AUTHOR=Choreño-Parra José Alberto , Jiménez-Álvarez Luis Armando , Cruz-Lagunas Alfredo , Rodríguez-Reyna Tatiana Sofía , Ramírez-Martínez Gustavo , Sandoval-Vega Montserrat , Hernández-García Diana Lizzeth , Choreño-Parra Eduardo M. , Balderas-Martínez Yalbi I. , Martinez-Sánchez Mariana Esther , Márquez-García Eduardo , Sciutto Edda , Moreno-Rodríguez José , Barreto-Rodríguez José Omar , Vázquez-Rojas Hazel , Centeno-Sáenz Gustavo Iván , Alvarado-Peña Néstor , Salinas-Lara Citlaltepetl , Sánchez-Garibay Carlos , Galeana-Cadena David , Hernández Gabriela , Mendoza-Milla Criselda , Domínguez Andrea , Granados Julio , Mena-Hernández Lula , Pérez-Buenfil Luis Ángel , Domínguez-Cheritt Guillermo , Cabello-Gutiérrez Carlos , Luna-Rivero Cesar , Salas-Hernández Jorge , Santillán-Doherty Patricio , Regalado Justino , Hernández-Martínez Angélica , Orozco Lorena , Ávila-Moreno Federico , García-Latorre Ethel A. , Hernández-Cárdenas Carmen M. , Khader Shabaana A. , Zlotnik Albert , Zúñiga Joaquín TITLE=Clinical and Immunological Factors That Distinguish COVID-19 From Pandemic Influenza A(H1N1) JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.593595 DOI=10.3389/fimmu.2021.593595 ISSN=1664-3224 ABSTRACT=

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.