Factors Associated With Severe COVID-19 Among Vaccinated Adults Treated in US Veterans Affairs Hospitals

Abstract

ImportanceWith a large proportion of the US adult population vaccinated against SARS-CoV-2, it is important to identify who remains at risk of severe infection despite vaccination.ObjectiveTo characterize risk factors for severe COVID-19 disease in a vaccinated population.Design, Setting, and ParticipantsThis nationwide, retrospective cohort study included US veterans who received a SARS-CoV-2 vaccination series and later developed laboratory-confirmed SARS-CoV-2 infection and were treated at US Department of Veterans Affairs (VA) hospitals. Data were collected from December 15, 2020, through February 28, 2022.ExposuresDemographic characteristics, comorbidities, immunocompromised status, and vaccination-related variables.Main Outcomes and MeasuresDevelopment of severe vs nonsevere SARS-CoV-2 infection. Severe disease was defined as hospitalization within 14 days of a positive SARS-CoV-2 diagnostic test and either blood oxygen level of less than 94%, receipt of supplemental oxygen or dexamethasone, mechanical ventilation, or death within 28 days. Association between severe disease and exposures was estimated using logistic regression models.ResultsAmong 110 760 patients with infections following vaccination (97 614 [88.1%] men, mean [SD] age at vaccination, 60.8 [15.3] years; 26 953 [24.3%] Black, 11 259 [10.2%] Hispanic, and 71 665 [64.7%] White), 10 612 (9.6%) had severe COVID-19. The strongest association with risk of severe disease after vaccination was age, which increased among patients aged 50 years or older with an adjusted odds ratio (aOR) of 1.42 (CI, 1.40-1.44) per 5-year increase in age, such that patients aged 80 years or older had an aOR of 16.58 (CI, 13.49-20.37) relative to patients aged 45 to 50 years. Immunocompromising conditions, including receipt of different classes of immunosuppressive medications (eg, leukocyte inhibitor: aOR, 2.80; 95% CI, 2.39-3.28) or cytotoxic chemotherapy (aOR, 2.71; CI, 2.27-3.24) prior to breakthrough infection, or leukemias or lymphomas (aOR, 1.87; CI, 1.61-2.17) and chronic conditions associated with end-organ disease, such as heart failure (aOR, 1.74; CI, 1.61-1.88), dementia (aOR, 2.01; CI, 1.83-2.20), and chronic kidney disease (aOR, 1.59; CI, 1.49-1.69), were also associated with increased risk. Receipt of an additional (ie, booster) dose of vaccine was associated with reduced odds of severe disease (aOR, 0.50; CI, 0.44-0.57).Conclusions and RelevanceIn this nationwide, retrospective cohort of predominantly male US Veterans, we identified risk factors associated with severe disease despite vaccination. Findings could be used to inform outreach efforts for booster vaccinations and to inform clinical decision-making about patients most likely to benefit from preexposure prophylaxis and antiviral therapy.

Ocular Vascular Events following COVID-19 Vaccines: A Systematic Review

“…Our cohort had a mean age of 58.92 ± 17.57, falling within the older age group. Age above 50 years was linked to COVID vaccine-related adverse events [39,65], and ocular vascular events were recorded in the same age group in [64]. This was also true when comparing ischemic optic neuropathy versus optic neuritis in patients that developed optic neuropathy after COVID-19 vaccination [61].…”

Attributable Causes of Death Among US Veteran Patients within 30-90 days following SARS-CoV-2 Infection: A Nationwide Cohort Study

“…Focusing on conditions identi ed as signi cantly associated with risk of severe COVID-19 despite vaccination (aOR > 1.5), 9 dementia (14.4%), chronic kidney disease (28.0%), chronic obstructive pulmonary disease (COPD)(14.6%), and heart failure (20.2%) were all common. 23.2% had advanced cancer, and 1.6% had had organ transplantation.…”

“…In our previous study, a review of 40 deaths during the period of predominance of the delta variant indicated that COVID-19 was the cause of death in over 75% of cases even if the ICD-10 codes for COVID-19 were not associated with the hospitalization. 9 Similarly, a chart-based study of 100 deaths during hospitalization with a concomitant positive SARS-CoV-2 test in a single US center in 2020 found that at least 85% of cases were attributable to COVID-19, but the ICD-10 code was used in only 75% of those cases. 5 We are not aware of any further studies that have used chart review to distinguish SARS-CoV-2 as a cause, contributor, or non-contributor, but our nding of a rising percentage of "contributory" cases among COVID-related deaths is consistent with recent CDC data.…”

“…Although a slightly different question was asked, the similarities in ndings of risk of severe disease in the VA population and a large UK study are encouraging for our results being applicable to other settings. 14,9 Periodic repetition of the process of adjudication by chart review will be needed as new variants arise and as additional therapeutic and preventative measures become available. Because many risk factors for death due to COVID-19 despite vaccination (age, dementia, heart failure, COPD, CKD) are also risk factors for death from other causes, we are skeptical that an algorithm will provide attribution as good as physician assessment.…”

Errors in Methods Section and Supplement

“…In the Original Investigation titled “Factors Associated With Severe COVID-19 Among Vaccinated Adults Treated in US Veterans Affairs Hospitals,” 1 published October 20, 2022, there were errors in the Methods section and online-only Supplement. The period of data collection for comorbidities started December 15, 2020, and concluded at the time of vaccination.…”