ABSTRACT
Introduction: SARS-CoV-2 infection has profound effects on endothelial and immune cell function and coagulation, and better understanding of these events in COVID-19 would allow for targeted cardiovascular treatment and followup. Method(s): Longitudinal observational study of patients with PCR-confirmed SARS-CoV-2 infection admitted to hospital at two UK sites. Patients were enrolled within 96 hours of admission, with sampling up to day 29. RNAstabilised whole blood was processed for mRNA sequencing. Gene expression levels were compared between patients who did and did not suffer a major cardiac event (MACE) from admission to 1-year post-hospitalization. Result(s): At day 1, in acute COVID-19, no differences in gene expression were observed between those with (n=23) and without (n=140) a MACE. However, 93 significant differentially expressed genes (DEGs;adjusted pvalue<0.05;Wald test with Benjamini-Hochberg correction) were identified at day 29 between patients who suffered a MACE (n=16) or not (n=85) post-hospitalization. Neutrophil elastase (ELANE), tissue factor pathways inhibitor (TFPI) and integrin subunit alpha-2 (ITGA2B) were significantly elevated in patients who suffered a MACE. Significantly enriched pathways associated with cardiovascular events included type I interferon signalling and neutrophil chemotaxis. Conclusion(s): COVID-19 patients who experienced a MACE demonstrated significant changes in peripheral blood transcriptome 29 days after hospital admission. Significant DEGs were related to neutrophil activity, coagulation and interferon signalling, suggesting a relationship between these pathways and increased cardiovascular risk.
ABSTRACT
IntroductionCOVID-19 has been reported to induce a ‘cytokine storm’ distinct from other acute respiratory tract infections (LRTIs). Understanding the similarities and differences in inflammatory profiles between SARS-CoV-2 infection and other respiratory infections may aid diagnosis, as well as the potential to repurpose therapies such as steroids and anti-IL-6 receptor antagonists for other respiratory infections.MethodsA prospective observational study of patients in 3 groups 1) PCR confirmed SARS-CoV-2 infection, 2) community-acquired pneumonia (CAP) without SARS-CoV-2, and 3) controls hospitalized for reasons other than infection. Patients were enrolled from a single centre in Dundee, UK. Patients were enrolled within 96 hours of hospital admission. 45 inflammatory biomarkers were measured in blood using the Olink target proteomic based biomarker panel. Additional markers were measured by ELISA/immunoassay and enzyme activity assay as appropriate. Discrimination between groups was evaluated using the area under the receiver operator characteristic curve (AUC).Results294 patients were included (COVID-19 n=176, CAP n=76, controls n=42), mean age 64 (SD±15.2) and 150 subjects were male (51.0%). Using ROC analysis the most discriminating biomarkers for COVID-19 compared to CAP were CXCL-10 (AUC 0.84 95%CI 0.78–0.90 p<0.001), CCL-8 (0.87 95%CI 0.82–0.92, p<0.001), CCL-7 (0.84 95%CI 0.78–0.89, p<0.001), CXCL-11 (0.80 95%CI 0.73–0.88, p<0.001). Further biomarkers included IL-18, IL-7, IL-10 and IL-33. The most discriminating biomarkers for COVID-19 compared to controls were CXCL-10 (0.89 95%CI 0.85–0.93, p<0.001, CCL-7 (0.88 95%CI 0.83–0.92, p<0.001), CCL-8 (0.87 95%CI 0.82–0.92, p<0.001). Further biomarkers included IL-10, CXCL-11 and IL-18. IL-4 was significantly lower in COVID-19 patients compared to controls (0.27 95%CI 0.16–0.38, p<0.001). No significant difference in IL-6 was seen between COVID-19 and CAP (median 21.9pg/ml vs 19.8pg/ml,p=0.59).ConclusionDifferential markers of inflammation were identified between COVID-19, CAP and control samples, indicating distinct immunological pathways. The identification of a similar IL-6 signature between COVID-19 and CAP indicates that IL-6 targeting therapies currently being used to treat COIVD-19 may also be beneficial in the treatment of CAP.