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.

Is coagulation-protein consumption upon admission linked to COVID-19 severity and mortality? (preprint)

ABSTRACT The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. With the aim of evaluating the association of several coagulation proteins with COVID-19 severity and mortality, we performed a cross-sectional study in 134 patients classified according to the highest disease severity reached during the disease. We found higher levels of antithrombin, prothrombin, factor XI, factor XII and factor XIII in asymptomatic/mild and moderate COVID-19 patients than healthy individuals. Interestingly, decreased levels of antithrombin, factor XI, XII and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. In conclusion, COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might “paradoxically” imply a higher risk of progression to severe disease and COVID-19-related mortality.