Changes in the senescence profile and immune checkpoints in HIV-infected individuals after COVID-19 (preprint)

Background: Both SARS-CoV-2 and HIV infection exhibit alterations in the senescence profile and immune checkpoint (IC) molecules. However, the midterm impact of SARS-CoV-2 on these profiles in people with HIV (PWH) remains unclear. This study aimed to evaluate differences in plasma biomarker levels related to ICs, the senescence-associated secretory phenotype (SASP), and pro- and anti-inflammatory cytokines in PWH following recovery from SARS-CoV-2 infection. Methods: We conducted a cross-sectional study of 95 PWH receiving antiretroviral therapy, stratified by SARS-CoV-2 infection status: a) 48 previously infected (HIV/SARS) and b) 47 controls without previous infection (HIV). Plasma biomarkers (n=44) were assessed using Procartaplex Multiplex Immunoassays. Differences were analyzed using a generalized linear model adjusted for sex and ethnicity and corrected for the false discovery rate. Significant values were defined as an adjusted arithmetic mean ratio [≥]1.2 or [≤]0.8 and a qvalue<0.1. Spearman correlation evaluated relationships between plasma biomarkers (significant correlations, rho[≥]0.3 and q value<0.1). Results: The median age of the PWH was 45 years, and 80% were men. All SARS-CoV-2-infected PWH experienced symptomatic infection; 83.3% had mild symptomatic infection, and sample collection occurred at a median of 12 weeks postdiagnosis. The HIV/SARS group showed higher levels of ICs (CD80, PDCD1LG2, CD276, PDCD1, CD47, HAVCR2, TIMD4, TNFRSF9, TNFRSF18, and TNFRSF14), SASP (LTA, CXCL8, and IL13), and inflammatory plasma biomarkers (IL4, IL12B, IL17A, CCL3, CCL4, and INF1A) than did the HIV group. Conclusions: SARS-CoV-2 infection in PWH causes significant midterm disruptions in plasma ICs and inflammatory cytokine levels, highlighting SASP-related factors, which could be risk factors for the emergence of complications in PWH.

Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses (preprint)

Background: shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. Methods: We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 hours of the first dose of remdesivir. Results: In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p=0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p=0.024). Conclusion: For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.