Vaccine side-effect or coincidence?
Thromboembolism and the Oxford–AstraZeneca COVID-19 vaccine: side-effect or coincidence?
According to the European Medicines Agency, 30 cases of thromboembolic events (predominantly venous) had been reported by March 10, 2021, among the approximately 5 million recipients of the Oxford–AstraZeneca COVID-19 vaccine. We first used the Danish Civil Registration System to identify all Danes who were at least 18 years old between Jan 1, 2010, and Nov 30, 2018. Using data from the Danish National Patient Registry, we then identified all first-time cases of venous thromboembolism in the general adult population in this period. The study population aged 18–99 years included 4 915 426 individuals, with a total follow-up time of 38 449 703 person-years. The incidence rate per 1000 person-years was 1·76 (95% CI 1·75–1·78) for venous thromboembolism. In a population of 5 million people, this incidence would correspond to approximately 169 expected cases of venous thromboembolism per week, or 736 expected cases per month. Here, based on pre-pandemic incidence rates from the entire Danish population, we report that the number of venous thromboembolisms reported in relation to the Oxford–AstraZeneca COVID-19 vaccine does not seem to be increased beyond the expected incidence rate.
Serum sample neutralisation of BBIBP-CorV and ZF2001 vaccines to SARS-CoV-2 501Y.V2 [Chinese vaccines neutralisation of South African variant]
We assessed neutralisation activity in 24 serum samples from participants in two clinical trials, 12 who had been vaccinated with BBIBP-CorV and 12 who had been vaccinated with ZF2001. All 24 serum samples from either recipients of BBIBP-CorV or ZF2001 largely preserved neutralisation of the 501Y.V2 [B.1.351—South African] variant, with slightly reduced geometric mean titres (GMTs) compared with their titres against the wild type or D614G strains (appendix p 2). For BBIBP-CorV, the GMT decreased from 110·9 (95% CI 76·7–160·2) to 71·5 (51·1–100·1). For ZF2001, this the GMT decreased from 106·1 (95% CI 75·0–150·1) to 66·6 (51·0–86·9). Our findings suggest that the 501Y.V2 [South African] variant does not escape the immunity induced by vaccines targeting the whole virus (BBIBP-CorV) or S protein dimeric RBD (ZF2001).
Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies
We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.
Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48 440 adult patients
We identified 48 440 adult patients with a COVID-19 diagnosis from 1 January 2020 to 21 October 2020, with at least three exercise vital sign measurements from 19 March 2018 to 18 March 2020. Patients with COVID-19 who were consistently inactive had a greater risk of hospitalisation (OR 2.26; 95% CI 1.81 to 2.83), admission to the ICU (OR 1.73; 95% CI 1.18 to 2.55) and death (OR 2.49; 95% CI 1.33 to 4.67) due to COVID-19 than patients who were consistently meeting physical activity guidelines. Consistently meeting physical activity guidelines was strongly associated with a reduced risk for severe COVID-19 outcomes among infected adults. We recommend efforts to promote physical activity.
Antibody evasion by the P.1 strain of SARS-CoV-2
New strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization.