Nasopharyngeal inflammatory lymphocytes perturbation in COVID-19 severity prediction

Abstract

Abstract SARS-CoV-2 causes severe respiratory infections in some patients due to an uncontrolled immune response. The nasal microenvironment plays a crucial role in the transmission, modulation, and clinical progression of COVID-19, however, the immune-responses at the site of viral entry remain poorly understood. We used flow cytometry to decipher nasopharyngeal immune profiling of COVID-19 positive/negative patients; viral detection and load were performed by RT-PCR. Analysis of viral-induced immune-inflammatory responses, lymphocytes population/activation lymphocytes markers, T cell subtypes and associated inflammatory cytokines. Furthermore, we performed in vitro assays using cultured monocytes-derived-macrophages trained with/without SARS-CoV-2 spike protein and co-cultured with/without autologous T cells. Results showed that positive patients had high inflammatory CD45+ and CD8+ T cells including elevated % of Th1/Th17.1, associated with a worse outcome in a subgroup of COVID-19 infected patients. Positive patients showed increased % of cytokines, IFN-γ+, IL-17+, and IL-10+ T cells suggesting a crucial role of these cytokines in recruiting and activating neutrophils that can migrate to target organs (e.g., lungs) and potentially play an important role in the disease severity. Moreover, upregulated Tregs along with monocytic-induced inflammatory T-cell responses and increased TH1/TH17 cytokines in positive patients as compared to negative, potentially having a nefarious effect on disease progression. Our findings indicate a distinct signature of inflammatory lymphocytes/cytokines responses within the nasopharynx of COVID-19 patients that might predict the clinical outcome/progression of the disease. This work is supported by Dr. Mohamad Ayass, CEO of Ayass Bioscience, LLC