ABSTRACT
Background: The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time in this patient population. Method(s): We utilized the N3C data set with uncensored dates of service to identify all chronic liver disease (CLD) patients with and without cirrhosis who had SARS-CoV-2 infection as of 9/10/2022. We described the observed 30-day case fatality rate by month of infection. We used adjusted Cox survival analyses to calculate relative hazard of death by month of infection compared to infection in March 2020 at the onset of the COVID-19 pandemic. Result(s): We identified 110,477 total CLD patients infected with SARS-CoV-2 between 3/2020-7/2022: 25,067 (23%) with cirrhosis and 85,410 (77%) without cirrhosis. Of the 110,477 total CLD patients, 39,595 (36%) were vaccinated and 70,882 (64%) unvaccinated. The overall observed 30-day case fatality rate during the entire study period was 1.4% (1,198) for CLD patients without cirrhosis and 7.7% (1,930) for those with cirrhosis. The observed 30-day case fatality rate by month of infection is displayed in Fig. 1. Compared to infection in March 2020, the adjusted hazard of death at 30 days for infection in July 2022 was HR 0.083 (95% CI 0.026-0.27) for CLD patients without cirrhosis and HR 0.32 (95% CI 0.17-0.61) for those with cirrhosis. Conclusion(s): In this N3C study, we found that the observed 30-day case fatality rate decreased progressively for both CLD patients with and without cirrhosis. Yet, the decrease in all-cause mortality was four times greater for patients without cirrhosis compared to those with cirrhosis. Despite improvements in SARS-CoV-2 treatments, patients with cirrhosis remain at risk of adverse outcomes. (Figure Presented).
ABSTRACT
In the last two years, billions of individuals worldwide have been safely vaccinated against SARS-CoV-2, the virus that causes COVID-19. However, a substantial number of people experience mild to moderate side effects, which may hamper vaccine and booster uptake;understanding the processes underlying differential responses to these vaccines can help to improve global vaccination efforts. Variation in HLA has been linked to disease outcome in COVID-19, and HLA-A*03:01 has previously been reported to increase risk for side effects following vaccination. Here, we expand on those findings, examining HLA variation for association with vaccine side effects in 6470 patients of European ancestry from the United States. In our cohort, ~30% of individuals experienced systemic side effects (e.g., fever, chills, headache) after their initial vaccination series, while that proportion climbed to >60% in individuals receiving booster doses. We confirm the association of HLA-A*03:01 with systemic side effects to COVID-19 vaccines, particularly the Pfizer-BioNTech vaccine (OR = 1.52 [95% CI 1.23-1.97], p = 0.002). We observed similar effect size of this allele in individuals reporting side effects from the initial series or boosters (OR = 1.25 [95% CI 1.15-1.53];p>0.0001), but comparatively higher effect size in individuals who subsequently experienced breakthrough infections (OR = 2.11 [95% CI 1.12-4.31];p = 0.04). Our results confirm prior reports regarding HLA association with vaccine side effects, and suggest that the immunopathology underlying the HLAA* 03:01 association with side effects may increase those individuals' propensity for breakthrough infections after vaccination. Our results highlight the need to explore the functional mechanisms underlying this association to improve vaccine design and implementation strategies against emergent SARS-CoV-2 variants.