{"id":5878,"date":"2021-08-21T09:32:28","date_gmt":"2021-08-21T00:32:28","guid":{"rendered":"https:\/\/www.emukk.com\/WP\/?p=5878"},"modified":"2021-08-22T08:23:42","modified_gmt":"2021-08-21T23:23:42","slug":"severe-covid-19-originates-in-pyroptosis-as-many-as-10-of-circulating-monocytes-and-8-of-lung-macrophages-in-covid-19-patients-were-infected-with-sars-cov-2","status":"publish","type":"post","link":"https:\/\/www.emukk.com\/WP\/en\/severe-covid-19-originates-in-pyroptosis-as-many-as-10-of-circulating-monocytes-and-8-of-lung-macrophages-in-covid-19-patients-were-infected-with-sars-cov-2\/","title":{"rendered":"Severe COVID-19 originates in Pyroptosis: as many as 10% of circulating monocytes and 8% of lung macrophages in COVID-19 patients were infected with SARS-CoV-2"},"content":{"rendered":"

A group from Harvard Medical School, USA, etc. has reported that as many as 10% of circulating monocytes and 8% of lung macrophages in COVID-19 patients were infected with SARS-CoV-2, and FcR-mediated uptake of antibody-bound virus triggers inflammatory death (pyroptosis), which is really a double-edged sword in COVID-19.
\nhttps:\/\/www.researchsquare.com\/article\/rs-153628\/v1<\/a><\/p>\n

How SARS-CoV-2 triggers inflammation is not clearly understood. <\/p>\n

Monocytes and macrophages are sentinel immune cells in the blood and tissue, respectively. These immune cells sense invasive infection, and form inflammasomes that activate caspase-1 and gasdermin D (GSDMD) pores leading to pyroptosis and release of inflammatory cytokines. <\/p>\n

Monocytes are generally thought not to express ACE-2. Indeed, ACE-2 was not detected or barely detected by flow cytometry and qRT-PCR on both healthy donor (HD) monocytes, even when they were activated by SARS-CoV-2. Monocytes express 2 Fcg receptors \u2013 CD32 (FcgRII, expressed on most blood monocytes) and CD16 (FcgRIII, expressed on a small minority of blood monocytes that are activated and increased in number in COVID-19 patients). These receptors could recognize antibody-opsonized viral particles and mediate their entry via antibodydependent phagocytosis (ADP).
\nRelease of large proteins such as the tetramer LDH, is a pathognomonic feature of pyroptosis and other forms of necrotic cell death. Elevated LDH was one of the best correlates of severe COVID-19 disease. Plasma levels of GSDMD, LDH, IL-1RA and IL-18, were all elevated in severe patient samples compared to those with mild or moderate disease. And also, GSDMD eQTLs were most significantly associated with increased COVID-19 respiratory failure.<\/p>\n

\"\"<\/a><\/p>\n

After virus uptake, SARS-CoV-2 begins to replicate in monocytes, as evidenced by detection of double-stranded RNA etc. However, infection is aborted, and infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of the NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages from COVID-19 lung autopsy specimens showed similar evidence of inflammasome activation. These findings taken together suggest that antibody-mediated SARS-CoV-2 infection of monocytes\/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to severe COVID-19 disease pathogenesis. <\/p>\n","protected":false},"excerpt":{"rendered":"

A group from Harvard Medical School, USA, etc. has reported that as many as 10% of circulating monocytes and 8<\/p><\/div>\n

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