A Retrospective, Monocentric Study Comparing Co and Secondary Infections in Critically Ill COVID-19 and Influenza Patients.

Few data are available on infectious complications in critically ill patients with different viral infections. We performed a retrospective monocentric study including all of the patients admitted to the intensive care unit (ICU) with confirmed COVID-19 (as of 13 March 2020) or Influenza A and/or B infections (as of 1 January 2015) until 20 April 2020. Coinfection and secondary infections (occurring within and after 48 h from admission, respectively) were recorded. Fifty-seven COVID-19 and 55 Influenza patients were included. Co-infections were documented in 13/57 (23%) COVID-19 patients vs. 40/55 (73%) Influenza patients (p < 0.001), most of them being respiratory (9/13, 69% vs. 35/40, 88%; p = 0.13) and of bacterial origin (12/13, 92% vs. 29/40, 73%; p = 0.25). Invasive aspergillosis infections were observed only in Influenza patients (8/55, 15%). The COVID-19 and Influenza patients presented 1 (0−4) vs. 0 (0−4) secondary infections (p = 0.022), with comparable sites being affected (lungs: 35/61, 57% vs. 13/31, 42%; p = 0.16) and causative pathogens occurring (Gram-negative bacteria: 51/61, 84% vs. 23/31, 74%; p > 0.99). The COVID-19 patients had longer ICU lengths of stay (15 (−65) vs. 5 (1−89) days; p = 0.001), yet the two groups had comparable mortality rates (20/57, 35% vs. 23/55, 41%; p = 0.46). We report fewer co-infections but more secondary infections in the ICU COVID-19 patients compared to the Influenza patients. Most of the infectious complications were respiratory and of bacterial origin.

Cross-Sectional Evaluation of Humoral Responses against SARS-CoV-2 Spike.

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike.

The SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoprotein of SARS-CoV-2 mediates viral entry and is the main target for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic and public health interventions. Here we performed a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against the SARS-CoV-2 Spike. The vast majority of infected individuals elicited anti-Spike antibodies within 2 weeks after the onset of symptoms. The levels of receptor-binding domain (RBD)-specific IgG persisted overtime, while the levels of anti-RBD IgM decreased after symptoms resolution. Some of the elicited antibodies cross-reacted with other human coronaviruses in a genus-restrictive manner. While most of individuals developed neutralizing antibodies within the first two weeks of infection, the level of neutralizing activity was significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

BRCA gene mutations do not shape the extent and organization of tumor infiltrating lymphocytes in triple negative breast cancer.

This study investigated the prevalence of TIL subpopulations, TLS, PD-1 and PD-L1 in tumors from TNBC patients harboring wild-type or mutated BRCA1 or BRCA2 germline genes. This TNBC cohort included 85% TIL-positive (≥10%) tumors with 21% classified as TILhi (≥50%). Interestingly, the BRCAmut group had a significantly higher incidence of TILpos tumors compared to the BRCAwt group (P = 0.037). T cells were dominant in the infiltrate but no statistically significant differences were detected between BRCAwt and BRCAmut for CD3+, CD4+ and CD8+ T cells or CD20+ B cells. TLS were detected in 74% of tumors but again no significant differences between the BRCA groups. PD-1 expression was observed in 33% and PD-L1 in 53% (any cell, cut-off ≥1%) tumors for the entire TNBC cohort. PD-1 expression correlated with PD-L1 and both with TIL and TLS but was not associated with BRCA mutational status. Our analyses reveal that BRCAwt and BRCAmut TNBC are similar except for a significant increase of TILpos tumors in the BRCAmut group. While BRCA gene mutations may not directly drive immune infiltration, the greater number of TILpos tumors could signal greater immunogenicity in this group.