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 down arrow), 48 h (CCL19 down arrow, MCP-3 down arrow, CD28 up arrow, CD8 down arrow, IFN gamma down arrow, IL-12 down arrow, GZNB down arrow, MIC A/B down arrow) or 7 days (CD28 down arrow) 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 up arrow, CXCL5 up arrow, CD8 up arrow, IL-12 up arrow, MIC A/B up arrow, GZNH up arrow, TNFRS14 up arrow), t48h (CCL20 down arrow, TRAIL down arrow) and t7d (EGF up arrow, ADA up arrow) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.