Th173 - The Underlying Mechanisms of Obesity-related COVID-19 Exacerbations

Tadashi Hosoya, PhD – Department of Rheumatology – Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Yoji Komiya, MD – Department of Rheumatology – Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Kawata Daisuke, MD – Department of Rheumatology – Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Mari Kamiya, PhD – Department of Rheumatology – Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Hideyuki Iwai, PhD – Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Sho Miyamoto – Department of Pathology – National Institute of Infectious Diseases; Takayuki Kanno – Department of Pathology – National Institute of Infectious Diseases; Minoru Tobiume – Department of Pathology – National Institute of Infectious Diseases; Akira Ainai, PhD – Department of Pathology, – National Institute of Infectious Diseases; Tadaki Suzuki – Department of Pathology – National Institute of Infectious Diseases; Hideki Hasegawa, PhD – Center for Influenza and Respiratory Virus Research – National Institute of Infectious Diseases; Shinsuke Yasuda, PhD – Professor, Department of Rheumatology, Tokyo Medical and Dental University

Abstract Text: Obesity has been recognized as one of the most significant risk factors for the deterioration and mortality associated with COVID-19. A certain proportion of COVID-19 patients experience marked elevations of inflammatory mediators termed “cytokine storm”, resulting in the deterioration of the respiratory condition. In the present study, we elucidated that the burden of high visceral adipose tissue (VAT) was more closely related to accelerated inflammatory responses and the mortality of Japanese COVID-19 patients than other obesity-associated markers, including body mass index and the burden of subcutaneous adipose tissue. After evaluating three different types of obese mice, we revealed that two C57BL/6 background obese mice, ob/ob mice and diet-induced obesity mice were extremely more vulnerable to mouse-adapted SARS-CoV-2 infection when compared to non-obese wild-type mice or even to similar obese db/db mice with slightly different genetic background. SARS-CoV-2 genome and proteins were more abundant in the lungs of ob/ob mice, engulfed in macrophages, resulting in increased production of inflammatory cytokine represented by IL-6. Both an anti-IL-6 receptor antibody treatment and the prevention of obesity by leptin replenishment improved the survival of SARS-CoV-2 infected ob/ob mice by reducing the viral protein burden and excessive immune responses. Our results have proposed that the VAT dominant obesity would be prone to cytokine storm due to SARS-CoV-2 infection and that anti-cytokine strategies can provide more beneficial effects to COVID-19 patients with this type of obesity, at least in Japanese patients.