Anti-PF4 positivity and platelet activation after Ad26.COV2·S vaccination in Brazil.

INTRODUCTION: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil. METHODS: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays. RESULTS: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination. CONCLUSIONS: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.

An observational study of adverse drug reactions to COVID-19 vaccines reported to the New Mexico poison center hotline.

INTRODUCTION: Post-marketing data on coronavirus vaccines are limited. This study evaluated adverse reactions reported to a statewide hotline after the administration of a coronavirus disease-2019 (COVID-19) vaccine. METHODS: We collected reports between 1 December 2020 through 30 August 2021 of any individual 12 years of age and older who received an FDA EUA-approved vaccine and experienced an adverse reaction. For each case, we collected vaccine brand, demographics, adverse reaction type, severity, onset of reaction, duration, and outcome. Relative risk analyses were conducted to investigate factors associated with vaccine adverse reactions. RESULTS: 638 adverse drug reaction cases were recorded. The majority identified as female (70.8%) and the median age was 56. Implicated brands were Pfizer BNT162b2 (46.6%), Moderna mRNA-1273 (43.41%), and Janssen Ad26.COV2.S (8.78%). Although the lowest number of cases was with Janssen, this vaccine had the highest incident rate based on reactions per 100,000 doses. Adverse reactions with the highest incidence were systemic reactions (92.7%), injection-site reactions (8.5%), and local non-injection-site reactions (10.4%), with most judged as minor severity. Relative risk was higher for Moderna compared to Pfizer for injection-site non-severe (RR 2.01) and injection-site severe (RR 1.94) reactions. Janssen had a higher risk of headache, dyspnea, and vision changes compared to Pfizer, and a higher risk of headache compared to Moderna. The relative risk for fever, chills, and lymphadenopathy was higher for the second dose than the first dose for all patients. CONCLUSION: This observational study analyzing adverse drug reactions of the COVID-19 vaccine found that most complaints concerned systemic reactions. We found reaction differences among vaccine brands, between first and second doses for some effects, and selected recurrent events. Poison control centers are uniquely positioned to conduct post-marketing surveillance for the new vaccines as they are available 24/7 to the public and are healthcare providers. Further post-marketing studies are essential to provide a holistic safety profile of COVID-19 vaccines.

Neutralizing Antibody Responses Elicited by Inactivated Whole Virus and Genetic Vaccines against Dominant SARS-CoV-2 Variants during the Four Epidemic Peaks of COVID-19 in Colombia.

Several SARS-CoV-2 variants of concern (VOC) and interest (VOI) co-circulate in Colombia, and determining the neutralizing antibody (nAb) responses is useful to improve the efficacy of COVID-19 vaccination programs. Thus, nAb responses against SARS-CoV-2 isolates from the lineages B.1.111, P.1 (Gamma), B.1.621 (Mu), AY.25.1 (Delta), and BA.1 (Omicron), were evaluated in serum samples from immunologically naïve individuals between 9 and 13 weeks after receiving complete regimens of CoronaVac, BNT162b2, ChAdOx1, or Ad26.COV2.S, using microneutralization assays. An overall reduction of the nAb responses against Mu, Delta, and Omicron, relative to B.1.111 and Gamma was observed in sera from vaccinated individuals with BNT162b2, ChAdOx1, and Ad26.COV2.S. The seropositivity rate elicited by all the vaccines against B.1.111 and Gamma was 100%, while for Mu, Delta, and Omicron ranged between 32 to 87%, 65 to 96%, and 41 to 96%, respectively, depending on the vaccine tested. The significant reductions in the nAb responses against the last three dominant SARS-CoV-2 lineages in Colombia indicate that booster doses should be administered following complete vaccination schemes to increase the nAb titers against emerging SARS-CoV-2 lineages.