Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods

Abstract

ImportanceRecent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination.ObjectivesTo evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of BA.4 or BA.5 predominant circulation; and to evaluate the relative severity of COVID-19 in hospitalized patients across Omicron BA.1, BA.2 or BA.2.12.1, and BA.4 or BA.5 sublineage periods.Design, Setting, and ParticipantsThis test-negative case-control study was conducted in 10 states with data from emergency department (ED) and urgent care (UC) encounters and hospitalizations from December 16, 2021, to August 20, 2022. Participants included adults with COVID-19–like illness and molecular testing for SARS-CoV-2. Data were analyzed from August 2 to September 21, 2022.ExposuresmRNA COVID-19 vaccination.Main Outcomes and MeasuresThe outcomes of interest were COVID-19 ED or UC encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. VE associated with protection against medically attended COVID-19 was estimated, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as the reference group). Among hospitalized patients with COVID-19, demographic and clinical characteristics and in-hospital outcomes were compared across sublineage periods.ResultsDuring the BA.4 and BA.5 predominant period, there were 82 229 eligible ED and UC encounters among patients with COVID-19–like illness (median [IQR] age, 51 [33-70] years; 49 682 [60.4%] female patients), and 19 114 patients (23.2%) had test results positive for SARS-CoV-2; among 21 007 hospitalized patients (median [IQR] age, 71 [58-81] years; 11 209 [53.4%] female patients), 3583 (17.1 %) had test results positive for SARS-CoV-2. Estimated VE against hospitalization was 25% (95% CI, 17%-32%) for receipt of 2 vaccine doses at 150 days or more after receipt, 68% (95% CI, 50%-80%) for a third dose 7 to 119 days after receipt, and 36% (95% CI, 29%-42%) for a third dose 120 days or more (median [IQR], 235 [204-262] days) after receipt. Among patients aged 65 years or older who had received a fourth vaccine dose, VE was 66% (95% CI, 53%-75%) at 7 to 59 days after vaccination and 57% (95% CI, 44%-66%) at 60 days or more (median [IQR], 88 [75-105] days) after vaccination. Among hospitalized patients with COVID-19, ICU admission or in-hospital death occurred in 21.4% of patients during the BA.1 period vs 14.7% during the BA.4 and BA.5 period (standardized mean difference: 0.17).Conclusions and RelevanceIn this case-control study of COVID-19 vaccines and illness, VE associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated VE was higher after receipt of 1 or 2 booster doses compared with a primary series alone.

Clinical and Imaging Characteristics of SARS-CoV-2 Breakthrough Infection in Hospitalized Immunocompromised Patients

“…Clinical factors, such as demographic characteristics, smoking history, vaccination status, history of prior SARS-CoV-2 infection, body mass index at admission, comorbidities, and clinical outcomes, were evaluated using the electronic medical records. Vaccination states were defined as the receipt of one or two vaccine doses ≥ 14 days before diagnosis [ 22 ], or more than 3 doses ≥ 7 days before diagnosis [ 23 ]. A history of prior SARS-CoV-2 infection was defined as a positive test result for the virus 45 days after recovery from a previous infection caused by the same or different viral strains.…”

Changes in life expectancy and life span equality during the COVID-19 epidemic in Japan up to 2022

“…The direct mortality impact of COVID-19 has been alleviated by these vaccines, but a substantial proportion of deaths are caused indirectly through complications such as cardiovascular disorders, or by limited access to healthcare services when the healthcare capacity or ambulance system were overwhelmed by the increased case load pressure of COVID-19. 5,[7][8][9][10][11][12][13][14][15] The ongoing emergence of SARS-CoV-2 variants with a high capability of immune evasion and transmission may have worsened the health impact of COVID-19, but understanding the true burden has remained a challenging task. 16,17 Direct approaches to estimating the mortality impact of COVID-19 are therefore challenging, including in Japan.…”

Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)

“…The standard of care for COVID-19 evolved to include targets for both viral replication as well as host inflammatory responses 5 6. Combined with vaccination, widespread natural infection and the emergence of less virulent SARS-CoV-2 variants, the severity of COVID-19 has decreased and outcomes have improved 7. However, SARS-CoV-2 has continued to circulate globally, but in contrast to the early waves of the pandemic, severe COVID-19 infection now primarily occurs in immunocompromised, comorbid and elderly patients 7–9…”