The outcomes of cryptococcal disease in HIV-positive individuals following COVID-19 infection: A systematic review and meta-analysis

Background: Cryptococcal disease is considered a major cause of morbidity in individuals with HIV in resource-limited settings. The long-term effects of COVID-19 and cryptococcal coinfection among people living with HIV (PLWHIV) have not been thoroughly investigated. This study examined the incidence of cryptococcosis among HIV-positive individuals following COVID-19.

Methods: A thorough search was conducted across five databases on November 14, 2023, and updated on May 7, 2024. Observational and case reports on the clinical and pathological outcomes of cryptococcosis in HIV-positive individuals with COVID-19 were eligible. The authors extracted the study characteristics and main outcomes: mortality, prevalence, AIDS-defining diseases, combined cryptococcosis, and COVID-19 impact on hospitalization, in a standard Excel sheet.

Results: Of the 752 identified articles (40 in the initial search and six in the updated search), eight were selected. The minimum follow-up duration varied between the research periods, which was three months. The investigations comprised 5751 PLWHIV: 3830 were COVID-19-positive, 130 developed cryptococcosis, and two case reports revealed individuals with concomitant HIV, COVID-19, and cryptococcal infections. The meta-analysis pooled risk ratio (RR) for incidence was 0.21 (90 % confidence interval [CI]: 0.04–1.31) with high heterogeneity (I² = 98 %), while the pooled risk for mortality was 1.49 (95 % confidence interval: 0.60–3.72), with moderate heterogeneity (I² = 65 %). The chi-squared test for heterogeneity (X² = 125.62, p-value <0.00001) revealed considerable variation.

Conclusions: Cryptococcosis remains a rare but significant complication for PLWHIV following the COVID-19 infection. The data suggests a decrease in incidence risk while a probable increase in mortality. The observed heterogeneity and variability address the importance of enhanced surveillance and targeted interventions for this vulnerable population. Further research is essential to identify factors contributing to heterogeneity and develop effective strategies for managing cryptococcosis in PLWHIV.

• Epidemiology and Determinants of Health
  • Epidemiology
• Population(s)
  • General HIV+ population
• Prevention, Engagement and Care Cascade
  • Engagement and Care Cascade
• Engagement and Care Cascade
  • Treatment
• Co-infections
  • Other