Work

Female sex hormone, progesterone, ameliorates the severity of SARS-CoV-2-caused pneumonia in the Syrian hamster model

Year: 2022

Type: article

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 260 million people worldwide and causes coronavirus disease 2019 (COVID-19) with clinical spectrum ranging from mild to severe pneumonia. Recent clinical trials and experimental animal studies demonstrated that the severity of COVID-19 is lower in the females than in males. 1 However, it is unclear whether sex hormones are associated with disease severity in COVID-19 patients. Previously, the anti-inflammatory effects of progesterone, a major female sex hormone, were observed in patients who suffered from the influenza virus-infected diseases. 2 , 3 In this study, we aimed to investigate the role of progesterone in the Syrian hamster model of SARS-CoV-2 infection-caused lung pathogenesis. In order to model the male COVID-19 patients with severe pneumonia, male hamsters were intranasally infected with 1 × 10 4 plaque-forming unit (PFU) of SARS-CoV-2 (Fig. 1a ). The SARS-CoV-2-infected hamsters were untreated or treated with 1-, 3- or 5-dose of progesterone (1 mg/kg per dose) via intraperitoneal injection (Fig. 1a ). All of the hamsters with or without progesterone therapy survived throughout the infection course. The SARS-CoV-2-infected hamsters without progesterone treatment exhibited progressive body weight loss of up to 12.6 ± 1.1% from 1 to 7 days post infection (dpi) (Fig. 1b ). However, the SARS-CoV-2-infected hamsters treated with 1-, 3- or 5-dose of progesterone exhibited body weight loss of 9.6 ± 0.9%, 6.7 ± 1.1% or 5.1 ± 1.2% at 7 dpi, respectively (Fig. 1b ). The uninfected hamsters with or without 5-dose of progesterone treatment showed a body weight increase from 0 to 7 dpi (Fig. 1b ). These data suggested that progesterone rescued the body weight loss of the SARS-CoV-2-infected hamsters in a dose-dependent manner. Fig. 1 Detection of body weight, lung pathological changes and mRNA levels of proinflammatory cytokines in SARS-CoV-2 infected hamsters with or without progesterone treatment. a Schematic diagram of SARS-CoV-2 infection and animal operations. Hamsters were intranasally inoculated with 1 × 10 4 PFU of SARS-CoV-2, then received intraperitoneal injection of 1-, 3- or 5-dose of progesterone, respectively. Body weight were daily observed. Animals were euthanized at 7 dpi for virological and histological analysis. The SARS-CoV-2 infected hamsters without progesterone treatment (Untreated) were set as positive control group. The hamsters without SARS-CoV-2 infection and the hamsters with 5-dose of progesterone treatment were set as negative control groups. b Body weight changes of hamsters from 0 to 7 dpi ( n = 6). c Representative H&E staining for lung lobe sections collected from SARS-CoV-2 infected hamsters at 7 dpi (Bar = 200 μm). Comprehensive views of H&E staining were shown in Supplementary Fig. S1 . d Comprehensive pathological scores for lung sections were determined based on the severity and percentage of injured areas for each lung lobe. e Fold changes for mRNA levels of proinflammatory cytokines include IL-6, IL-10, TNF-α, and IFN-γ in the lung tissues collected from SARS-CoV-2 infected hamsters with 5-dose progesterone treatment at 7 dpi ( n = 6). The SARS-CoV-2 infected hamsters without treatment (Untreated) and the hamsters without SARS-CoV-2 infection (Mock) were set as control groups ( n = 6). The mRNA levels of proinflammatory cytokines were standardized to the house-keeping gene γ-actin Full size image

Source: Signal Transduction and Targeted Therapy

DOI: 10.1038/s41392-021-00860-5