Hypersensitivity May Be Involved in Severe COVID-19

Deaths attributed to Coronavirus Disease 2019 (COVID-19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered main pathogenesis of severe COVID-19, hypersensitivity may be another important mechanism involved in severe cases, which have perfect response to corticosteroids (CS). We detected the presence of anti-SARS-CoV-2–spike S1 protein specific IgE (SP- IgE)and SARS-CoV-2 nucleocapsid protein specific IgE (NP- IgE)in all COVID-19 patients’ serum, while it was rarely detected in healthy controls. Additionally, the levels of serum SP- IgE and NP- IgE were significantly higher in severe cases, and which were correlations with the total lung severity scores (TLSS) and the PaO 2 /PAO 2 ratio. In both airway and intestinal tissues obtained from severe COVID-patients via endoscopy, NP could be stained and detected in activated mast cells, which binded with IgE. After application of CS in severe COVID-19, SP- IgE and NP- IgE decreased, but maintained at high level in early convalescence, which were maybe reason of airway hyperresponsiveness (AHR) in these patients partly. Overall, our study revealed that the chief mechanism of severe COVID-19–related hypoxemic respiratory failure is likely hypersensitivity reactions directly involving SARS-CoV-2 antigens, anti-SARS-CoV-2–specific IgE, and mast cells. Moreover, in our cohort of COVID-19 patients, severe COVID-19 patients with increased SP- IgE and NP-IgE and hypoxemic respiratory failure were treated with pulse methylprednisolone and achieved an excellent response. In conclusion, hypersensitivity may be involved in severe COVID-19. Funding Information: Guangdong Basic and Applied Basic Research Foundation (2020A1515011147) Zhuhai Science and Technology Project (ZH22036302200021PWC). Declaration of Interests: The authors of this manuscript declare no relationships with any companies whose products or services might be related to the subject matter of the article. Ethics Approval Statement: Our study was approved by the Research Ethics Committee of the Fifth Affiliated Hospital of Sun Yat-sen University. Written informed consent was obtained from all participants.