Supplementary Table 6. Current studies investigating COVID-19/ other coronavirus strains and IL-1 blockade.

Study Ref	Title	Authors	Country of study	Year	Summary of results
[62]	Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia.	Chen et al	China	2020	The levels of several inflammatory markers were measured in 29 COVID-19 patients and were compared between general, severe and critically ill groups. The authors reported no significant differences in IL-1b levels between the three groups of patients.
[63]	Rat coronaviruses infect rat alveolar type I epithelial cells and induce expression of CXC chemokines.	Miura et al	USA	2007	The authors used two rat coronaviruses on alveolar epithelial cells taken from 6-8 weeks old rats. Infection with the viruses caused the increase in expressed of both IL-1a and IL-1b. The authors concluded that the virus-induced chemokine expression was subsequently reduced by the IL-1 receptor antagonist, suggesting that IL-1 produced by infected cells induces uninfected cells to express chemokines.
[64]	Role of the inflammasome-related cytokines Il-1 and Il-18 during infection with murine coronavirus.	Zalinger, Elliott and Weiss	USA	2017	The authors used several infectious agents including murine coronavirus to assess the role of the inflammasome and its related cytokines on pathogenesis and host defence during viral infection. The authors concluded that mice lacking IL-1 signalling experienced elevated viral replication but similar survival compared to wild-type controls.
[65]	Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome.	Chen et al	Japan and Taiwan	2019	The authors provide evidence that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages and that the ion channel activity of the 3a protein was essential for 3a-mediated IL-1β secretion. The macrophages obtained in this study were from 6-week-old female mice.
[66]	Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy.	Kritas et al	Greece, Italy and USA	2020	(Abstract Only) Infection with coronavirus activates mast cells which in turn causes the generation of pro-inflammatory IL-1 family members. The authors state that they demonstrate for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family. However, as this is only an abstract there is no further information to support this statement.
[67]	SARS Immunity and Vaccination.	Zhu M	China	2004	SARS-CoV binds to host cells via a specific SARS receptor, angiotensin converting enzyme 2 (ACE-2). Following entry into the cell, the virus uncoats, nucleic acid is released and transcription occurs for production of viral proteins. During this course, the host immune system is activated (B and T-cells). Specifically, CD4+ T helper cells recognise antigenic peptides produced by antigen presenting cells and produce cytokines that promote cell mediated and/or humoral immunity. Similarly to avian flu, SARS infection induced similar pro-inflammatory cytokine pattern and might contribute to the severe nature of the virus. Clinical evidence of SARS treatment by corticosteroids where levels of IL-1beta reduced after administration- thus inhibition of inflammatory cytokines such as IL-1 may be beneficial strategy for treatment of SARS.
[54]	Analysis of serum cytokines in patients with severe acute respiratory syndrome.	Zhang Y, Li J, Zhan Y, Wu L, Yu X, Zhang W, Ye L, Xu S, Sun R, Wang Y, Lou J	China	2004	Following the discovery of SARS-CoV, no specific or efficient clinical treatments were available since pathogenesis was not well understood. Acute lung injury associated with SARS can be attributed to complex and multifactorial pathophysiological process involving cytokines. Demonstrated that IL-1 play key role in pathogenesis of acute lung injury. WHO inferred that severe immune response kills SARS patients and that some cytokines may play important role in the process. IL-1 cytokine promotes inflammation by inducing cell injury. Study measured levels of IL-1 in 4 patient groups: controls, patients with SARS, patients with severe SARS and convalescent SARS patients. Study showed that levels of IL-1alpha did not differ between 3 SARS groups or controls. Suggests that host immune response to novel coronavirus may be different from the immune reaction to other pathogens. Overall results suggest that acute lung injury associated with SARS may not be induced by circulating cytokines. HOWEVER some patients had accepted corticosteroids and therefore results consistent with reports that only long term treatment (7-10 days) with a steroid can alter serum cytokine levels.
[34]	Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome.	Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, Lit LC, Hui DS, Chan MH, Chung SS, Sung JJ	Hong Kong	2004	Known that over-expression of IL-1beta hallmark of SARS infection probably through activation of transcription factor nuclear factor, activator protein AP1 and activating factor 2. Therefore lung damage associated with SARS postulated to occur through cytokine and chemokine dysregulation. Study involved measurement of cytokines and chemokines including IL-1beta in 20 consecutive patients admitted to Hong Kong hospital. IL-1beta was significantly elevated above normal range within first 12, 7 and 5 days after disease onset. Those patients with more severe disease treated with pulsed methylprednisolone. IL-1beta levels higher in this patient group particularly 3-10 days after onset but returned to normal levels 1 week after disease onset in both sets of patients. IL-1beta can act as early response cytokine to viral infection. IL-1 elevation in SARS can induce hyperinnate inflammatory response leading to recruitment and accumulation of alveolar macrophages and PMN. Higher disease severity associated with more elevated plasma IL-1beta and addition of pulsed steroid controlled rapidly deteriorating clinical condition and attenuated otherwise exaggerated immunological response.