tetano
Editor, Senior Moderator
Immunobiology
. 2023 Feb 15;228(2):152351.
doi: 10.1016/j.imbio.2023.152351. Online ahead of print.
Targeted genotyping of COVID-19 patients reveals a signature of complement C3 and factor B coding SNPs associated with severe infection
Stefanos A Tsiftsoglou[SUP] 1 [/SUP], Eleni Gavriilaki[SUP] 2 [/SUP], Tasoula Touloumenidou[SUP] 3 [/SUP], Evaggelia-Evdoxia Koravou[SUP] 3 [/SUP], Maria Koutra[SUP] 3 [/SUP], Penelope Georgia Papayanni[SUP] 3 [/SUP], Vassiliki Karali[SUP] 4 [/SUP], Apostolia Papalexandri[SUP] 3 [/SUP], Christos Varelas[SUP] 3 [/SUP], Fani Chatzopoulou[SUP] 5 [/SUP], Maria Chatzidimitriou[SUP] 6 [/SUP], Dimitrios Chatzidimitriou[SUP] 5 [/SUP], Anastasia Veleni[SUP] 7 [/SUP], Evdoxia Rapti[SUP] 8 [/SUP], Ioannis Kioumis[SUP] 9 [/SUP], Evaggelos Kaimakamis[SUP] 10 [/SUP], Milly Bitzani[SUP] 10 [/SUP], Dimitrios T Boumpas[SUP] 4 [/SUP], Argyris Tsantes[SUP] 8 [/SUP], Damianos Sotiropoulos[SUP] 3 [/SUP], Anastasia Papadopoulou[SUP] 3 [/SUP], Ioanna Sakellari[SUP] 3 [/SUP], Styliani Kokoris[SUP] 8 [/SUP], Achilles Anagnostopoulos[SUP] 3 [/SUP]
Affiliations
Abstract
We have attempted to explore further the involvement of complement components in the host COVID-19 (Coronavirus disease-19) immune responses by targeted genotyping of COVID-19 adult patients and analysis for missense coding Single Nucleotide Polymorphisms (coding SNPs) of genes encoding Alternative pathway (AP) components. We have identified a small group of common coding SNPs in Survivors and Deceased individuals, present in either relatively similar frequencies (CFH and CFI SNPs) or with stark differences in their relative abundance (C3 and CFB SNPs). In addition, we have identified several sporadic, potentially protective, coding SNPs of C3, CFB, CFD, CFH, CFHR1 and CFI in Survivors. No coding SNPs were detected for CD46 and CD55. Our demographic analysis indicated that the C3 rs1047286 or rs2230199 coding SNPs were present in 60 % of all the Deceased patients (n = 25) (the rs2230199 in 67 % of all Deceased Males) and in 31 % of all the Survivors (n = 105, p = 0.012) (the rs2230199 in 25 % of all Survivor Males). When we analysed these two major study groups using the presence of the C3 rs1047286 or rs2230199 SNPs as potential biomarkers, we noticed the complete absence of the protective CFB rs12614 and rs641153 coding SNPs from Deceased Males compared to Females (p = 0.0023). We propose that in these individuals, C3 carrying the R102G and CFB lacking the R32W or the R32Q amino acid substitutions, may contribute to enhanced association dynamics of the C3bBb AP pre-convertase complex assembly, thus enabling the exploitation of the activation of the Complement Alternative pathway (AP) by SARS-CoV-2.
Keywords: Alternative pathway; C3; CFB; COVID-19; Coding SNPs; Complement; Host genomics; SARS-CoV-2.
. 2023 Feb 15;228(2):152351.
doi: 10.1016/j.imbio.2023.152351. Online ahead of print.
Targeted genotyping of COVID-19 patients reveals a signature of complement C3 and factor B coding SNPs associated with severe infection
Stefanos A Tsiftsoglou[SUP] 1 [/SUP], Eleni Gavriilaki[SUP] 2 [/SUP], Tasoula Touloumenidou[SUP] 3 [/SUP], Evaggelia-Evdoxia Koravou[SUP] 3 [/SUP], Maria Koutra[SUP] 3 [/SUP], Penelope Georgia Papayanni[SUP] 3 [/SUP], Vassiliki Karali[SUP] 4 [/SUP], Apostolia Papalexandri[SUP] 3 [/SUP], Christos Varelas[SUP] 3 [/SUP], Fani Chatzopoulou[SUP] 5 [/SUP], Maria Chatzidimitriou[SUP] 6 [/SUP], Dimitrios Chatzidimitriou[SUP] 5 [/SUP], Anastasia Veleni[SUP] 7 [/SUP], Evdoxia Rapti[SUP] 8 [/SUP], Ioannis Kioumis[SUP] 9 [/SUP], Evaggelos Kaimakamis[SUP] 10 [/SUP], Milly Bitzani[SUP] 10 [/SUP], Dimitrios T Boumpas[SUP] 4 [/SUP], Argyris Tsantes[SUP] 8 [/SUP], Damianos Sotiropoulos[SUP] 3 [/SUP], Anastasia Papadopoulou[SUP] 3 [/SUP], Ioanna Sakellari[SUP] 3 [/SUP], Styliani Kokoris[SUP] 8 [/SUP], Achilles Anagnostopoulos[SUP] 3 [/SUP]
Affiliations
- PMID: 36805858
- DOI: 10.1016/j.imbio.2023.152351
Abstract
We have attempted to explore further the involvement of complement components in the host COVID-19 (Coronavirus disease-19) immune responses by targeted genotyping of COVID-19 adult patients and analysis for missense coding Single Nucleotide Polymorphisms (coding SNPs) of genes encoding Alternative pathway (AP) components. We have identified a small group of common coding SNPs in Survivors and Deceased individuals, present in either relatively similar frequencies (CFH and CFI SNPs) or with stark differences in their relative abundance (C3 and CFB SNPs). In addition, we have identified several sporadic, potentially protective, coding SNPs of C3, CFB, CFD, CFH, CFHR1 and CFI in Survivors. No coding SNPs were detected for CD46 and CD55. Our demographic analysis indicated that the C3 rs1047286 or rs2230199 coding SNPs were present in 60 % of all the Deceased patients (n = 25) (the rs2230199 in 67 % of all Deceased Males) and in 31 % of all the Survivors (n = 105, p = 0.012) (the rs2230199 in 25 % of all Survivor Males). When we analysed these two major study groups using the presence of the C3 rs1047286 or rs2230199 SNPs as potential biomarkers, we noticed the complete absence of the protective CFB rs12614 and rs641153 coding SNPs from Deceased Males compared to Females (p = 0.0023). We propose that in these individuals, C3 carrying the R102G and CFB lacking the R32W or the R32Q amino acid substitutions, may contribute to enhanced association dynamics of the C3bBb AP pre-convertase complex assembly, thus enabling the exploitation of the activation of the Complement Alternative pathway (AP) by SARS-CoV-2.
Keywords: Alternative pathway; C3; CFB; COVID-19; Coding SNPs; Complement; Host genomics; SARS-CoV-2.