Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines. Issue 9 (22nd May 2020)

• Record Type: Journal Article
• Authors: Zheng, Yunfeng; Li, Renfeng; Liu, Shunai
• Other Names: Luo Guangxiang (George) guestEditor.; Ly Hinh guestEditor.; Gao Shou‐Jiang guestEditor.
• Is Part Of: Journal of medical virology. Volume 92:Issue 9(2020)
• Page Start: 1495
• Page End: 1500
• Publication Date: 2020-05-22
• Subjects: ADE -- antibody‐dependent enhancement -- coronavirus -- cross‐reactive antibody -- cytokine storm -- immunity -- mTOR inhibitors -- rapamycin; Virology -- Periodicals; 616
• DOI: 10.1002/jmv.26009
• Languages: English
• ISSNs: 0146-6615

Abstract

Abstract: Coronavirus disease 2019 (COVID‐19) has become a major global public health concern. The mortality rate for critically ill patients is up to 60%, and, thus, reducing the disease severity and case mortality is a top priority. Currently, cytokine storms are considered as the major cause of critical illness and death due to COVID‐19. After a systematical review of the literature, we propose that cross‐reactive antibodies associated with antibody‐dependent enhancement (ADE) may actually be the cause of cytokine storms. It would be more difficult to develop vaccines for highly pathogenic human coronaviruses (CoVs) if ADE characteristics are taken into consideration. Therefore, it is urgent to find an effective way to prevent the occurrence of severe illness as severe acute respiratory syndrome CoV‐2 specific drugs or vaccines are still in development. If the activation of memory B cells can be selectively inhibited in high‐risk patients at an early stage of COVID‐19 to reduce the production of cross‐reactive antibodies against the virus, we speculate that ADE can be circumvented and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such needs and it is recommended to conduct clinical trials for mTOR inhibitors in preventing the severity of COVID‐19. Highlights: Cytokine storms are the major cause of critical illness and death due to COVID‐19. Antibody‐dependent enhancement (ADE) may be the major cause of cytokine storms. Selective inhibition of memory B cell activation by mTOR inhibitors could prevent ADE and reduce COVID‐19 severity.