A deficient immune response to SARS-CoV-2 in the nasopharynx is associated with severe COVID-19 pneumonia.

OBJECTIVES: We analyzed the expression of inflammatory and antiviral genes in the nasopharynx of SARS-CoV-2 infected patients and their association with the severity of COVID-19 pneumonia. METHODS: We conducted a cross-sectional study on 223 SARS-CoV-2 infected patients. Clinical data were collected from medical records, and nasopharyngeal samples were collected in the first 24 hours after admission to the emergency room. The gene expression of eight proinflammatory/antiviral genes (plasminogen activator urokinase receptor [PLAUR], interleukin [IL]-6, IL-8, interferon [IFN]-ß, IFN-stimulated gene 15 [ISG15], retinoic acid-inducible gene I [RIG-I], C-C motif ligand 5 [CCL5], and chemokine C-X-C motif ligand 10 [CXCL10]) were quantified by real-time polymerase chain reaction. Outcome variables were: (i) pneumonia; (ii) severe pneumonia or acute respiratory distress syndrome. Statistical analysis was performed using multivariate logistic regression analyses. RESULTS: We enrolled 84 mild, 88 moderate, and 51 severe/critical cases. High expression of PLAUR (adjusted odds ratio [aOR] = 1.25; P = 0.032, risk factor) and low expression of CXCL10 (aOR = 0.89; P = 0.048, protective factor) were associated with pneumonia. Furthermore, lower values of ISG15 (aOR = 0.88, P = 0.021), RIG-I (aOR = 0.87, P = 0.034), CCL5 (aOR = 0.73, P <0.001), and CXCL10 (aOR = 0.84, P = 0.002) were risk factors for severe pneumonia/acute respiratory distress syndrome. CONCLUSION: An unbalanced early innate immune response to SARS-CoV-2 in the nasopharynx, characterized by high expression of PLAUR and low expression of antiviral genes (ISG15 and RIG-I), and chemokines (CCL5 and CXCL10), was associated with COVID-19 severity.

High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity.

Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2-infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among hospital workers in a severely affected institution in Madrid, Spain: A surveillance cross-sectional study.

OBJECTIVE: To analyze the impact of the coronavirus disease 2019 (COVID-19) pandemic in workers of a hospital located in one of the most affected areas in Spain. DESIGN, SETTINGS, AND PATIENTS: Cross-sectional study performed between March and May 2020 over all workers of a secondary hospital in Madrid, Spain. METHODS: We employed polymerase chain reaction (PCR, for symptomatic individuals) and serology (for both PCR-negative symptomatic workers and asymptomatic workers) as diagnostic tests for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We analyzed the prevalence of the virus in healthcare workers (HCWs) and nonhealthcare workers (nHCWs). We also collected information about the use of personal protective equipment (PPEs) and possible contacts prior to infection. RESULTS: In total, 2,963 workers were included: 1,092 were symptomatic, and of these, 539 were positive by PCR (49.4% of symptomatic workers). From the remaining symptomatic workers, 197 (35.6%) were positive by serology. Regarding asymptomatic workers, 345 were positive by serology (31.9% of infected workers). In total, 1,081 (36.5%) presented a positive diagnostic test for SARS-CoV-2. Infection rates were different between HCWs (37.4%) and nHCWs (29.8%) (P = .006). In the multivariate logistic regression analysis, the use of PPE (protective: OR, 0.56; 95% CI, 0.44-0.72; P < .001) and previous contact with COVID-19 patients (risk factor: OR, 1.69; 95% CI, 1.28-2.24; P < .001) were independent factors that were associated with SAS-CoV-2 infection. CONCLUSIONS: Overall, >36% of our workers became infected with SARS-CoV-2, and the rate of asymptomatic infections accounted for almost 32% of all SARS-CoV-2 infections. We detected differences in the rates of infection between HCWs and nHCWs. The use of PPE and previous contact with COVID-19 patients were associated with SARS-CoV-2 infection.