Obesity, ethnicity and risk of critical care, mechanical ventilation and mortality in patients admitted to hospital with COVID-19: Analysis of the ISARIC CCP-UK cohort.

Objective: The  aim  of  this  study  was  to  investigate  the  asso-ciation  of  obesity  with  in-  hospital  coronavirus  disease  2019  (COVID- 19) outcomes in different ethnic groups.Methods: Patients  admitted  to  hospital  with  COVID-  19  in  the  United  Kingdom  through  the  Clinical  Characterisation  Protocol  UK  (CCP-  UK)  developed  by  the  International  Severe  Acute  Respiratory and emerging Infections Consortium (ISARIC) were included  from  February  6  to  October  12,  2020.  Ethnicity  was  classified as White, South Asian, Black, and other minority eth-nic groups. Outcomes were admission to critical care, mechani-cal  ventilation,  and  in-  hospital  mortality,  adjusted  for  age,  sex,  and chronic diseases.Results: Of  the  participants  included,  54,254  (age  =  76  years;  45.0%  women)  were  White,  3,728  (57  years;  41.1%  women)  were South Asian, 2,523 (58 years; 44.9% women) were Black, and  5,427  (61  years;  40.8%  women)  were  other  ethnicities.  Obesity was associated with all outcomes in all ethnic groups, with associations strongest for black ethnicities. When stratified by ethnicity and obesity status, the odds ratios for admission to critical care, mechanical ventilation, and mortality in black eth-nicities with obesity were 3.91 (3.13- 4.88), 5.03 (3.94- 6.63), and 1.93  (1.49-  2.51),  respectively,  compared  with  White  ethnicities  without obesity.Conclusions: Obesity  was  associated  with  an  elevated  risk  of  in- hospital COVID- 19 outcomes in all ethnic groups, with asso-ciations strongest in Black ethnicities.</p

Accelarated immune ageing is associated with COVID-19 disease severity

Background: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (β = 0.174, p = 0.043), with a major influence being disease severity (β = 0.188, p = 0.01). Conclusions: Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease