Incidence of anti-platelet factor4/polyanionic antibodies, thrombocytopenia, and thrombosis after COVID-19 vaccination with ChAdOx1 nCoV-19 in Thais (preprint)

Background The prevalence of anti-platelet factor 4 (PF4)/polyanionic antibodies occurring after vaccination with ChAdOx1 nCoV-19 is low. Most of these antibodies are not associated with vaccine-induced thrombotic thrombocytopenia. It remains unknown whether these antibodies are preexisting or occur as a result of vaccination. In this study, we demonstrated the incidence of anti-PF4/polyanionic antibodies, thrombocytopenia, and thrombosis after vaccination with ChAdOx1 nCoV-19 in a large cohort of Thais.Methods We conducted a prospective study in a cohort of health care workers and members of the general population who received COVID-19 vaccination with ChAdOx1 nCoV-19. Blood collection for complete blood count, D-dimer, and anti-PF4/polyanionic antibodies was performed before vaccination (day 0), day 10, and day 28 after vaccination. Anti-PF4/polyanionic antibodies were detected using enzyme-link immunosorbent assay (ELISA). Functional assay was performed for all positive ELISA tests.Results A total of 720 participants were included in the study. 214 participants received both the first and second doses, 91 participants received only the first, 51 received only the second, and 364 received the third booster dose of ChAdOx1 nCoV-19. Median age was 42 years (IQR, 34–53). 67% of participants were female. Three participants developed seroconversion, yielding an incidence of vaccination-induced anti-PF4/polyanionic antibodies of 0.42% (95% confidence interval 0.08, 1.23). Fourteen (1.9%) participants had preexisting anti-PF4/polyanionic antibodies before the vaccination but their optical density of anti-PF4/polyanionic antibodies did not significantly increase over time. None of the anti-PF4/polyanionic positive sera induced platelet aggregation. Abnormal D-dimer levels following vaccination were not different among the positive and negative anti-PF4/polyanionic groups (11.8% vs 13.2%, p = 0.86). Thrombocytopenia occurred in one person with negative anti-PF4/polyanionic antibodies. No clinical thrombosis or bleeding occurred.Conclusion We found a low incidence of seroconversion of anti-PF4/polyanionic antibodies after vaccination with ChAdOx1 nCoV-19 in Thais. Most of the anti-PF4/polyanionic antibodies were preexisting and did not significantly increase after vaccination with ChAdOx1 nCoV-19. Following vaccination, some participants with anti-PF4/polyanionic antibodies had elevated D-dimer levels, while only one developed thrombocytopenia and no thrombotic events were observed.

Good recovery of immunization stress-related responses presenting as cluster of stroke-like events following CoronaVac and ChAdOx1 vaccinations (preprint)

Background Immunization stress-related responses presenting as stroke-like symptoms may develop following COVID-19 vaccination. This study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination. Methods We conducted a retrospective study of the secondary data of reported adverse events following COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score (i.e., defining the degree of severity/dependence, with higher scores indicating greater disability). The affected side was evaluated for associations with the injection site. Results In total, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28–42) years in patients receiving CoronaVac and 46 (33.5–60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16–960) min and 30 (8.8–750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (53.8%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 90% of those receiving ChAdOx1 recovered well (modified Rankin scores ≤2, indicating slight or no disability). Conclusions Immunization stress-related responses presenting as stroke-like symptoms can develop following COVID-19 vaccination. Symptoms that are more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.

Prevalence of anti-platelet factor4/polyanionic antibodies after COVID-19 vaccination with ChAdOx1 nCoV-19 and CoronaVac in Thais (preprint)

Introduction: Vaccine-induced thrombotic thrombocytopenia (VITT) has been reported after vaccination with the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 in European countries. To date, no case of VITT has been reported in Thais after COVID-19 vaccination. We determined the frequency of anti-PF4/polyanionic antibodies in the Thai population receiving the COVID-19 vaccines. Methods: We conducted a cross-sectional study to evaluate the prevalence of anti-PF4/polyanionic antibodies in health care workers who received COVID-19 vaccination with ChAdOx1 nCoV-19 or CoronaVac within 7-35 days. A control population who had not been vaccinated was also included. Anti-PF4/polyanionic antibodies were detected using enzyme-link immunosorbent assay (ELISA). Functional assay with platelet aggregation was performed for all positive anti-PF4/polyanionic antibody ELISA tests. Results: A total of 646 participants were included in the study. 221 received ChAdOx1 nCoV-19, 232 received CoronaVac, and 193 participants were in the control group. The prevalence of anti-PF4 antibodies was 2.3% (95% confidence interval [CI] 0.7 to 5.2), 1.7% (95% CI, 0.5 to 4.4) in the ChAdOx1 nCoV-19 and CoronaVac groups, respectively. There was no positive test in the control group. None of the PF4/polyanionic positive sera induced platelet aggregation. Conclusion: We found a low prevalence of anti-PF4 antibodies in Thais after vaccination with ChAdOx1 nCoV-19 and CoronaVac. Low titer positive PF4/polyanionic ELISA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19.

Incidence of thromboembolism in patients with COVID-19: a systematic review and meta-analysis (preprint)

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the incidence of thromboembolism has been increasingly reported. The aim of this systematic review was to explore the incidence of venous and arterial thromboembolism among COVID-19 patients requiring hospitalization. Methods: Medline, Embase, Scopus, and grey literature were searched until May 2020. Observational studies reported on the incidence of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) or arterial thromboembolism (ATE) were included. The pool incidences and their 95% confidence intervals (CI) were calculated using the random-effects model. Results: A total of 36 studies were included. In the intensive care unit (ICU) setting, the pooled incidence of VTE was 28% (95% CI, 22-34%). Subgroups based on compression ultrasound (CUS) screening revealed a higher incidence of DVT in the CUS screening group than in the no CUS screening group (32% [95% CI, 18-45%] vs. 6% [95% CI, 4-9%]). The pooled incidence of ATE in ICU was 3% (95% CI, 2-5%). In the non-ICU setting, the pooled incidence of VTE was 10% (95% CI, 6-14%,). Conclusions: The incidence of VTE in COVID-19 patients was higher in the ICU setting than in the non-ICU setting, and also significantly higher in studies that incorporated the CUS screening protocol. The incidence of ATE in the ICU setting was low. VTE prophylactic measures should be given to all hospitalized patients diagnosed with COVID-19.