Expression profile of HERVs and inflammatory mediators detected in nasal mucosa as a predictive biomarker of COVID-19 severity.

Introduction: Our research group and others demonstrated the implication of the human endogenous retroviruses (HERVs) in SARS-CoV-2 infection and their association with disease progression, suggesting HERVs as contributing factors in COVID-19 immunopathology. To identify early predictive biomarkers of the COVID-19 severity, we analyzed the expression of HERVs and inflammatory mediators in SARS-CoV-2-positive and -negative nasopharyngeal/oropharyngeal swabs with respect to biochemical parameters and clinical outcome. Methods: Residuals of swab samples (20 SARS-CoV-2-negative and 43 SARS-CoV-2-positive) were collected during the first wave of the pandemic and expression levels of HERVs and inflammatory mediators were analyzed by qRT-Real time PCR. Results: The results obtained show that infection with SARS-CoV-2 resulted in a general increase in the expression of HERVs and mediators of the immune response. In particular, SARS-CoV-2 infection is associated with increased expression of HERV-K and HERV-W, IL-1ß, IL-6, IL-17, TNF-α, MCP-1, INF-γ, TLR-3, and TLR-7, while lower levels of IL-10, IFN-α, IFN-ß, and TLR-4 were found in individuals who underwent hospitalization. Moreover, higher expression of HERV-W, IL-1ß, IL-6, IFN-α, and IFN-ß reflected the respiratory outcome of patients during hospitalization. Interestingly, a machine learning model was able to classify hospitalized vs not hospitalized patients with good accuracy based on the expression levels of HERV-K, HERV-W, IL-6, TNF-a, TLR-3, TLR-7, and the N gene of SARS-CoV-2. These latest biomarkers also correlated with parameters of coagulation and inflammation. Discussion: Overall, the present results suggest HERVs as contributing elements in COVID-19 and early genomic biomarkers to predict COVID-19 severity and disease outcome.

T Lymphocyte Subset Counts and Interferon-Gamma Production in Adults and Children with COVID-19: A Narrative Review.

Adults and children exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with minimal to mild symptoms, especially in the pediatric age. However, some children present with a severe hyperinflammatory post-infectious complication named multisystem inflammatory syndrome in children (MIS-C), mainly affecting previously healthy subjects. Understanding these differences is still an ongoing challenge, that can lead to new therapeutic strategies and avoid unfavorable outcomes. In this review, we discuss the different roles of T lymphocyte subsets and interferon-γ (IFN-γ) in the immune responses of adults and children. Lymphopenia can influence these responses and represent a good predictor for the outcome, as reported by most authors. The increased IFN-γ response exhibited by children could be the starting point for the activation of a broad response that leads to MIS-C, with a significantly higher risk than in adults, although a single IFN signature has not been identified. Multicenter studies with large cohorts in both age groups are still needed to study SARS-CoV-2 pathogenesis with new tools and to understand how is possible to better modulate immune responses.

A retrospective study on COVID-19 in a tertiary care rural hospital

Background: Coronavirus disease 2019 (COVID-19) has rapidly become a worldwide concern ever since first being reported from Wuhan, China in December 2019. With no known cure, there is widespread fear-provoking interest in studying the factors contributing to mortality. Aim and Objectives: The current study was undertaken with a view to try to understand the cause of morbidity and mortality. Materials and Methods: A retrospective study done in our Institution on COVID-19 patients admitted over a course of 3 months after approval from Institutional Ethics Committee. Results: We had 17 deaths over the period under consideration whereas 73 patients improved (mortality = 19%, n = 90). Most of the patients were in the 41–80 years age group (>70%). No gender preponderance was found with mortality in each being around 20%. A clear correlation between co-morbidities and mortality was found with no person without any comorbidity succumbing to the disease. Respiratory and Heart conditions were found to contribute most to mortality with patients presenting with shortness of breath being most at risk. Similarly, a Neutrophil: Lymphocyte ratio greater than 12 was found to significantly increase the mortality. Conclusion: Patients with comorbidities need to be monitored closely with treatment being directed at improving the respiratory outcome.

Congenital lung malformation patients experience respiratory infections after resection: A population-based cohort study.

PURPOSE: The benefit of elective resection of congenital lung malformations continues to be debated. Proponents of resection endorse a decreased risk of respiratory complications as one indication for surgery. Our study aimed to compare the prevalence of respiratory infections in cases, before and after resection of congenital lung malformations, to controls without a history of congenital lung malformation. METHODS: We performed a retrospective cohort study of children born from 1991 to 2007 who underwent congenital lung malformation resection. Patients were identified from Winnipeg´s Surgical Database of Outcomes and Management (WiSDOM), and a 10:1 date-of-birth matched control group was generated from a population-based administrative data repository. International Classification of Disease codes were used to assess pulmonary infection outcomes. Relative rates (RR) were calculated to compare the frequency of pneumonia, respiratory infections and influenza between cases and controls. RESULTS: We included 31 congenital lung malformation cases and 310 controls. Cases consisted of 14 (45.16%) congenital pulmonary airway malformations, 9 (29.03%) bronchopulmonary sequestrations and 8 (25.81%) hybrid lesions. Before resection, pneumonia was more common in cases than controls (RR 6.85; 95%CI 3.89, 11.9), while the risk of acute respiratory infections (RR 1.21; 95%CI 0.79, 1.79) and influenza (RR 0.46; 95%CI 0.01, 3.22) were similar to controls. Post-resection, the risk of pneumonia (RR 9.75; 5.06, 18.50) was still higher in cases than controls, and respiratory infections (RR 1.77; 95%CI 1.20, 2.53) and influenza (RR 3.98; 95%CI 1.48, 9.36) were more common in cases than controls. CONCLUSION: Our study demonstrated that after resection of congenital lung malformations, children experience more frequent respiratory infections compared to the general population. Resection does not eliminate the increased risk of pneumonia.

High CD169 Monocyte/Lymphocyte Ratio Reflects Immunophenotype Disruption and Oxygen Need in COVID-19 Patients.

BACKGROUND: Sialoadhesin (CD169) has been found to be overexpressed in the blood of COVID-19 patients and identified as a biomarker in early disease. We analyzed CD169 in the blood cells of COVID-19 patients to assess its role as a predictive marker of disease progression and clinical outcomes. METHODS: The ratio of the median fluorescence intensity of CD169 between monocytes and lymphocytes (CD169 RMFI) was analyzed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HDs) and correlated with immunophenotyping, inflammatory markers, cytokine mRNA expression, pulmonary involvement, and disease progression. RESULTS: CD169 RMFI was high in COV but not in HDs, and it correlated with CD8 T-cell senescence and exhaustion markers, as well as with B-cell maturation and differentiation in COV. CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients who were untreated at sampling, and was associated with the respiratory outcome throughout hospitalization. Finally, we also report the first evidence of the specific ability of the spike protein of SARS-CoV-2 to trigger CD169 RMFI in a dose-dependent manner in parallel with IL-6 and IL-10 gene transcription in HD PBMCs stimulated in vitro. CONCLUSION: CD169 is induced by the spike protein and should be considered as an early biomarker for evaluating immune dysfunction and respiratory outcomes in COVID-19 patients.

Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients.

BACKGROUND: Despite an impressive effort in clinical research, no standard therapeutic approach for coronavirus disease 2019 (COVID-19) patients has been established, highlighting the need to identify early biomarkers for predicting disease progression and new therapeutic interventions for patient management. The present study aimed to evaluate the involvement of the human endogenous retrovirus -W envelope (HERV-W ENV) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection considering recent findings that HERVs are activated in response to infectious agents and lead to various immunopathological effects. We analysed HERV-W ENV expression in blood cells of COVID-19 patients in correlation with clinical characteristics and have discussed its potential role in the outcome of the disease. METHODS: We analysed HERV-W ENV expression in blood samples of COVID-19 patients and healthy donors by flow cytometry and quantitative reverse transcriptase PCR analysis, and evaluated its correlation with clinical signs, inflammatory markers, cytokine expression, and disease progression. FINDINGS: HERV-W ENV was highly expressed in the leukocytes of COVID-19 patients but not in those of healthy donors. Its expression correlated with the markers of T-cell differentiation and exhaustion and blood cytokine levels. The percentage of HERV-W ENV-positive lymphocytes correlated with inflammatory markers and pneumonia severity in COVID-19 patients. Notably, HERV-W ENV expression reflects the respiratory outcome of patients during hospitalization. INTERPRETATION: Given the known immuno- and neuro-pathogenicity of HERV-W ENV protein, it could promote certain pathogenic features of COVID-19 and therefore serve as a biomarker to predict clinical progression of disease and open to further studies for therapeutic intervention. FUNDING: Information available at the end of the manuscript.