Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study
- PMID: 33015645
- PMCID: PMC7524533
- DOI: 10.1016/S2665-9913(20)30343-X
Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study
Abstract
Background: A subset of patients with COVID-19 develops a hyperinflammatory syndrome that has similarities with other hyperinflammatory disorders. However, clinical criteria specifically to define COVID-19-associated hyperinflammatory syndrome (cHIS) have not been established. We aimed to develop and validate diagnostic criteria for cHIS in a cohort of inpatients with COVID-19.
Methods: We searched for clinical research articles published between Jan 1, 1990, and Aug 20, 2020, on features and diagnostic criteria for secondary haemophagocytic lymphohistiocytosis, macrophage activation syndrome, macrophage activation-like syndrome of sepsis, cytokine release syndrome, and COVID-19. We compared published clinical data for COVID-19 with clinical features of other hyperinflammatory or cytokine storm syndromes. Based on a framework of conserved clinical characteristics, we developed a six-criterion additive scale for cHIS: fever, macrophage activation (hyperferritinaemia), haematological dysfunction (neutrophil to lymphocyte ratio), hepatic injury (lactate dehydrogenase or asparate aminotransferase), coagulopathy (D-dimer), and cytokinaemia (C-reactive protein, interleukin-6, or triglycerides). We then validated the association of the cHIS scale with in-hospital mortality and need for mechanical ventilation in consecutive patients in the Intermountain Prospective Observational COVID-19 (IPOC) registry who were admitted to hospital with PCR-confirmed COVID-19. We used a multistate model to estimate the temporal implications of cHIS.
Findings: We included 299 patients admitted to hospital with COVID-19 between March 13 and May 5, 2020, in analyses. Unadjusted discrimination of the maximum daily cHIS score was 0·81 (95% CI 0·74-0·88) for in-hospital mortality and 0·92 (0·88-0·96) for mechanical ventilation; these results remained significant in multivariable analysis (odds ratio 1·6 [95% CI 1·2-2·1], p=0·0020, for mortality and 4·3 [3·0-6·0], p<0·0001, for mechanical ventilation). 161 (54%) of 299 patients met two or more cHIS criteria during their hospital admission; these patients had higher risk of mortality than patients with a score of less than 2 (24 [15%] of 138 vs one [1%] of 161) and for mechanical ventilation (73 [45%] vs three [2%]). In the multistate model, using daily cHIS score as a time-dependent variable, the cHIS hazard ratio for worsening from low to moderate oxygen requirement was 1·4 (95% CI 1·2-1·6), from moderate oxygen to high-flow oxygen 2·2 (1·1-4·4), and to mechanical ventilation 4·0 (1·9-8·2).
Interpretation: We proposed and validated criteria for hyperinflammation in COVID-19. This hyperinflammatory state, cHIS, is commonly associated with progression to mechanical ventilation and death. External validation is needed. The cHIS scale might be helpful in defining target populations for trials and immunomodulatory therapies.
Funding: Intermountain Research and Medical Foundation.
© 2020 Elsevier Ltd. All rights reserved.
Similar articles
-
Laboratory trends, hyperinflammation, and clinical outcomes for patients with a systemic rheumatic disease admitted to hospital for COVID-19: a retrospective, comparative cohort study.Lancet Rheumatol. 2021 Sep;3(9):e638-e647. doi: 10.1016/S2665-9913(21)00140-5. Epub 2021 May 28. Lancet Rheumatol. 2021. PMID: 34095857 Free PMC article.
-
Identifying COVID-19 Confirmed Patients at Elevated Risk for Mortality and Need of Mechanical Ventilation Using a Novel Criteria for Hyperinflammatory Syndrome: A Retrospective Cohort, Single-center, Validation Study.Acta Med Philipp. 2025 Feb 28;59(3):104-115. doi: 10.47895/amp.vi0.9370. eCollection 2025. Acta Med Philipp. 2025. PMID: 40151221 Free PMC article.
-
Assessment of Admission COVID-19 Associated Hyperinflammation Syndrome Score in Critically-Ill COVID-19 Patients.J Intensive Care Med. 2023 Jan;38(1):70-77. doi: 10.1177/08850666221131265. Epub 2022 Oct 10. J Intensive Care Med. 2023. PMID: 36213939 Free PMC article.
-
Drugs for paediatric hyperinflammatory syndromes.Drugs Context. 2022 May 27;11:2022-2-1. doi: 10.7573/dic.2022-2-1. eCollection 2022. Drugs Context. 2022. PMID: 35720057 Free PMC article. Review.
-
Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and hemophagocytic lymphohistiocytosis.Curr Opin Rheumatol. 2014 Sep;26(5):562-9. doi: 10.1097/BOR.0000000000000093. Curr Opin Rheumatol. 2014. PMID: 25022357 Free PMC article. Review.
Cited by
-
Could SARS-CoV-2 blocking of ACE2 in endothelial cells result in upregulation of CX3CL1, promoting thrombosis in COVID-19 patients?Med Hypotheses. 2021 Jun;151:110570. doi: 10.1016/j.mehy.2021.110570. Epub 2021 Mar 25. Med Hypotheses. 2021. PMID: 33836338 Free PMC article.
-
COVID-19 cytokine storm syndrome: a threshold concept.Lancet Microbe. 2021 Feb;2(2):e49-e50. doi: 10.1016/S2666-5247(20)30223-8. Epub 2021 Feb 2. Lancet Microbe. 2021. PMID: 33655230 Free PMC article. No abstract available.
-
Macrophage Activation Syndrome in Children: Update on Diagnosis and Treatment.Children (Basel). 2024 Jun 21;11(7):755. doi: 10.3390/children11070755. Children (Basel). 2024. PMID: 39062205 Free PMC article. Review.
-
A simple nomogram for predicting infectious diseases in adult kidney transplantation recipients.Front Public Health. 2022 Aug 31;10:944137. doi: 10.3389/fpubh.2022.944137. eCollection 2022. Front Public Health. 2022. PMID: 36117592 Free PMC article.
-
Downregulation of sCD40 and sCTLA4 in Recovered COVID-19 Patients with Comorbidities.Pathogens. 2022 Sep 30;11(10):1128. doi: 10.3390/pathogens11101128. Pathogens. 2022. PMID: 36297185 Free PMC article.
References
-
- Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020;368:473–474. - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous