RGD Reference Report - Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection. - Rat Genome Database

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Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection.

Authors: Ramlall, Vijendra  Thangaraj, Phyllis M  Meydan, Cem  Foox, Jonathan  Butler, Daniel  Kim, Jacob  May, Ben  De Freitas, Jessica K  Glicksberg, Benjamin S  Mason, Christopher E  Tatonetti, Nicholas P  Shapira, Sagi D 
Citation: Ramlall V, etal., Nat Med. 2020 Aug 3. pii: 10.1038/s41591-020-1021-2. doi: 10.1038/s41591-020-1021-2.
RGD ID: 38500238
Pubmed: PMID:32747830   (View Abstract at PubMed)
PMCID: PMC7809634   (View Article at PubMed Central)
DOI: DOI:10.1038/s41591-020-1021-2   (Journal Full-text)

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral-host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality-effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
A2MHumanCOVID-19 severityIAGP DNA:SNPs: :RGD 
A2mRatCOVID-19 severityISOA2M (Homo sapiens)DNA:SNPs: :RGD 
A2mMouseCOVID-19 severityISOA2M (Homo sapiens)DNA:SNPs: :RGD 
C3RatCOVID-19 severityISOC3 (Homo sapiens)DNA:SNPs: :rs1047286 more ...RGD 
C3HumanCOVID-19 severityIAGP DNA:SNPs: :rs1047286 more ...RGD 
C3MouseCOVID-19 severityISOC3 (Homo sapiens)DNA:SNPs: :rs1047286 more ...RGD 
C4BPAHumanCOVID-19 severityIAGP DNA:SNP: :rs61821041(human)RGD 
C4BPBHumanCOVID-19 severityIAGP DNA:SNP: :rs45574833(human)RGD 
C4bpaRatCOVID-19 severityISOC4BPA (Homo sapiens)DNA:SNP: :rs61821041(human)RGD 
C4bpbRatCOVID-19 severityISOC4BPB (Homo sapiens)DNA:SNP: :rs45574833(human)RGD 
CFHHumanCOVID-19 severityIAGP DNA:SNP: :RGD 
CfhRatCOVID-19 severityISOCFH (Homo sapiens)DNA:SNP: :RGD 
CfhMouseCOVID-19 severityISOCFH (Homo sapiens)DNA:SNP: :RGD 
F3RatCOVID-19 severityISOF3 (Homo sapiens)DNA:SNP: : (rs72729504) (human)RGD 
F3HumanCOVID-19 severityIAGP DNA:SNP: : (rs72729504) (human)RGD 
F3MouseCOVID-19 severityISOF3 (Homo sapiens)DNA:SNP: : (rs72729504) (human)RGD 
SERPINF2HumanCOVID-19 severityIAGP DNA:SNP: :RGD 
SERPING1HumanCOVID-19 severityIAGP DNA:SNP: :RGD 
Serpinf2RatCOVID-19 severityISOSERPINF2 (Homo sapiens)DNA:SNP: :RGD 
Serpinf2MouseCOVID-19 severityISOSERPINF2 (Homo sapiens)DNA:SNP: :RGD 
Serping1RatCOVID-19 severityISOSERPING1 (Homo sapiens)DNA:SNP: :RGD 
Serping1MouseCOVID-19 severityISOSERPING1 (Homo sapiens)DNA:SNP: :RGD 
Zp3rMouseCOVID-19 severityISOC4BPA (Homo sapiens)DNA:SNP: :rs61821041(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
A2m  (alpha-2-macroglobulin)
C3  (complement C3)
C4bpa  (complement component 4 binding protein, alpha)
C4bpb  (complement component 4 binding protein, beta)
Cfh  (complement factor H)
F3  (coagulation factor III, tissue factor)
Serpinf2  (serpin family F member 2)
Serping1  (serpin family G member 1)

Genes (Mus musculus)
A2m  (alpha-2-macroglobulin)
C3  (complement component 3)
Cfh  (complement component factor h)
F3  (coagulation factor III)
Serpinf2  (serine (or cysteine) peptidase inhibitor, clade F, member 2)
Serping1  (serine (or cysteine) peptidase inhibitor, clade G, member 1)
Zp3r  (zona pellucida 3 receptor)

Genes (Homo sapiens)
A2M  (alpha-2-macroglobulin)
C3  (complement C3)
C4BPA  (complement component 4 binding protein alpha)
C4BPB  (complement component 4 binding protein beta)
CFH  (complement factor H)
F3  (coagulation factor III, tissue factor)
SERPINF2  (serpin family F member 2)
SERPING1  (serpin family G member 1)

Objects referenced in this article
Gene CD55 CD55 molecule (Cromer blood group) Homo sapiens
Gene Cd55 CD55 molecule, decay accelerating factor for complement Mus musculus
Gene Cd55 CD55 molecule (Cromer blood group) Rattus norvegicus

Additional Information