Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

Whole Blood Reactivity to Viral and Bacterial Pathogens after Non-Emergent Cardiac Surgery during the Acute and Convalescence Periods Demonstrates a Distinctive Profile of Cytokines Production Compared to the Preoperative Baseline in Cohort of 108 Patients, Suggesting Immunological Reprogramming during the 28 Days Traditionally Recognized as the Post-Surgical Recovery Period.

The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (tbaseline), followed by subsequent challenges during the acute phase (t24h), convalescence (t7d), and long-term recovery (t3m). For 108 patients undergoing elective heart surgery, whole blood was stimulated with lipopolysaccharide (LPS), Influenza A virus subtype N2 (H3N2), or the Flublok™ vaccine to represent common pathogenic challenges. Leukocytosis, platelet count, and serum C-reactive protein (CRP) were used to measure non-specific inflammation. Cytokines were measured after 18 h of stimulation to reflect activation of the various cell types (activated neutrophils-IL-8; activated T cells-IL-2, IFNγ, activated monocyte (MO)-TNFα, IL-6, and deactivated or atypically activated MO and/or T cells-M-CSF, IL-10). IL-2 and IL-10 were increased at t7d, while TNFα was suppressed at t24h when LPS was utilized. Interestingly, M-CSF and IL-6 production was elevated at seven days in response to all stimuli compared to baseline. While some non-specific markers of inflammation (white cell count, IL-6, and IL-8) returned to presurgical levels at t3m, CRP and platelet counts remained elevated. We showed that surgical stimulus reprograms leukocyte response to LPS with only partial restoration of non-specific markers of inflammation.