The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide. As of2024, the SARS-CoV-2 Omicron variant is the predominant strain circulating within thepopulation, generally causing mild upper respiratory tract infections. However,hospitalizations and case fatalities due to COVID-19 continue, and there is a highprobability that a new human coronavirus will emerge in the future. Understanding thepathophysiology of severe COVID-19 remains highly relevant, as its mechanisms may becomparable to those of other respiratory viral infections.SARS-CoV-2 infects human cells primarily by binding to angiotensin-converting enzyme 2(ACE2) and type 2 transmembrane serine protease (TMPRSS2) receptors, which are bothexpressed in alveolar epithelial type II cells, through the virus' spike protein. In alater stage, the replication of SARS-CoV-2 and activation of resident immune cells leadto the infiltration and activation of large numbers of innate immune cells. Consequently,this results in an excessive pro-inflammatory immune response, including increasedproduction of IL-6, a hallmark cytokine of severe COVID-19. Eventually, the excessiveinflammation results in microthrombus formation and pulmonary edema.Further studies have indicated that SARS-CoV-2 spike-specific antibodies, along withalveolar macrophages, play a pivotal role in the pathophysiology of severe COVID-19.Alveolar macrophages, which reside in the lung alveoli, are typically the first immunecells to sense pulmonary pathogens. However, these cells can also bind IgG antibodiesthrough their Fc-receptor, leading to cellular activation. When stimulated with both aviral stimulus and anti-SARS-CoV-2 IgG antibodies from severe COVID-19 patients (asituation similar to that in the lungs of these patients) alveolar macrophages elicit asignificant proinflammatory response. This response aligns with the observed post-seralconversion deterioration in COVID-19 patients.Obesity is a significant risk factor for developing severe COVID-19, but the underlyingmechanism is not well understood. Previous studies report that macrophages in obesepatients are skewed towards a pro-inflammatory phenotype due to altered fatty acidcontents, particularly increased saturated fatty acids. Using our in vitro obesity model,which incorporates higher saturated fatty acid contents, the investigators alreadydemonstrated that SARS-CoV-2 antibody-mediated inflammation of alveolar macrophages isincreased (unpublished data). Thus, this may explain why obese patients are more likelyto develop severe COVID-19.To validate these in vitro findings, the investigators aim to confirm these results inmonocyte-derived macrophages isolated from individuals with and without obesity.Additionally, the investigators will investigate the underlying mechanisms involved indetail. This study will provide valuable insights into the role of obesity in severeCOVID-19 and potentially inform therapeutic strategies for at-risk populations.