Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients

Abstract

Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19.Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile.Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay.Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels.Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention.Clinical Trial Registration:ClinicalTrials.gov identifier NCT04343053.

Increased sHLA-G Is Associated with Improved COVID-19 Outcome and Reduced Neutrophil Adhesion

“…The study aimed to prospectively evaluate the pro-thrombotic status and systemic inflammatory biomarkers in moderate-to-severe COVID-19 patients and to correlate these biomarkers with clinical outcomes (Clinicaltrials.gov identifier NCT04343053). The design of the study has been described in detail in previous reports [ 24 , 25 , 26 ]. Briefly, patients were included if they had SARS-COV2 infection (confirmed by PCR-positive nasopharyngeal swab specimens) and respiratory failure (defined as arterial oxygen tension of <8.0 kPa (60 mmHg) at room air and oxygen saturation < 90%).…”

EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

“…Cytokines associating with EASIX and outcome of post-transplant complications include ANG2, sCD141, ST2 ( 19 , 20 , 29 ), CXCL9 ( 30 ) and IL18 ( 31 , 32 ). Interferon-alpha represents an early but transient immune response to viral infections that appeared deficient in COVID-19 patients ( 33 ). ANG2 and other endothelial serum markers were already shown to predict severe clinical courses of COVID-19 ( 16 , 34 ).…”

A model of the innate immune response to SARS-CoV-2 in the alveolar epithelium

“…Since SARS-CoV-2 has evolved mechanisms for inhibiting interferon (IFN) production, and some research suggests that select immune cells are specially equipped to produce type I interferons [74], our baseline simulation neglected epithelial-cell IFN production. However, since SARS-CoV-infected alveolar epithelial cells were found to produce type I IFN mRNA in vitro, and individual differences in IFN signalling may partially explain variability in the severity of COVID-19 symptoms [97][98][99], it is interesting to consider how epithelial-cell IFN production may impact the course of infection. Figure 6 shows that epithelial-cell IFN production results in a significantly faster IFN response and a marginal increase in maximal IFN levels.…”