ESPE Yearbook of Paediatric Endocrinology

Hosp Pediatr. 2021 Jan;11(1):71–78. 10.1542/hpeds.2020-001917. https://pubmed.ncbi.nlm.nih.gov/33033078/

In a cohort of 82 children (0–21 years) who were hospitalised for severe SARS-CoV-2 associated respiratory illness, obesity was the strongest risk factor for the outcome of critical care. Already during the first COVID-19 wave, it was shown that obesity is a major risk factor for severe COVID-19 infection in adults and caused the age at disease manifestation to shift towards younger ages (1). Recent findings give insights into the underlying mechanism that links obesity to severe COVID-19 infection:

1. Obesity leads to respiratory dysfunction, characterised by increased airway resistance, reduced gas exchange and lung volume and muscle strength, and decreased diaphragmatic excursions (2,3). Transdifferentiation of pulmonary lipofibroblasts into myofibroblasts may contribute to the development of pulmonary fibrosis and thus aggravate the severity of COVID-19 associated lung disease (4).2. Insulin resistance and chronic subclinical inflammation associated with obesity lead to an increased vulnerability to infection-related lung failure (2).3. The expression of angiotensin converting enzyme 2 (the functional receptor of SARS-CoV-2) is upregulated in adipocytes from patients with obesity, making adipose tissue a potential target organ and viral reservoir (4).4. Leptin links metabolism to the immune response by signaling via the Jak/STATand Akt pathways. Increased circulating leptin levels seen in obesity lead to compromised systemic immune response. Leptin is also an important mediator of pulmonary immunity and elevated leptin levels worsen the pulmonary defense against infection (5). Leptin may also increase systemic inflammation via paracrine effects on T cells (6). In a mouse model, administration of antileptin antibody decreased pro-inflammatory events and improved lung pathology and survival (7).

Based on clinical observations and pathophysiological findings, specific recommendations for prevention and care of patients with obesity and COVID-19 disease have recently been published (8,9,10,11).

References: 1. Kass DA, Duggal P, Cingolani O. Obesity could shift severe COVID-19 disease to younger ages. Lancet 2020 May 16;395(10236):1544-1545. doi: 10.1016/S0140-6736(20)31024-2.2. Stefan N, Birkenfeld AL, Schulze MB, Ludwig DS. Obesity and Impaired Metabolic Health in Patients With COVID-19. Nat Rev Endocrinol. 2020;16(7):341-342. doi: 10.1038/s41574-020-0364-6.3. Dietz W, Santos-Burgoa C. Obesity and its implications for COVID-19 mortality. Obesity (Silver Spring). 2020; 28(6):1005. doi: 10.1002/oby.22818.4. Kruglikov IL, Scherer PE. The Role of Adipocytes and Adipocyte-Like Cells in the Severity of COVID-19 Infections. Obesity (Silver Spring) 2020 Jul;28(7):1187-1190. doi: 10.1002/oby.22856.5. Rebello CJ, Kirwan JP, Greenway FL. Obesity, the most common comorbidity in SARS-CoV-2: is leptin the link? Int J Obes (Lond) 2020 Sep;44(9):1810-1817. doi: 10.1038/s41366-020-0640-5.6. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol 2013;31:259-83. doi: 10.1146/annurev-immunol-032712-095956.7. Zhang AJX, et al. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. J Infect Dis 2013 Apr 15;207(8):1270-80. doi: 10.1093/infdis/jit031.8. Chiappetta S, Sharma AM, Bottino V, Stier C. COVID-19 and the role of chronic inflammation in patients with obesity. Int J Obes (Lond) 2020 Aug;44(8):1790-1792. doi: 10.1038/s41366-020-0597-4.9. Stavridou A, et al. Obesity in Children and Adolescents during COVID-19 Pandemic. Children (Basel) 2021 Feb 12;8(2):135. doi: 10.3390/children8020135.10. Pietrobelli A, et al. Effects of COVID-19 Lockdown on Lifestyle Behaviors in Children with Obesity Living in Verona, Italy: A Longitudinal Study. Obesity (Silver Spring) 2020 Aug;28(8):1382-1385.11. De Groot CJ, et al. Clinical management of patients with genetic obesity during COVID-19 pandemic: position paper of the ESE Growth & Genetic Obesity COVID-19 Study Group and Rare Endo-ERN main thematic group on Growth and Obesity. Endocrine 2021 Mar;71(3):653-662. doi: 10.1007/s12020-021-02619-y.