The immune system’s response to an invading pathogen is the critical determinant in recovery from illness. Here, we hypothesize that the immune response will swiftly follow classical activation and a resolution trajectory in patients with the rapid evolution of symptoms if challenged by a viral pathogen for the first time. Alternatively, a dysregulated response will be signified by a protracted clinical trajectory. Consequently, we enrolled 106 patients during the first wave of COVID-19 and collected their blood within 24 h, 48 h, 7 days, and over 28 days from symptoms onset. The pathogenic burden was measured via serum levels of the S-spike protein and specific immunoglobulin titers against the S and N proteins of SARS-CoV-2. The nonspecific immunological response was gauged using interleukin 6, leukocytosis, and C-reactive protein. Coagulation status was assessed. Several serum biomarkers were used as surrogates of clinical outcomes. We identified four clusters depending on the onset of symptoms (immediate [A], 6 days [B], 12 days [C], and over 21 days [D]). High variability in the S-spike protein in cluster A was present. The corresponding immunoglobulin titer was random. Only procalcitonin differentiated clusters in terms of markers of nonspecific inflammation. Coagulation markers were not significantly different between clusters. Serum surrogates on cardiomyopathy and neuronal pathology exhibited significant variability. Implementation of ECMO or noninvasive ventilation was more prominent in cluster C and D. Interestingly, SOFA or APACHE II scores were not different between nominal (A and B) versus dysregulated clusters (C and D).

Background/Objectives: Interstitial lung disease (ILD) occurs commonly in systemic sclerosis (SSc) and is the leading cause of mortality. There are limited data on the accuracy of lung auscultation in identifying the presence of ILD in patients with SSc. Methods: We retrospectively identified patients with newly diagnosed SSc who had documented lung auscultation findings and chest high-resolution computed tomography (HRCT) available for review. Diagnoses were made by rheumatologists at Mayo Clinic, Rochester, Minnesota, USA over a 4-year period. Pulmonary function measurements included lung volumes, spirometry, and single-breath diffusing capacity. Results: Among 151 patients with SSc (median age, 62 years), 72.2% were female and 55.0% were never smokers. Limited cutaneous SSc was the most common phenotype (67.3%). Seventy (46.4%) patients were evaluated by pulmonologists. There was evidence of ILD by HRCT in 69 patients (45.7%); the most common pattern of ILD was fibrotic nonspecific interstitial pneumonia (59.2%). Respiratory symptoms were present in 46.4% of those with ILD compared to 15.9% among those without. The sensitivity and specificity for crackles heard by rheumatologists in detecting ILD were 50.7% and 97.6%, respectively; for pulmonologists, 71.4% and 85.7%, respectively. Presence of crackles was associated with high positive predictive values (94.6% for rheumatologists vs. 92.1% for pulmonologists, respectively); negative predictive values were moderate (70.2% vs. 56.3%, respectively). Crackles correlated with lower pulmonary function measures but did not differ across ILD patterns. Conclusions: Detection of crackles on lung auscultation appears to be a specific and moderately sensitive indicator of ILD (often asymptomatic) in patients with newly diagnosed SSc. The presence of crackles correlates with worse pulmonary function but may be absent in early ILD.

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 (t_adm), 48 h later (t_48h), and 7 days later (t_7d) 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 t_adm in smokers vs. nonsmokers (p = 0.0397). IgM at t_48h 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 t_adm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t_48h (CCL20↓, TRAIL↓) and t_7d (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.