Defining Potential Therapeutic Targets in Coronavirus Disease 2019: A Cross-Sectional Analysis of a Single-Center Cohort

• Published in: Critical care explorations 2021-08, Vol.3 (8), p.e0488-e0488
• Main Authors: Arulkumaran, Nishkantha, Snow, Timothy Arthur Chandos, Kulkarni, Adarsh, Brealey, David, Rickman, Hannah, Rees-Spear, Chloe, Spyer, Moira J., Heaney, Judith, Garr, Edmund, Williams, Bryan, Cherepanov, Peter, Kassiotis, George, Lunn, Michael, Houlihan, Catherine, McCoy, Laura E., Nastouli, Eleni, Singer, Mervyn
• Format: Article
• Language: English
• Subjects: Observational Study
• ISSN: 2639-8028; 2639-8028
• DOI: 10.1097/CCE.0000000000000488

OBJECTIVESMultiple mechanisms have been proposed to explain disease severity in coronavirus disease 2019. Therapeutic approaches need to be underpinned by sound biological rationale. We evaluated whether serum levels of a range of proposed coronavirus disease 2019 therapeutic targets discriminated between patients with mild or severe disease. DESIGNA search of ClinicalTrials.gov identified coronavirus disease 2019 immunological drug targets. We subsequently conducted a retrospective observational cohort study investigating the association of serum biomarkers within the first 5 days of hospital admission relating to putative therapeutic biomarkers with illness severity and outcome. SETTINGUniversity College London, a tertiary academic medical center in the United Kingdom. PATIENTSPatients admitted to hospital with a diagnosis of coronavirus disease 2019. INTERVENTIONSNone. MEASUREMENTS AND MAIN RESULTSEighty-six patients were recruited, 44 (51%) with mild disease and 42 (49%) with severe disease. We measured levels of 10 cytokines/signaling proteins related to the most common therapeutic targets (granulocyte-macrophage colony-stimulating factor, interferon-α2a, interferon-β, interferon-γ, interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, interleukin-7, interleukin-8, tumor necrosis factor-α), immunoglobulin G antibodies directed against either coronavirus disease 2019 spike protein or nucleocapsid protein, and neutralization titers of antibodies. Four-hundred seventy-seven randomized trials, including 168 different therapies against 83 different pathways, were identified. Six of the 10 markers (interleukin-6, interleukin-7, interleukin-8, interferon-α2a, interferon-β, interleukin-1 receptor antagonist) discriminated between patients with mild and severe disease, although most were similar or only modestly raised above that seen in healthy volunteers. A similar proportion of patients with mild or severe disease had detectable spike protein or nucleocapsid protein immunoglobulin G antibodies with equivalent levels between groups. Neutralization titers were higher among patients with severe disease. CONCLUSIONSSome therapeutic and prognostic biomarkers may be useful in identifying coronavirus disease 2019 patients who may benefit from specific immunomodulatory therapies, particularly interleukin-6. However, biomarker absolute values often did not discriminate between patients with mild and severe disease or death, implying that these immunomodu