Effect of Vitamin D3 supplementation vs. dietary-hygienic measures on SARS-COV-2 infection rates in hospital workers with 25-hydroxyvitamin D3 levels >20 ng/mL (preprint)

Background. There is scant information on the effect of supplementation with vitamin D3 in SARS-COV-2 infection cases when patient 25-hydroxyvitamin D3 [25(OH)D3] levels are between 20-100ng/mL. Our aim was to evaluate the effect of supplementation with vitamin D3 vs. dietary-hygienic measures on the SARS-COV-2 infection rate in participants with serum 25(OH)D3 levels >20ng/mL. Methods. We invited hospital workers with 25(OH)D3 levels between 20-100 ng/mL and no previous SARS-COV-2 infection; they were randomized as follows: treatment options were a) vitamin D3 supplementation (52,000 IU monthly, G1) or b) dietary-hygienic measures (G2). We conducted a 3- to 6-month follow-up of SARS-COV-2 infections. Participants with 25(OH)D3 levels <20 ng/mL were also analyzed. We divided these latter participants depending on whether they were supplemented (G3) or not (G4). Results. We analyzed 198 participants, with an average age of 44.4 (SD 9) years, and 130 (65.7%) were women. G1 had less cases of SARS-COV-2 infection than G2 after a follow-up of 3- to 6-months (p<0.05). There were no differences between G3 and G4 at the 3- and 6-month follow-up cutoff points (p>0.05). Using mixed effect Cox regression analysis in 164 participants that completed six months of follow-up, vitamin D3 supplementation appeared to act as a protective factor against SARS-COV-2 infection (HR 0.21, p=0.008) in G1 and G2. None of the participants treated with the supplementation doses had serum 25(OH)D3 levels > 100ng/mL. Conclusion. Vitamin D3 supplementation in participants with 25(OH)D3 levels between 20-100 ng/mL have a lower rate of SARS-COV-2 infection in comparison with the use of dietary-hygienic measures at six months follow-up.

Analysis of immunization, adverse events, and efficacy of a fourth dose of BNT162b2 vaccine (preprint)

Importance: Scarce information exists concerning the seroconversion and adverse events after immunization (AEFI) of the fourth dose of a SARS-COV-2 vaccine. Objective: Correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI of the fourth dose of BNT162b2 mRNA. Design: Observational study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured 21-28 days after the exposition of the first, and second dose, three months after the second dose, 1-7 days after the third dose, before the fourth dose, and 21-28 days after the fourth dose of BNT162b2 mRNA. Setting: The study was conducted on healthcare workers of a private hospital in Northern Mexico. Participants: Inclusion criteria were healthcare workers of both genders, any age, who planned to conclude the immunization regimen. The exclusion criteria were previously given any SARS-CoV-2 vaccine prior to study entry. Intervention: Subjects were exposed to four doses of the BNT162b2 mRNA vaccine. Main Outcome and Measures: The anti-S1 and anti-S2 IgG antibodies against SARS-CoV-2 in plasma samples were measured with chemiluminescence immunoassay developed by DiaSorin. Results: We recruited 112 subjects [43 (SD 9) years old, 74% women]. After the first dose, subjects had a median (IQR) AU/ml IgG of 122(1904), with an increase to 1875 (2095) after the second dose, 3020 (2330) after the third dose, and 4230 (3393) after 21-28 of a fourth dose (p<0.01). The number (%) of any AEFI between doses was 90 (80.4), 89(79), 65(58), 69 (61.5), after first, second, third, and fourth, respectively, p<0.001. After the fourth dose, the most frequent AEFI was pain at the injection site (87%). Fever was slightly more frequent after the third and fourth doses, 9 (13.8) and 8 (11.4%) cases, respectively, and adenopathy was more frequent after the fourth dose [in11(15.7%) cases]. There was a correlation between AEFI in the fourth dose with gender and antibody levels (p<0.05). The highest proportion of AEFI was considered mild after the fourth dose. During the Omicron outbreak, 6 (5.3%) had mild SARS-CoV-2 during 8-28 days of the fourth dose. Conclusions and Relevance: The fourth dose of BNT162b2mRNA increases S1/S2 IgG 33.6 times with mild adverse events.

Analysis of immunization time, amplitude, and adverse events of seven different vaccines against SARS-CoV-2 across four different countries. (preprint)

Background: Scarce information exists in relation to the comparison of seroconversion and adverse events following immunization (AEFI) with different SARS-CoV-2 vaccines. Our aim was to correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI. Methods: A multicentric comparative study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured at baseline, 21-28 days after the first and second dose (when applicable) of the following vaccines: BNT162b2 mRNA, mRNA-1273, Gam-COVID-Vac, Coronavac, ChAdOx1-S, Ad5-nCoV and Ad26.COV2. Mixed model and Poisson generalized linear models were performed. Results: We recruited 1867 subjects [52 (SD 16.8) years old, 52% men]. All vaccines enhanced anti-S1 and anti-S2 IgG antibodies over time (p<0.01). The highest increase after the first and second dose was observed in mRNA-1273 (p<0.001). There was an effect of previous SARS-CoV-2 infection; and an interaction of age with SARS-CoV-2, Gam-COVID-Vac and ChAdOx1-S (p<0.01). There was a negative correlation of Severe or Systemic AEFI (AEs) of naive SARS-CoV-2 subjects with age and sex (p<0.001); a positive interaction between the delta of antibodies with Gam-COVID-Vac (p=0.002). Coronavac, Gam-COVID-Vac and ChAdOx1-S had less AEs compared to BNT162b (p<0.01). mRNA-1273 had a higher number of AEFIs. The delta of the antibodies showed an association with AEFIs in previously infected individuals (p<0.001). Conclusions: The magnitude of seroconversion is predicted by age, vaccine type and SARS-CoV-2 exposure. AEs are correlated with age, sex, and vaccine type. The delta of the antibody response is positively correlated with AEs in patients previously exposed to SARS-CoV-2.

Effect of the third dose of BNT162b2 vaccine in quantitative SARS-CoV-2 spike 1-2 IgG antibody titers in healthcare workers (preprint)

Background: Vaccination is our main strategy to control SARS-CoV-2 infection. Given a decrease in the quantitative SARS-CoV-2 spike 1-2 IgG antibody titers three months following the second BNT162b2 dose, healthcare workers got a third booster dose after six months of completing the original scheme. This study aimed to analyze quantitative SARS-CoV-2 spike 1-2 IgG antibody titers and safety of the third dose. Material and methods: A prospective longitudinal cohort study included healthcare workers who received a third booster dose after six months of the complete BNT162b2 regimen. We assessed the quantitative SARS-CoV-2 spike 1-2 IgG antibody titers 21-28 days after the first and second dose, three months after the complete scheme, 1-7 days following the third dose, and 21-28 days after the boost. Results: The cohort comprised 168 non-immunocompromised participants of 41(10) years old, 67% being women. The third dose was associated with increasing the quantitative antibody titers, regardless of previous SARS-CoV-2 history. In negative SARS-CoV-2 history, the median (IQR) antibody titers increased from 379 (645.4) to 2960 (2010), while in positive SARS-CoV-2 history, from 590 (1262) to 3090 (2080). The third dose had less number of total side effects compared to the other two shots. The most common side effect after the third BNT162b2 shot was pain at the injection site (n=82, 84.5%), followed by tiredness (n=45, 46.4%), with a mild severity (n=36, 37.1%). Tiredness, myalgias, arthralgias, fever, and adenopathy were proportionally higher following the third dose than the two-dose regimen (p<0.05). Conclusion: The third dose applied after six months of the original BNT162b2 regimen provided a good humoral immune response by elevating the quantitative SARS-CoV-2 spike 1-2 IgG antibody titers. The booster dose was well tolerated with no severe side effects after the additional BNT162b2 dose.

Effect of heterologous vaccination regimen with Ad5-nCoV CanSinoBio and BNT162b2 Pfizer in SARS-CoV-2 IgG antibodies titers. (preprint)

Introduction: The efficacy with one dose Ad5-nCoV has been concerned. As a result, some patients have self-reported getting a boost with BNT. Therefore, this study aimed to compare SARS-CoV-2 spike 1-2 IgG antibodies in plasma samples between two groups: one group immunized with Ad5-nCoV and another with a heterologous vaccination regimen with Ad5-nCoV and BNT. Methods: Prospective observational study included a subgroup analysis of patients who received the Ad5-nCoV immunization during the first trimester of 2021 in a Northern city of Mexico; and agreed to a follow-up for an entire year through SARS-CoV-2 specific IgG antibodies measurement samples. During the three months follow-up, some patients self-reported receiving a BNT boost. We report IgG levels from basal, 21-28 days after Ad5-nCoV dose, three months, and an additional 21-28 days after BNT boost. Results: Seventeen patients 40 (16) years old, 52.9% men, were analyzed. We created four groups: (G1) patients vaccinated with Ad5-nCoV with no history of SARS-COV-2 (n=4), (G2) patients vaccinated with Ad5-nCoV and the first shot of BNT with no history of SARS-COV-2 (n=6), (G3) patients vaccinated with Ad5-nCoV with history of SARS-COV-2 (n=5), and (G4) patients vaccinated with Ad5-nCoV and the first shot of BNT with history of SARS-COV-2 (n=2). The group immunized with a heterologous vaccine scheme reported higher antibodies after 21-28 days of follow-up after BNT boost. Median (IQR): G1 46.7 (-), G2 1077.5 (1901), G3 1158.5 (2673.5), and G4 2090 (-) (p<0.05). Headache was the most frequent adverse reaction when patients received Ad5-nCoV (n = 10, 83%), and pain at the injection site was the most frequent adverse reaction with BNT boost (n = 5, 83.3%). Conclusion: Patients receiving a BNT boost after Ad5-nCoV had higher SARS-CoV-2 spike 1-2 IgG antibodies titers with no severe adverse reaction.