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Posted On: 02/07/2021 3:38:53 PM
Post# of 148891
This should help you all sleep better.
Results and discussion.
The main finding of our study was a significantly lower frequency of CCR5-Δ32 among the COVID-19 patients (table 1). Multiple logistic regression with age, sex and hypertension showed that in our population carriers of the 32 bp deletion were significantly less frequent among the patients (30/294=0.10 vs 85/460=0.18 in controls; p=0.002, OR=0.48, 95%CI=0.29-0.76). The difference was mainly due to the reduced frequency of CCR5-Δ32 carriers in the severe-ICU group, significantly lower than in the non-severe patients (p=0.036). Of note, we did not find deletion-homozygotes among the patients compared to 1% among controls. Carriers of the deletion would express less membrane-bound receptor and an attenuated pro-inflammatory response mediated by the ligand binding to CCR5. This might explain the reported protective effect of Δ32 on the development of clinical manifestations with underlying inflammatory mechanisms, such as atherosclerosis and coronary heart disease (Muntinghe et al., 2009; González et al., 2001; Vangelista and Vento, 2018). In addition to the well-known protective effect against HIV-1, this variant has been investigated in reference to the clinical outcomes of several viral infections, such as hepatitis B and influenza A (Ruiz-Mateos et al., 2018; Ellwanger et al., 2020). Because CCR5 is not a recognised receptor for SARS-Cov-2 the most likely explanation for the protective effect of Δ32 in COVID-19 is an attenuated inflammatory response among the CCR5-deletion carriers. This finding was in agreement with a report that showed that mice lacking CCR5 infected with a neurotropic coronavirus showed an attenuated inflammatory response, with reduced macrophage infiltration and demyelination (Glass et al., 2001).
https://www.medrxiv.org/content/10.1101/2020....1.full.pdf
Results and discussion.
The main finding of our study was a significantly lower frequency of CCR5-Δ32 among the COVID-19 patients (table 1). Multiple logistic regression with age, sex and hypertension showed that in our population carriers of the 32 bp deletion were significantly less frequent among the patients (30/294=0.10 vs 85/460=0.18 in controls; p=0.002, OR=0.48, 95%CI=0.29-0.76). The difference was mainly due to the reduced frequency of CCR5-Δ32 carriers in the severe-ICU group, significantly lower than in the non-severe patients (p=0.036). Of note, we did not find deletion-homozygotes among the patients compared to 1% among controls. Carriers of the deletion would express less membrane-bound receptor and an attenuated pro-inflammatory response mediated by the ligand binding to CCR5. This might explain the reported protective effect of Δ32 on the development of clinical manifestations with underlying inflammatory mechanisms, such as atherosclerosis and coronary heart disease (Muntinghe et al., 2009; González et al., 2001; Vangelista and Vento, 2018). In addition to the well-known protective effect against HIV-1, this variant has been investigated in reference to the clinical outcomes of several viral infections, such as hepatitis B and influenza A (Ruiz-Mateos et al., 2018; Ellwanger et al., 2020). Because CCR5 is not a recognised receptor for SARS-Cov-2 the most likely explanation for the protective effect of Δ32 in COVID-19 is an attenuated inflammatory response among the CCR5-deletion carriers. This finding was in agreement with a report that showed that mice lacking CCR5 infected with a neurotropic coronavirus showed an attenuated inflammatory response, with reduced macrophage infiltration and demyelination (Glass et al., 2001).
https://www.medrxiv.org/content/10.1101/2020....1.full.pdf
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