Autoantibodies to Interferons in Infectious Diseases.

Anti-cytokine autoantibodies and, in particular, anti-type I interferons are increasingly described in association with immunodeficient, autoimmune, and immune-dysregulated conditions. Their presence in otherwise healthy individuals may result in a phenotype characterized by a predisposition to infections with several agents. For instance, anti-type I interferon autoantibodies are implicated in Coronavirus Disease 19 (COVID-19) pathogenesis and found preferentially in patients with critical disease. However, autoantibodies were also described in the serum of patients with viral, bacterial, and fungal infections not associated with COVID-19. In this review, we provide an overview of anti-cytokine autoantibodies identified to date and their clinical associations; we also discuss whether they can act as enemies or friends, i.e., are capable of acting in a beneficial or harmful way, and if they may be linked to gender or immunosenescence. Understanding the mechanisms underlying the production of autoantibodies could improve the approach to treating some infections, focusing not only on pathogens, but also on the possibility of a low degree of autoimmunity in patients.

Lack of a prompt normalization of immunological parameters is associated with long-term care and poor prognosis in COVID-19 affected patients receiving convalescent plasma: a single center experience.

OBJECTIVES: Being COVID-19 convalescent plasma (CCP) a therapeutic option that can have a potential impact on the normalization of immunological parameters of COVID-19 affected patients, a detailed analysis of post-infusion immunological changes was conducted in CCP treated patients, aiming to identify possible predictive hallmarks of disease prognosis. METHODS: This prospective observational study describes a cohort of 28 patients who received CCP shortly after being hospitalized for COVID-19 and diagnosed for Acute Respiratory Distress Syndrome. All patients were subjected to a detailed flow cytometry based evaluation of immunological markers at baseline and on days +3 and +7 after transfusion. RESULTS: At baseline almost all patients suffered from lymphopenia (25/28 on T-cells and 16/28 on B-cells) coupled with neutrophil-lymphocyte ratio exceeding normal values (26/28). Lymphocyte subsets were generally characterized by increased percentages of CD19+CD20-CD38hiCD27+ plasmablasts and reduction of CD4+CD45RA+CCR7+CD31+ recent thymic emigrants, while monocytes presented a limited expression of CD4 and HLA-DR molecules. Amelioration of immunological parameters began to be evident from day +3 and became more significant at day +7 post-CCP transfusion in 18 patients who recovered within 30 days from hospitalization. Conversely, baseline immunological characteristics generally persisted in ten critical patients who eventually progressed to death (6) or long-term care (4). CONCLUSIONS: This study demonstrates that proper immunophenotyping panels can be potentially useful for monitoring CCP treated patients from the first days after infusion in order to presume higher risk of medical complications.

Long pentraxin 3 as a marker of COVID-19 severity: evidences and perspectives.

Introduction: Several laboratory tests are characteristically altered in Coronavirus Disease 2019 (COVID-19), but are not totally accurate in predicting the disease outcome. The long pentraxin 3 (PTX3) is quickly released directly at inflammation sites by many immune cell types. Previous studies have shown that PTX3 correlated with disease severity in various inflammatory conditions. Our study investigated the use of PTX3 as a potential marker of COVID-19 severity and compared its performance in detecting a more severe form of the disease with that of routine laboratory parameters. Materials and methods: Stored serum samples of RT-PCR confirmed COVID-19 cases that had been obtained at hospital admission were retrospectively analysed. Intensive care unit (ICU) stay was considered a surrogate endpoint of severe COVID-19. Pentraxin 3 was measured by a commercial enzyme-linked immunosorbent assay. Results: A total of 96 patients were recruited from May 1st, 2020 to June 30th, 2020; 75/96 were transferred to ICU. Pentraxin 3 was higher in ICU vs non-ICU patients (35.86 vs 10.61 ng/mL, P < 0.001). Univariate and multivariate logistic regression models demonstrated that the only significant laboratory predictor of ICU stay was PTX3 (OR: 1.68 (1.19-2.29), P = 0.003), after controlling for comorbidities. The Receiver Operator Characteristic curve analysis showed that PTX3 had a higher accuracy compared to C-reactive protein (CRP), lactate dehydrogenase (LD), ferritin in identifying ICU patients (AUC of PTX3 = 0.98; CRP = 0.66; LD = 0.70; ferritin = 0.67, P < 0.001). A cut-off of PTX3 > 18 ng/mL yielded a sensitivity of 96% and a specificity of 100% in identifying patients requiring ICU. Conclusion: High values of PTX3 predict a more severe COVID-19.