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Hospital and Death Rate Almost Twice Higher After SARS-CoV-2 in Unvaccinated
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CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver
Mark Mascolini
Vaccinated people without prior SARS-CoV-2 infection and unvaccinated people with prior infection had similar protection against new infection, according to analysis of 28,000 US veterans by Adeel Butt (Weill-Cornell Medical College, New York) and colleagues at other centers [1]. But after reinfection, unvaccinated previously infected people ran almost a twice higher risk of hospital admission or death than vaccinated people with breakthrough infection.
Current SARS-CoV-2 vaccines offer strong protection against infection and severe, critical, or fatal disease, Butt noted. But this protection dwindles over time. Infection with the coronavirus induces immunity that protects against severe, critical, or fatal COVID, he added, but natural SARS-CoV-2 infection does not protect against reinfection.
These researchers previously reported a SARS-CoV-2 infection rate of 0.66 per 1000 person-days 7 or more days after a second vaccination in 410 US veterans [2]. Further analysis of 502,780 veterans who received two vaccine doses and 599,974 % confidence veterans who received no vaccine doses found an infection rate of 0.553 per 1000 person-day (95interval [CI] 0.452 to 0.676) in vaccinated people, less than half the rate in unvaccinated veterans, 1.224 per 1000 person-days (95% CI 1.066 to 1.406) [3].
The new analysis aimed to compare the incidence of hospital admission or death in veterans in the US Veterans Affairs (VA) COVID-19 database [1]. The researchers matched 13,976 vaccinated VA participants to 13,976 unvaccinated people for age, race, sex, diabetes, hypertension, chronic kidney disease, coronary artery disease, cancer diagnosis, chronic obstructive pulmonary disease, stroke, body mass index, calendar quarter of infection, and geographic location.
The matched groups each had 91% male populations with a median age of 56 years. Proportions of whites (80.5%) blacks (13.9%), and people of other or unknown race or ethnicity (5.5%) were the same in the matched vaccinated and unvaccinated groups. Just over half of each group (53.7%) had a body mass index indicating obesity. Marginally more unvaccinated veterans than vaccinated veterans had COVID symptoms at breakthrough infection or reinfection (31.05% vs 28.59%, P = 0.0539).
Incidence of reinfection in unvaccinated people (0.31 per 1000 person-days, 95% CI 0.30 to 0.32) almost overlapped the breakthrough rate in vaccinated people (0.30 per 1000 person-days, 95% CI 0.29 to 0.32) (P = 0.052). Infection incidence did differ between unvaccinated VA participants with reinfection and their vaccinated counterparts with breakthrough infection in those younger than 65 (0.33 vs 0.30 per 1000 person-days, P =0.03), age 65 or older (0.32 vs 0.24 per 1000 person-days, P < 0.001), body mass index at or below the obesity cutoff of 30 kg/m2 (0.33 vs 0.26 per 1000 person-days, P < 0.001), body mass index above 30 kg/m2 (0.29 vs 0.33 per 1000 person-days, P = 0.002), and Charlson comorbidity index above 2 (0.41 vs 0.35 per 1000 person-days, P = 0.04).
The unvaccinated reinfection group had a significantly higher incidence of hospital admission or death within 28 days than the vaccinated breakthrough infection group (7.31 vs 4.69 per 1000 person-days, P < 0.001). Hospital admission and death rates remained higher in unvaccinated than vaccinated cohort members in several subgroups: age under 65 (3.49 vs 2.76 per 1000 person-days, approaching significance at P = 0.08), age 65 or older (16.62 vs 12.14 per 1000 person-days, P = 0.01), male sex (8.17 vs 5.04 per 1000 person-days, P < 0.0001), white race (7.60 vs 4.90 per 1000 person-days, P < 0.001), black race (8.48 vs 4.55 per 1000 person-days, P = 0.01), body mass index at or below 30 kg/m2 (8.46 vs 5.00 per 1000 person-days, P < 0.0001), and body mass index above 30 kg/m2 (6.32 vs 4.48 per 1000 person-days, P = 0.004).
This analysis also found significantly higher hospital admission and death rates in people 65 or older versus younger people in both the vaccinated and unvaccinated groups, in men than in women in both groups, and in people with a body mass index at or below 30 mg/kg2 among unvaccinated reinfected people.
Butt and colleagues suggested several possible explanations for the higher hospital admission and death rates in reinfected unvaccinated people than in vaccinated people with breakthrough infection, despite similar SARS-CoV-2 infection rates: (1) Natural infection may have other consequences that vaccination prevents. (2) Vaccinated people may differ in behavior from unvaccinated people, for example, they may understand or adopt preventive measures better. (3) Vaccination may have still-undiscovered benefits.
References
1. Butt A, Yan P, Shaikh OS. COVID-19 incidence in persons with reinfection vs post-vaccination breakthrough infection. CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver. Abstract 132.
2. Butt AA, Yan P, Shaikh OS, Mayr FB. Outcomes among patients with breakthrough SARS-CoV-2 infection after vaccination in a high-risk national population. EClinicalMedicine. 2021:40:101117. doi: 10.1016/j.eclinm.2021.101117. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00397-7/fulltext
3. Butt AA, Yan P, Shaikh OS, Mayr FB, Omer SB. Rate and risk factors for severe/critical disease among fully vaccinated persons with breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a high-risk national population. Clin Infect Dis. 2022;75:e849-e856. doi: 10.1093/cid/ciab1023. https://academic.oup.com/cid/article/75/1/e849/6459161
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