Does the BNT162b2 COVID-19 vaccine affect sperm parameters of patients with a normal or an abnormal semen analysis?
Data were collected from male patients undergoing IVF treatment after completing ...vaccination between February 2021 and June 2021 (post-vaccine). For comparison, records of the same patients were reviewed before the vaccination (pre-vaccine) back to January 2017. Patients with azoospermia were excluded. Sperm parameters were compared between pre- and post-vaccine groups. Each patient served as self-control.
Seventy-two patients were included in the study (median interquartile range IQR age 35.7 33.0–43.0 years), of whom 57 had a normal semen analysis. The time between the first vaccine and the post-vaccine sperm analysis was 71.0 (40.5–104.8) days. The sperm parameters before and after the vaccination were as follows: sperm volume before 3.0 (2.0–4.0) and after 3.0 (1.6–3.9) ml, P = 0.02; sperm concentration before 26.5 (14.0–64.7) and after 31.0 (14.2–80.0) 106/ml, P = 0.35; and total motile sperm count before 33.7 (9.0–66.0) and after 29 (6.0–97.5)106, P = 0.96. Sub-group analyses were conducted for patients with male infertility and patients with a normal semen analysis. Neither of the sub-groups showed significant changes after vaccination.
Sperm parameters showed no significant changes after vaccination among men with a normal and abnormal semen analysis. Therefore, the BNT162b2 vaccine does not seem to affect sperm parameters. The preliminary results are reassuring for the entire global population, currently undergoing intense vaccination campaigns against COVID-19.
•Uveitis is a vision-threatening inflammation and can be elicited by vaccination.•We describe a case of uveitis that occurred after BNT162b2 COVID-19 vaccination.•After treatment with topical ...steroids, visual acuity was completely restored.
Uveitis is a vision-threatening inflammation and is considered an ophthalmic emergency. It generally arises as a result of autoimmune conditions, infections, or ocular trauma, but it may also occur as an isolated disorder. Over the past decades, several cases of vaccine-associated uveitis have been described, with the hepatitis B virus vaccine being the leading cause.
A case of anterior uveitis in a 23-year-old male, with onset 14 days after the second dose of BNT162b2 COVID-19 vaccine, is reported here. Initial symptoms were pain, photophobia, and red eye. Ocular examination showed pericheratic and conjunctival hyperaemia, posterior synechiae, and anterior chamber cells ± keratic precipitates in the lower quadrants. The posterior segment did not show any alteration, and optical coherence tomography ruled out the presence of cystoid macular oedema. After a 10-day treatment course of topical steroids and cycloplegic eye drops, the ocular inflammatory signs disappeared and visual acuity was completely restored. Even if causality remains presumed, a warning should be given to physicians about the possibility of eye inflammation following SARS-CoV-2 vaccination.
To examine the effectiveness of one dose of the COVID-19 vaccine on care-home residents.
Natural experiment.
We compared the effectiveness of single doses of Pfizer/BioNTech BNT162b2 (effective at 10 ...days) and AstraZeneca ChAdOx1 (effective at 14 days) vaccines in vaccinated and control (unvaccinated) homes. Using routine data, all care-homes reporting COVID-19 outbreaks between 11/12/2020 and 12/3/2021 in a sub-region of North West England were included.
Of 126 care-homes (4042 residents), with outbreaks, 55 (44%, 1686 residents) reported onset dates before vaccination commenced; 38 (30%, 1304 residents) reported onset < 10 (BNT162b2) and < 14 days (ChAdOx1) after vaccine administration; and 33 (26%, 1052 residents) reported onset > 10 (BNT162b2) and > 14 (ChAdOx1) days after vaccination. Eighty-nine (71%) homes used ChAdOx1 vaccine. A single dose of vaccine before the outbreak onset significantly lowered the risk of symptoms (reduced by 48%), positivity (by 65%), hospitalisation (by 68%), and death (by 81%). Some vaccine effectiveness was also noted in care-homes that received one dose of vaccine within 10–14 days of outbreak onset. The number needed to vaccinate to prevent one resident from COVID-19-related hospitalisation was 34, and death was 17.
This real-world, natural experiment adds to the evidence of COVID-19 vaccine effectiveness from different studies using varying designs. In the context of lockdown's impact on infection rates and on-going care-home outbreaks, a single dose of either ChAdOx1 or BNT162b2 vaccine had a significant impact on reducing COVID-19 related hospitalisation and death in care-home residents. Natural experiments should be used more in public health.
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Two doses of the BNT162b2 mRNA vaccine are highly effective against SARS-CoV-2. Here, we tested the antibody neutralization against Omicron SARS-CoV-2 after 2 and 3 doses of BNT162b2. Serum from ...vaccinated individuals was serially tested for its ability to neutralize wild-type SARS-CoV-2 (USA-WA1/2020) and an engineered USA-WA1/2020 bearing the Omicron spike glycoprotein. At 2 or 4 weeks post dose 2, the neutralization geometric mean titers (GMTs) against the wild-type and Omicron-spike viruses were 511 and 20, respectively; at 1 month post dose 3, the neutralization GMTs increased to 1,342 and 336; and at 4 months post dose 3, the neutralization GMTs decreased to 820 and 171. The data support a 3-dose vaccination strategy and provide a glimpse into the durability of the neutralization response against Omicron.
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•Two doses of BNT162b2 are not sufficient to elicit robust neutralization against Omicron•Three doses of BNT162b2 confer substantial neutralization against Omicron•Neutralization against Omicron remains robust at 4 months after dose 3 of BNT162b2
Through serially testing BNT162b2-vaccinated human sera against SARS-CoV-2 and its Omicron variant, Xia et al. found that 2 doses of BNT162b2 are insufficient to elicit robust neutralization against Omicron. Three doses increase the magnitude and breadth of neutralization against Omicron and remains robust for up to 4 months post dose 3.
Data on the safety and efficacy of SARS-CoV-2 vaccines in immunocompromised populations are sparse.
We conducted a prospective study of 77 heart transplant (HT) recipients vaccinated with two doses ...of BNT162b2 vaccine and monitored for adverse events following both doses, the receptor-binding domain (RBD) IgG response, and neutralizing antibodies.
BNT162b2 vaccination was associated with a low rate of adverse events, characterized mostly by pain at the injection site. By a mean 41 days post second dose there were no clinical episodes of rejection, as suggested by a troponin leak or allograft dysfunction. At a mean 21 days following the second dose, IgG anti-RBD antibodies were detectable in 14 (18%) HT recipients. Immune sera neutralized SARS-CoV-2 pseudo-virus in 8 (57%) of those with IgG anti-RBD antibodies. Immunosuppressive regimen containing mycophenolic acid was associated with lower odds of an antibody response (OR = 0.12, p = 0.042).
Whether a longer time-frame for observation of an antibody response is required after vaccination in immunosuppressed individuals remains unknown.
Preliminary evidence suggests patients on hemodialysis have a blunted early serological response to SARS-CoV-2 vaccination. Optimizing the vaccination strategy in this population requires a thorough ...understanding of predictors and dynamics of humoral and cellular immune responses to different SARS-CoV-2 vaccines.
This prospective multicenter study of 543 patients on hemodialysis and 75 healthy volunteers evaluated the immune responses at 4 or 5 weeks and 8 or 9 weeks after administration of the BNT162b2 or mRNA-1273 vaccine, respectively. We assessed anti-SARS-CoV-2 spike antibodies and T cell responses by IFN-γ secretion of peripheral blood lymphocytes upon SARS-CoV-2 glycoprotein stimulation (QuantiFERON assay) and evaluated potential predictors of the responses.
Compared with healthy volunteers, patients on hemodialysis had an incomplete, delayed humoral immune response and a blunted cellular immune response. Geometric mean antibody titers at both time points were significantly greater in patients vaccinated with mRNA-1273 versus BNT162b2, and a larger proportion of them achieved the threshold of 4160 AU/ml, corresponding with high neutralizing antibody titers in vitro (53.6% versus 31.8% at 8 or 9 weeks, P <0.0001). Patients vaccinated with mRNA-1273 versus BNT162b2 exhibited significantly greater median QuantiFERON responses at both time points, and a larger proportion achieved the threshold of 0.15 IU/ml (64.4% versus 46.9% at 8 or 9 weeks, P <0.0001). Multivariate analysis identified COVID-19 experience, vaccine type, use of immunosuppressive drugs, serum albumin, lymphocyte count, hepatitis B vaccine nonresponder status, and dialysis vintage as independent predictors of the humoral and cellular responses.
The mRNA-1273 vaccine's greater immunogenicity may be related to its higher mRNA dose. This suggests a high-dose vaccine might improve the impaired immune response to SARS-CoV-2 vaccination in patients on hemodialysis.
The repeated waves of the COVID-19 pandemic have highlighted the necessity to optimize vaccine responses in immunocompromised populations. We investigated the safety and immunogenicity of a third, ...booster, dose of the Pfizer BNT162b2 vaccine in heart transplant (HT) patients.
The cohort comprised 96 adult HT patients who received a third homologous dose of the BNT162b2 vaccine 168 days after the second dose. The vaccine-induced antibody responses of both receptor-binding domain (RBD) IgG and neutralizing antibodies were assessed in all patients, with a positive antibody response being defined as the presence of either IgG anti-RBD or neutralizing antibodies. For a subset of patients, T cell response was also studied.
The third dose was associated with a low rate of adverse events, mostly mild pain at the injection site. No serious adverse events were recorded, and there were no episodes of rejection. At 18 days following the third dose of the vaccine, the positive antibody response increased from 23% to 67%, with a corresponding increase in neutralizing capacity. The third dose elicited SARS-CoV-2 neutralization titers >9-fold and IgG anti-RBD antibodies >3-fold of the range achieved after the two primary doses. Mycophenolate use, lower eGFR and higher C-reactive protein were independently associated with a reduced likelihood of generating an immune response. Importantly, a specific T-cell response following the third dose was evident in the majority of transplant recipients.
An homologous third booster dose of the BNT162b2 vaccine gave overall consistent tolerability and a good safety profile, while eliciting humoral and cellular immune responses.
Abstract
Objective
The effectiveness of COVID-19 vaccinations wanes due to immune evasion by the B.1.1.529 (Omicron) variant and diminished antibody titres over time. We aimed to evaluate the benefit ...of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARDs).
Methods
This retrospective analysis included ARD patients aged 18 years or older and members of Clalit Health Services in Israel (which at the time of the study insured 52% of the entire population), and covered the period from 16 January 2022 to 31 March 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who had received three doses of the BNT162b2 vaccine (the control group) with those who had received the fourth dose. The primary outcome was COVID-19 infection, which was analysed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19–related hospitalizations and COVID-19–related death.
Results
We included 43 748 ARD patients, of whom 27 766 and 15 982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6942 (25.0%) of the control group and 1754 (11.0%) of the fourth dose group (P < 0.001). Patients vaccinated with the fourth dose had a lower risk of COVID-19 infection than the entire cohort Hazard Ratio (HR) 0.54, 95% CI 0.52, 0.58 and throughout every subgroup regardless of the baseline characteristic or medical treatment, except for rituximab. A similar association was observed for risk of COVID-19–related hospitalization (HR 0.36, 95% CI 0.22, 0.61) and of COVID-19–related death (HR 0.41, 95% CI 0.24, 0.71).
Conclusion
A fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared with three doses among patients with no history of COVID-19 infection.
Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters?
A prospective cohort study was conducted at a single large tertiary centre in Israel ...between February and March of 2021. Semen samples from 75 fertile men were analysed 1–2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology.
The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 × 106/ml, with only a single participant (1.3%) with a sperm count of 12.5 × 106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO.
The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.
In addition to serum immunoglobulins, memory B cell (MBC) generation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is another layer of immune protection, but the quality of MBC ...responses in naive and coronavirus disease 2019 (COVID-19)-recovered individuals after vaccination remains ill defined. We studied longitudinal cohorts of naive and disease-recovered individuals for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of antibody repertoires, affinity, and neutralization against variants of concern (VOCs) using unbiased cultures of 2,452 MBCs. Upon boosting, the MBC pool of recovered individuals expanded selectively, matured further, and harbored potent neutralizers against VOCs. Although naive individuals had weaker neutralizing serum responses, half of their RBD-specific MBCs displayed high affinity toward multiple VOCs, including delta (B.1.617.2), and one-third retained neutralizing potency against beta (B.1.351). Our data suggest that an additional challenge in naive vaccinees could recall such affinity-matured MBCs and allow them to respond efficiently to VOCs.
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•Vaccination boosts high-affinity RBD memory B cells (MBCs) in COVID-19-recovered patients•Boosted MBCs retain their diversity and express potent variant-neutralizing antibodies•SARS-CoV-2-naive individuals show low serum neutralization of variants after vaccination•Maturation of MBCs in naive individuals allows them to respond to variants of concern
To better understand B cell responses to SARS-CoV-2 mRNA vaccination, Sokal et al. analyzed memory B cells from COVID-19-recovered and naive individuals. In recovered individuals, vaccination amplifies a broad repertoire of matured MBCs and generates variant-neutralizing plasma cells. In naive individuals, vaccination induces an MBC pool containing potent neutralizing clones against all current variants of concern, including beta and delta.
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