Analysis of Severe Illness After Postvaccination COVID-19 Breakthrough Among Adults With and Without HIV in the US

Abstract

Understanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations.

Objective

To estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection.

Design, Setting, and Participants

In this cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible.

Exposures

HIV infection.

Main Outcomes and Measures

The main outcome was severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status.

Results

Among 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, −0.67%; 95% CI, −2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/μL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P = .049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status.

Conclusions and Relevance

In this cohort study, the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies.

SciScore for 10.1101/2022.04.15.22273913: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IRB: This collaboration is an extension of the North American AIDS Cohort Collaboration on Research and Design.26 Each local institution and the Johns Hopkins Bloomberg School of Public Health institutional review board granted approval.
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.

Table 2: Resources

No key resources detected.

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

Limitations: Our findings may not be generalizable to all PWH, as our study population had a greater proportion of males (89%) than found in the US population of PWH, and those with higher barriers to accessing healthcare (who may be at greater risk for COVID-19) were less likely to be included in our study population. Other outcome data, including mechanical ventilation and death (particularly if death occurred out of hospital) may be under-ascertained. The discharge diagnosis ranking was not consistent as one cohort was only able to provide the primary diagnosis with the remainder unranked; however, a sensitivity analyses demonstrated no significant differences in results following exclusion of this cohort. All discharge diagnoses were reviewed by clinicians to increase specificity in our classification of COVID-19 hospitalization, but discharge coding can be influenced by many factors including reimbursement practices. Similarly, our matching schema was not consistent, but the distributions of matching factors indicate that our sample of PWH and PWoH were comparable; we included the matching factors in multivariable analyses to address residual confounding. Conclusions: It was uncommon for COVID-19 breakthrough illness to progress to severe illness in our population of PWH and PWoH; however, PWH with moderate immune suppression (200-349 cells/mm3) had an increased severe COVID-19 breakthrough illness risk (compared to PWoH) and may benefit from being included in the CDC’s ...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

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