Supplementary Table 3. Current studies investigating COVID-19/other coronavirus strains and TNF blockers. (continued).

Study Ref	Title	Authors	Country of study	Year	Summary of results
[36]	TNF-alpha inhibition for potential therapeutic modulation of SARS coronavirus infection.	Tobinick E.	US	2004	Clinical and experimental evidence implicate TNF as a possible mediator of the severe immune-based pulmonary injury which can follow infection with H5N1 influenza and SARS coronavirus. In humans, anti-TNF therapy utilising etanercept has been reported to be beneficial for treatment of the non-infectious idiopathic pneumonia syndrome which can follow stem-cell transplantation, a pulmonary syndrome that resembles SARS pneumonia in some respect. If the SARS coronavirus does indeed lead to massive release of TNF-αf rom alveolar macrophages, then early inhibition of TNF-α might be able to prevent TNF-αmediated immune activation and therefore reduce pulmonary injury in these patients. Compared with the use of corticosteroids, the use of biologic TNF inhibitors, including etanercept, has the potential to be a more specific and more effective method of ameliorating the severe alveolar damage which can occur following infection with these agents.
[37]	Anti-TNF alpha therapy does not ameliorate disease in a model of acute virus-endotoxin mediated respiratory disease in pigs.	Atanasova K; Van Gucht S; Van Reeth K.	Netherlands	2010	22 piglets were assessed to to elucidate the role of TNF-α in the development of virus-endotoxin-induced respiratory disease. The study demonstrates that after intratracheal administration etanercept is able to successfully block TNF-α activity in vivo in the lungs of PRCV-LPS inoculated pigs during the first 4–8 HPI. TNF-α reduction, however, was not associated with decrease in disease severity, bronchoalveolar neutrophil infiltration, or altered virus replication and induction of IL-1, IL-6, IL-12/IL-23 or IFN-α in the lungs. There was no obvious difference in macroscopic lung lesions and histopathological findings in the lungs. This data confirms the generally accepted belief that TNF-α, though very important, is not the sole culprit in development of respiratory disease and pathology, and possibly other, yet unidentified, components and mechanisms of the immune system are involved.