Clotting, bleeding issues uncommon with AstraZeneca COVID-19 vaccine

The AstraZeneca-Oxford COVID-19 vaccine is associated with some increases in bleeding and clotting events, according to a BMJ study yesterday, but experts say the benefits outweigh the risks.

The researchers compared 28-day post-vaccination comorbidities in 291,264 Danish and Norwegian adults under 65 with the general population. Most (79.0%) were women, with a median age for all patients of 44 to 45. People who had experienced any adverse events in the past year were excluded.

The results show no association between arterial events and COVID vaccination, but the risk of venous thromboembolism was increased 1.97-fold, though to only 11 excess occurrences per 100,000 vaccinations. Cerebral venous thromboembolisms in particular increased 20.25-fold, resulting in 2.5 excess occurrences per 100,000 vaccinations. A BMJ editorial by Rafael Perera, DPhil, and John Fletcher, MB BChir, MPH, however, notes that COVID itself is associated with 4.3 excess brain blood clots per 100,000 infections.

Standardized morbidity ratios were slightly higher for thrombocytopenia or clotting disorders (1.52) as well as any bleeding (1.23). The researchers say increased surveillance could also be a factor.

Stratifying the data by age affected only venous thromboembolism occurrence (2.99 morbidity ratio in those younger than 45 vs 1.58). While vaccinated men had a 0.67 morbidity ratio for venous thromboembolism, overall the researchers say the data are not conclusive and that more studies are needed to understand populations that may have increased risks.

A BMJ blog post by Paul R. Hunter, MB ChB, MD, MBA, points out that some adverse events may have gone undetected due to the simplification of ICD-10 codes, which were used for data analysis, or because patients did not seek hospital care. Still, he, the researchers, and the editorial authors agree that the benefits of the AstraZeneca vaccine's outweigh the risks.

"Comparing vaccine adverse event rates to background population rates is appropriate for rare diseases, since most people are never exposed to the disease but are exposed to risk of adverse events if vaccinated. The situation is different in a pandemic," Perera and Fletcher write. "The choice we nearly all face is between eventual SARS-CoV-2 infection or vaccination. The Oxford-AstraZeneca vaccine is clearly a good choice, despite the likely risks found by Pottegård and colleagues."
May 5 BMJ study, editorial, and blog post

Lung abnormalities can persist a year post-COVID

Almost one in three patients' lungs exhibited a lower ability to diffuse gas into the bloodstream 1 year after hospital discharge following severe COVID-19, according to a study yesterday in The Lancet Respiratory Medicine.

The researchers looked at 83 healthy adults who were diagnosed as having severe COVID-19 pneumonia at a Wuhan University hospital in China. After enrollment in February and March 2020, the patients were followed up 3, 6, 9, and 12 months post-discharge. The study excluded patients who received intubation and mechanical ventilation in the hospital or who had a history of smoking or comorbidities.

In pulmonary function tests, the median diffusing capacity of the lungs for carbon monoxide (DLCO) was 77% of the predicted value at 3 months, 76% at 6 months, and 88% at 12 months; median forced vital capacity (FVC) was 92%, 92%, and 98% of predicted value, respectively. By 12 months, 27 (32.5%) still had impaired DLCO, and 9 (10.8%) had reduced FVC, a measure of breathing ability. Despite this, patients exhibited improved exercise and breathlessness symptoms.

Almost 80% of patients (65) showed residual computed tomography (CT) abnormalities 3 months after discharge, and after a year, 24.1% (20) did. High-resolution CT (HRCT) showed no evidence of established fibrosis or progressive interstitial changes. Overall, the researchers found significant differences in pulmonary function test parameters between patients with normal versus abnormal HRCT scores a year after discharge.

Female sex was associated with impaired DLCO (odds ratio [OR], 8.61; 95% confidence interval [CI], 2.83 to 26.2). Data also associated peak HRCT pneumonia scores with radiologic abnormalities (OR, 1.36; 95% CI, 1.13 to 1.62).

Piero L. Olliaro, MD, PhD, writes in a commentary, "The findings on lung function and how these are reflected in functional tests therefore apply to a selected population at the beginning of the pandemic and both presenting characteristics and case management have evolved since." Thus, he calls for more research to understand the long-term impact of COVID-19 on the lungs.
May 5 Lancet Resp Med study and commentary