Abstract

Background: Due to uncontrolled lymphocyte reaction, the overproduction of cytokines in COVID-19 patients can cause sepsis-like symptoms, suggesting sepsis, CRS, and sHLH. Since different therapeutic approaches are used for each diagnosis, differentiation is essential. This study aims to use H-score as a possible predictive prognosis tool in COVID-19 patients.

Method: A sample of 64 moderate and severe COVID-19 patients enrolled in this study. Clinical and laboratory findings were assessed. H-score was calculated initially and was reevaluated among severe cases 72 hours later and in moderate cases showing severe COVID-19 features.

Result: 64 COVID-19 patients presented with 32 moderate and 32 severe cases with a median age of 57.78 years old. Mortality of 31.3% was reported. Laboratory findings including TG, ferritin, and AST showed significantly higher initial and follow-up laboratory assessment levels in severe cases than moderate cases. Moreover, fibrinogen was significantly higher among severe cases than moderate cases at the initial assessment, but no significant difference was reported in the second fibrinogen assessment. In this study, the initial H-score was significantly higher among severe cases than moderated cases. Moreover, demised cases showed a higher initial H-score than surviving patients.

Conclusion: In this study, H-score was useful as a predictive tool for the initial evaluation of severe COVID-19 cases. H-score is much lower in these patients than non-COVID-19 HLH patients may be due to the different underlying immunologic pathophysiology of COVID-19; thus, each H-score criterion must be evaluated for sensitivity and specificity in COVID-19 patients. Following that, with the modifications in the H-score cut-offs, H-score may be useful for diagnosing immune overreaction and determining the need for more exclusive immunomodulatory treatments.

Keywords: Hemophagocytic Lymphohistocytosis Hscore COVID-19 References

1. Organization WH. WHO Coronavirus (COVID-19) Dashboard 2022 [Available from: https://covid19.who.int/.
2. Cappanera S, Palumbo M, Kwan SH, Priante G, Martella LA, Saraca LM, et al. When does the cytokine storm begin in COVID-19 patients? A quick score to recognize it. Journal of Clinical Medicine. 2021;10(2):1-12.
3. Gürsoy B, Sürmeli CD, Alkan M, Satıcı C, Altunok ES, Kamat S, et al. Cytokine storm in severe COVID-19 pneumonia. Journal of medical virology. 2021;93(9):5474-80.
4. Moghadas SM, Vilches TN, Zhang K, Wells CR, Shoukat A, Singer BH, et al. The impact of vaccination on COVID-19 outbreaks in the United States. medRxiv. 2021.
5. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. The Journal of infection. 2020;80(6):607-13.
6. Kazemi MH, Dehaghi BK, Roshandel E, Bonakchi H, Parkhideh S, Mehdizadeh M, et al. Association of hscore parameters with severe COVID-19: A systematic review and meta-analysis. Iranian Journal of Medical Sciences. 2021;46(5):322-38.
7. Chu R, van Eeden C, Suresh S, Sligl WI, Osman M, Cohen Tervaert JW. Do COVID-19 Infections Result in a Different Form of Secondary Hemophagocytic Lymphohistiocytosis. International journal of molecular sciences. 2021;22(6).
8. Clark KEN, Nevin WD, Mahungu T, Lachmann H, Singh A. Assessment of the Hemophagocytic Lymphohistiocytosis HScore in Patients With Coronavirus Disease 2019. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021;73(9):e3110-e2.
9. Meng QF, Tian R, Long H, Wu X, Lai J, Zharkova O, et al. Capturing Cytokines with Advanced Materials: A Potential Strategy to Tackle COVID-19 Cytokine Storm. Advanced Materials. 2021;33(20).
10. Lorenz G, Moog P, Bachmann Q, La Rosée P, Schneider H, Schlegl M, et al. Title: Cytokine release syndrome is not usually caused by secondary hemophagocytic lymphohistiocytosis in a cohort of 19 critically ill COVID-19 patients. Scientific reports. 2020;10(1):18277.
11. Ardern-Jones MR, Stammers M, Phan HTT, Borca F, Koutalopoulou A, Teo Y, et al. Secondary haemophagocytic lymphohistiocytosis in hospitalised COVID-19 patients as indicated by a modified HScore is infrequent and high scores do not associate with increased mortality. Clinical Medicine, Journal of the Royal College of Physicians of London. 2021;21(5):E543-E7.
12. Meng M, Chen L, Zhang S, Dong X, Li W, Li R, et al. Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients. BMC Infectious Diseases. 2021;21(1).
13. Bordbar M, Sanaei Dashti A, Amanati A, Shorafa E, Mansoori Y, Dehghani SJ, et al. Assessment of the HScore as a predictor of disease outcome in patients with COVID-19. BMC Pulmonary Medicine. 2021;21(1).
14. Bhattacharjee S, Banerjee M, Pal R. COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate. Indian pediatrics. 2020;57(9):827-33.
15. Greco GF, Spreafico F, Di Costanzo D, Pecoriello A, Garuti M, Inglese F, et al. Hemophagocytic Lymphohistiocytosis in a Patient With Acute Respiratory Distress Syndrome Secondary to SARS-CoV-2 Infection. Journal of medical cases. 2020;11(10):327-9.
16. Caricchio R, Gallucci M, Dass C, Zhang X, Gallucci S, Fleece D, et al. Preliminary predictive criteria for COVID-19 cytokine storm. Annals of the rheumatic diseases. 2021;80(1):88-95.
17. Hakim NN, Chi J, Olazagasti C, Liu JM. Secondary hemophagocytic lymphohistiocytosis versus cytokine release syndrome in severe COVID-19 patients. Experimental biology and medicine (Maywood, NJ). 2021;246(1):5-9.
18. Gualdoni GA, Hofmann GA, Wohlfarth P, Winkler H-M, Winkler S, Haslacher H, et al. Prevalence and outcome of secondary hemophagocytic lymphohistiocytosis among SIRS patients: results from a prospective cohort study. Journal of clinical medicine. 2019;8(4):541.