION: This cohort study found a high COVID-19 VE against symptomatic SARS-CoV-2 infection in Portuguese HCWs after vaccination with one booster dose, even after Omicron variant occurrence. The small sample size, the high vaccine coverage, the very low number of unvaccinated individuals and the few events observed during the study period contributed to the low precision of the estimates.

A single dose of COVID-19 vaccine induces a strong T cell and B cell response in healthcare professionals recovered from SARS-CoV-2 infection.

A broad understanding on how SARS-CoV-2 infection and vaccination mobilize the immune system is necessary to find the best predictors of long-term protection and identify individuals that would benefit from additional vaccine doses. This study aims to understand the effect of a single dose of Pfizer-BioNTech BNT162b2 COVID-19 vaccine, in individuals recovered from SARS-CoV-2 infection, on circulating CD4+ T follicular helper (Tfh)-cells, Spike-specific T-cells and IgG/IgA antibodies. For that, peripheral blood samples from 50 healthcare professionals, recovered from SARS-CoV-2 infection, collected immediately before (T1) and 15 days after (T2) vaccine administration, were used to analyze the frequency and numbers of Tfh-cells and their subsets, serum titers of SARS-CoV-2-specific antibodies, and SARS-CoV-2-specific T-cells. Six months after infection (T1), 96% of recovered participants presented either IgG or T-cells specific for Spike, however, Spike-specific T-cells were missing in 16% of them. These individuals presented lower levels of Spike-specific IgG (T1 and T2), IgA (T1), and Spike-specific T-cells (T2). Vaccination increased the percentage of participants reactive for Spike-specific T-cells (from 64 to 98%), IgG (from 90 to 100%) and IgA (from 48 to 98%). It also mobilized circulating Tfh-cells, increasing their frequency and activation, and promoting Tfh17 polarization, restoring the decreased numbers of Tfh-cells (especially Tfh17) observed in recovered participants. Interestingly, Tfh percentage correlated with Spike-specific IgG levels. Our data showed that a single dose of vaccine efficiently restored Spike-specific T-cells, and IgG and IgA antibodies. Mobilization of Tfh-cells, and their correlation with IgG levels, suggest that vaccination induced a functional Tfh cell response.

Long-term serological SARS-CoV-2 IgG kinetics following mRNA COVID-19 vaccine: real-world data from a large cohort of healthcare workers.

OBJECTIVES: This study aimed to assess kinetics and predictive variables of humoral immune response to mRNA SARS-CoV-2 vaccine administration. METHODS: We collected blood samples before (T0) and 15, 90, and 180 days after vaccination (T1, T2, and T3, respectively). The Quant SARS-CoV-2 Immunoglobulin (IgG) II Chemiluminescent Microparticle Immunoassay was used to determine anti-spike IgG. RESULTS: In almost 3000 healthcare-collected blood samples at the three time points, we found the following: at 15 days postvaccination, 97.6% of subjects presented a robust IgG anti-spike response (>4160 AU/ml); then, at three and six months, it decreased in median 6.5-fold to 35.0% and 3.0-fold to 3.3%, respectively. A linear mixed-effects model supported that female gender, younger age groups, and being seropositive prevaccination maintained higher antibody titers. Curves became tighter with time progression, although titers from seropositive subjects decrease at a slower rate than seronegative ones. CONCLUSION: These findings strengthen the case for a steep decrease of anti-SARS-CoV-2 antibodies up to six months, suggesting that serological evaluation might guide the need for periodic booster vaccinations in specific groups prone to lower antibody titers.

The type of SARS-CoV-2 vaccine influences serological response in kidney transplant recipients.

Vaccination is a promising strategy to control the ongoing pandemic; however, solid organ recipients tend to develop a weaker immune response to vaccination. Anti-spike SARS-CoV-2 antibodies titers were measured 2-4 weeks post-vaccination completion in 131 KT patients without previous infection. Demographic, clinical, and laboratorial parameters were analyzed to identify which factors contributed to seroconversion. Factors that influenced seroconversion, that occurred in 76 patients (58%), were longer time post-transplant, immunosuppression without an antiproliferative drug and vaccination with mRNA vaccines. Patients who received mRNA vaccines had significantly higher rates of seroconversion compared with adenovirus vector vaccines (67% vs 33%, P < .001) and higher anti-spike IgG titers. These findings reinforce the need to discuss the vaccination strategy in this population, including a third dose with a mRNA vaccine.

Humoral response to the SARS-CoV-2 BNT162b2 mRNA vaccine: Real-world data from a large cohort of healthcare workers.

BACKGROUND: The SARS-CoV-2 pandemic was responsible for the death of millions of people around the world, which accelerated the study of vaccines. The BNT162b2 mRNA COVID-19 is a messenger RNA vaccine that encodes the spike protein of the virus. However, the duration of the protection conferred by this vaccine and factors associated with immune responses require validation in large cohorts. METHODS: Here, we present data of humoral immune response to vaccination in4264 healthcare workers, tested before (T0) and 15 and 90 days (T1 and T2, respectively) following vaccination.Peripheral blood was collected for immunological analysis using the Quant SARS-CoV-2 IgG II Chemiluminescent Microparticle Immunoassay (CMIA) to determine anti-spike IgG, receptor binding domain (RBD), S1 subunit of SARS-CoV-2. FINDINGS: At T0, 96·8% (n = 4129) of participants had IgG antibodies non-reactive to anti-SARS-CoV-2. Fifteen days after completing the vaccination, the IgG overall median titer was significantly elevated (21·7x103AU/mL). Both for uni- and multivariate logistic regression analyses women presented higher antibody levels than men, independent of age. Titers were significantly altered among age groups, decreasing by each increase in 10-year of age. At 3 months after completing the vaccination, anti-SARS-CoV-2 IgG titers were 6·3-fold diminished. This real-world post-vaccination data confirmed production of a frequent and elevated anti-SARS-CoV-2 IgG titers, associated with high protection rates. Females and younger participants had higher titer 15 days after vaccination, and despite the significant reduction from 15-to-90 days, those with higher pre-vaccination titers maintained higher levels throughout the remaining timepoints. INTERPRETATION: These findings support the need to track humoral immunity kinetics to uncover viral susceptibility and eventually implement re-vaccination, particularly in groups prone to lower humoral immune response. FUNDING: No external funding was received to conduct this study.

Clearance and persistence of SARS-CoV-2 RNA in patients with COVID-19.

Patients with coronavirus disease-2019 may be discharged based on clinical resolution of symptoms, and evidence for viral RNA clearance from the upper respiratory tract. Understanding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral clearance profile is crucial to establish a re-testing plan on discharge and ending isolation of patients. We aimed to evaluate the number of days that a patient needed to achieve undetectable levels of SARS-CoV-2 in upper respiratory tract specimens (nasopharyngeal swab and/or an oropharyngeal swab). The clearance and persistence of viral RNA was evaluated in two groups of positive patients: those who achieved two negative reverse transcription-polymerase chain reaction (RT-PCR) tests and those who kept testing positive. Patients were organized thereafter in two subgroups, mild illness patients discharged home and inpatients who had moderate to severe illness. Results from RT-PCR tests were then correlated with results from the evaluation of the immune response. The study evidenced that most patients tested positive for more than 2 weeks and that persistence of viral RNA is not necessarily associated with severe disease but may result from a weaker immune response instead.