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

## TL;DR

This study examines how nicotine exposure affects immune responses in hospitalized COVID-19 patients through blood and urine analysis.

## Contribution

The study identifies distinct immunological profiles in nicotine-exposed hospitalized COVID-19 patients using serum cotinine as a biomarker.

## Key findings

- Nicotine-exposed patients showed lower IgA and IgM levels at specific time points compared to non-exposed individuals.
- Urine immunological profiles showed minimal overlap with blood profiles and unique marker changes in nicotine-exposed patients.
- Nicotine-exposed patients had elevated HMGB-1 at admission but no increased non-specific inflammation markers.

## Abstract

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.