Interplay of Antibody and Cytokine Production Reveals CXCL13 as a Potential Novel Biomarker of Lethal SARS-CoV-2 Infection.

The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess the interplay of antibodies with the cytokine response in SARS-CoV-2 patients. We demonstrate that significant levels of anti-SARS-CoV-2 antibody to receptor binding domain (RBD), nucleocapsid, and spike S1 subunit of SARS-CoV-2 develop over the first 10 to 20 days of infection. The majority of patients produced antibodies against all three antigens (219/255 SARS-CoV-2+ patient specimens, 86%), suggesting a broad response to viral proteins. Antibody levels to SARS-CoV-2 antigens were different based on patient mortality, sex, blood type, and age. Analyses of these findings may help explain variation in immunity between these populations. To better understand the systemic immune response, we analyzed the levels of 20 cytokines by SARS-CoV-2 patients throughout infection. Cytokine analysis of SARS-CoV-2+ patients exhibited increases in proinflammatory markers (interleukin 6 [IL-6], IL-8, IL-18, and gamma interferon [IFN-γ]) and chemotactic markers (IP-10 and eotaxin) relative to healthy individuals. Patients who succumbed to infection produced decreased IL-2, IL-4, IL-12, RANTES, tumor necrosis factor alpha (TNF-α), GRO-α, and MIP-1α relative to patients who survived infection. We also observed that the chemokine CXCL13 was particularly elevated in patients who succumbed to infection. CXCL13 is involved in B cell activation, germinal center development, and antibody maturation, and we observed that CXCL13 levels in blood trended with anti-SARS-CoV-2 antibody levels. Furthermore, patients who succumbed to infection produced high CXCL13 and had a higher ratio of nucleocapsid to RBD antibodies. This study provides insights into SARS-CoV-2 immunity implicating the magnitude and specificity of response in relation to patient outcomes.IMPORTANCE The SARS-CoV-2 pandemic is continuing to impact the global population, and knowledge of the immune response to COVID-19 is still developing. This study assesses the interplay of different parts of the immune system during COVID-19 disease. We demonstrate that COVID-19 patients produce antibodies to three proteins of the COVID-19 virus (SARS-CoV-2) and identify many other immunological proteins that are involved during infection. The data suggest that one of these proteins (CXCL13) may be a novel biomarker for severe COVID-19 that can be readily measured in blood. This information combined with our broad-scale analysis of immune activity during COVID-19 provides new information on the immunological response throughout the course of disease and identifies a novel potential marker for assessing disease severity.

Advanced endotracheal tube biofilm stage, not duration of intubation, is related to pneumonia.

BACKGROUND: Biofilms are complex communities of living bacteria surrounded by a protective glycocalyx. Biofilms have been implicated in the development of infections such as dental caries and hardware infections. Biofilms form on endotracheal tubes (ETT) and can impact airway resistance. The lifecycle of a biofilm has four stages. We hypothesize that there is a relationship between the stage of biofilm on the ETT and development of pneumonia. METHODS: Thirty-two ETT were analyzed for biofilms and staged. Staging was performed by a microbiologist blinded to all patient information. Data included development of pneumonia, duration of intubation, comorbidities, and microbiology. Pneumonia was defined as presence of fever, WBC >12 K or <4 K, infiltrate on chest X-ray, and purulent sputum with +lower airway culture (bronchoalveolar lavage or brush). Statistics were performed by a biostatistician; p < 0.05 defined significance. RESULTS: There were 11 women and 21 men with a mean age of 50 years. Mean intensive care unit days were 13 (standard deviation ± 9.9) and mean length of intubation was 7.4 days (standard deviation ± 5.0). Half (16 of 32) the patients developed pneumonia while intubated. Eight of 10 patients with a stage IV biofilm had pneumonia. There was a relationship between increasing biofilm stage with the incidence of pneumonia (p < 0.05). Stage IV biofilms were associated with pneumonia (p < 0.02). There was no relationship to duration of intubation, patient age or hospital stay and biofilm stage. CONCLUSIONS: Advanced biofilm stage (stage IV) is associated with pneumonia. Duration of intubation does not predict biofilm stage.