We aimed to evaluate the relation between admission COVID-19 associated hyperinflammatory syndrome (cHIS) score and intensive care unit (ICU) outcomes.
Materials and Methods
Patients with laboratory confirmed COVID-19 admitted to our ICU between 20th March 2020-15th June 2021 were included. Patients who received immunomodulatory treatment except corticosteroids were excluded. Main outcomes were ICU mortality and invasive mechanical ventilation (IMV) requirement after ICU admission.
Results
Three hundred and seventy patients with a median (IQR) age of 66 (56-77) were analyzed. Median admission cHIS score was 3 (2-4). A cHIS score ≥3 was found to be associated with ICU mortality (sensitivity = 0.63, specificity = 0.50; p < 0.01) and IMV requirement after ICU admission (sensitivity = 0.61, specificity = 0.51; p < 0.01). Patients with an admission cHIS score ≥3 (n = 199) had worse median admission APACHEII, SOFA scores and PaO2/FiO2 ratio than others (n = 171) (p < 0.01). IMV requirement after ICU admission (38.5% vs 26.1%;p = 0.03), ICU (36.2% vs 25.1%;p = 0.02), hospital (39.1% vs 26.9%;p = 0.01) and 28th day (28.1% vs 19.1%;p = 0.04) mortality were higher in patients with admission cHIS score ≥3 than others (p < 0.01). Age <65 years, malignancy and higher admission SOFA score were independent variables associated with admission cHIS score ≥3.
Conclusion
Critically-ill COVID-19 patients with admission cHIS score ≥3 have worse disease severity and outcomes than other patients.
RetamozoSBrito-ZerónPSisó-AlmirallAet al.Haemophagocytic syndrome and COVID-19. Clin Rheumatol. 2021;40(4):1233-1244. doi:10.1007/s10067-020-05569-4
4.
AfrinLBWeinstockLBMolderingsGJ. COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020;100(1):327-332. doi:10.1016/j.ijid.2020.09.016
5.
WebbBJPeltanIDJensenP, et al. Clinical criteria for COVID-19-associated hyperinflammatory syndrome: A cohort study. Lancet Rheumatol. 2020;2(12):e754-e763. doi:10.1016/S2665-9913(20)30343-X
6.
ChiuCHChangYHChangFY, et al. Humoral, cellular and cytokine immune responses against SARS-CoV-2 variants in COVID-19 convalescent and confirmed patients with different disease severities. Front Cell Infect Microbiol. 2022;12:862656. doi:10.3389/fcimb.2022.862656
7.
ChenHXieJSuN, et al. Corticosteroid therapy is associated with improved outcome in critically ill patients with COVID-19 with hyperinflammatory phenotype. Chest. 2021;159(5):1793-1802. doi:10.1016/j.chest.2020.11.050
8.
CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): A randomised controlled trial. Lancet Respir Med. 2021;9(3):295‐304. doi:10.1016/S2213-2600(20)30556-7
9.
Della-TorreECampochiaroCCavalliG, et al. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: An open-label cohort study. Ann Rheum Dis. 2020;79(10):1277-1285. doi:10.1136/annrheumdis-2020-218122
10.
HermineOMarietteXTharauxPLResche-RigonMPorcherRRavaudP. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia. JAMA Intern Med. 2021;181(1):1-9. doi:10.1001/jamainternmed.2020.6820
11.
RosasIOBräuNWatersM, et al. Tocilizumab in hospitalized patients with severe COVID-19 pneumonia. N Engl J Med, 2021; 384(16):1503-1516. doi:10.1056/NEJMoa2028700
12.
Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial and updated meta-analysis. Lancet. 2022;400(10349):359-368. doi:10.1016/S0140-6736(22)01109-6
13.
KellerMJKitsisEAAroraS, et al. Effect of systemic glucocorticoids on mortality or mechanical ventilation in patients with COVID-19. J Hosp Med. 2020;15(8):489-493.
14.
CamonAMAlonsoRMuñozFJ, et al. C-reactive protein cut-off for early tocilizumab and dexamethasone prescription in hospitalized patients with COVID-19. Sci Rep. 2022;12(1):5250. doi:10.1038/s41598-022-08882-x
15.
ReiffDDCronRQ. Performance of cytokine storm syndrome scoring systems in pediatric COVID-19 and multisystem inflammatory syndrome in children. ACR Open Rheumatol. 2021;3(12):820-826. doi:10.1002/acr2.11331
16.
CappaneraSPalumboMKwanSH, et al. When does the cytokine storm begin in COVID-19 patients? A quick score to recognize it. J Clin Med. 2021;10(2):297. doi:10.3390/jcm10020297
17.
SingerMDeutschmanCSSeymourCW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287
18.
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. Kdigo clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1-138.
19.
MacIntyreCRChughtaiAABarnesM, et al. The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09. BMC Infect Dis. 2018;18(1):637. doi:10.1186/s12879-018-3548-0
20.
GarbeeDDPierceSSManningJ. Opportunistic fungal infections in critical care units. Crit Care Nurs Clin North Am. 2017;29(1):67-79. doi:10.1016/j.cnc.2016.09.011
Giamarellos-BourboulisEJNeteaMGRovinaN, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992-1000.e3. doi:10.1016/j.chom.2020.04.009
23.
SiddiqiHKMehraMR. COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405-407. doi:10.1016/j.healun.2020.03.012
24.
LinLLuLCaoWLiT. Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020;9(1):727-732. doi:10.1080/22221751.2020.1746199
25.
Del ValleDMKim-SchulzeSHuangHH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643. doi:10.1038/s41591-020-1051-9
MortazETabarsiPJamaatiH, et al. Increased Serum levels of soluble TNF-α receptor is associated with ICU mortality in COVID-19 patients. Front Immunol. 2021;12:592727. doi:10.3389/fimmu.2021.592727
28.
WangJYangXLiYHuangJAJiangJSuN. Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction. Virol J. 2021;18(1):117. doi:10.1186/s12985-021-01588-y
29.
WanSXiangYFangW, et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol.2020;92(7):797-806. doi: 10.1002/jmv.25783
30.
DiaoBWangCTanY, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol. 2020;11:827. doi:10.3389/fimmu.2020.00827
31.
KamphuisEJuntTWaiblerZForsterRKalinkeU. Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia. Blood. 2006;108(10):3253-3261. doi:10.1182/blood-2006-06-027599
32.
ShiowLRRosenDBBrdickováN, et al. CD69 Acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature. 2006;440(7083):540–5544. doi:10.1038/nature04606
33.
FülöpTDupuisGWitkowskiJMLarbiA. The role of immunosenescence in the development of age-related diseases. Rev Invest Clin. 2016;68(2):84-91.
34.
FranceschiCSalvioliSGaragnaniPde EguileorMMontiDCapriM. Immunobiography and the heterogeneity of immune responses in the elderly: A focus on inflammaging and trained immunity. Front Immunol. 2017;8:982. doi:10.3389/fimmu.2017.00982
35.
FulopTLarbiAHirokawaKCohenAAWitkowskiJM. Immunosenescence is both functional/adaptive and dysfunctional/maladaptive. Semin Immunopathol. 2020;42(5):521-536. doi:10.1007/s00281-020-00818-9
36.
SantoroABientinesiEMontiD. Immunosenescence and inflammaging in the aging process: Age-related diseases or longevity?Ageing Res Rev. 2021;71:101422. doi:10.1016/j.arr.2021.101422
37.
StrangPHedmanCAdlitzerHSchultzT. Dying from cancer with COVID-19: Age, sex, socio-economic status, and comorbidities. Acta Oncol (Madr).2021;60(8):1019-1024. doi:10.1080/0284186X.2021.1934536
38.
TianJYuanXXiaoJ, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in wuhan, China: A multicentre, retrospective, cohort study. Lancet Oncol. 2020;21(7):893-903. doi:10.1016/S1470-2045(20)30309-0
39.
YamamotoTKawadaKObamaK. Inflammation-Related biomarkers for the prediction of prognosis in colorectal cancer patients. Int J Mol Sci. 2021;22(15):8002. doi:10.3390/ijms22158002
40.
DettorreGMDollySLoizidouA, et al. Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: The OnCovid inflammatory score. J Immunother Cancer. 2021;9(3):e002277. doi:10.1136/jitc-2020-002277
41.
HalacliBUnverNHalacliSO, et al. Investigation of hemophagocytic lymphohistiocytosis in severe sepsis patients. J Crit Care. 2016;35:185-190. doi:10.1016/j.jcrc.2016.04.034
42.
SimonnetAEngelmannIMoreauAS, et al. High incidence of Epstein–Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19. Infect Dis Now. 2021;51(3):296-299. doi:10.1016/j.idnow.2021.01.005
43.
LehnerGFKleinSJZollerHPeerABellmannRJoannidisM. Correlation of interleukin-6 with Epstein-Barr virus levels in COVID-19. Crit Care. 2020;24(1):657. doi:10.1186/s13054-020-03384-6
44.
NaendrupJHGarcia BorregaJEichenauerDAShimabukuro-VornhagenAKochanekMBöllB. Reactivation of EBV and CMV in severe COVID-19—epiphenomena or trigger of hyperinflammation in need of treatment? A large case series of critically ill patients. J Intensive Care Med. 2022;37(9):1152-1158. doi:10.1177/08850666211053990
45.
van de VeerdonkFLGiamarellos-BourboulisEPickkersP, et al. A guide to immunotherapy for COVID-19. Nat Med. 2022;28(1):39-50. doi:10.1038/s41591-021-01643-9
46.
HorbyPLimWS, Emberson JR, RECOVERY Collaborative Group, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436
47.
AngusDCDerdeLAl-BeidhF, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA. 2020;324(13):1317-1329. doi:10.1001/jama.2020.17022
48.
LansburyLERodrigoCLeonardi-BeeJNguyen-Van-TamJShen LimW. Corticosteroids as adjunctive therapy in the treatment of influenza: An updated cochrane systematic review and meta-analysis. Crit Care Med. 2020;48(2):e98-e106. doi:10.1097/CCM.0000000000004093
49.
MorenoGCarbonellRMartin-LoechesI, et al. Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: A multicentre cohort study. Ann Intensive Care. 2021;11(1):159. doi:10.1186/s13613-021-00951-0
50.
MorenoGRuiz-BotellaMMartín-LoechesI, et al. A Differential Therapeutic consideration for use of Corticosteroids according to Established COVID-19 Clinical Phenotypes in Critically ill Patients. Med Intensiva. 2021;10:1016. doi:10.1016/j.medin.2021.10.002
51.
StoneJHFrigaultMJSerling-BoydNJ, et al. Efficacy of tocilizumab in patients hospitalized with COVID-19. N Engl J Med. 2020;383(24):2333-2344. doi:10.1056/NEJMoa2028836
52.
KharazmiABMoradiOHaghighiM, et al. A randomized controlled clinical trial on efficacy and safety of anakinra in patients with severe COVID-19. Immun Inflamm Dis. 2022;10(2):201-208. doi:10.1002/iid3.563
53.
BoregowdaUPerisettiANanjappaAGajendranMKutti SridharanGGoyalH. Addition of tocilizumab to the standard of care reduces mortality in severe COVID-19: A systematic review and meta-analysis. Front Med (Lausanne). 2020;7:586221. doi:10.3389/fmed.2020.586221
54.
GordonACMounceyPR, Al-Beidh F, REMAP-CAP Investigators, et al. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. N Engl J Med. 2021;384(16):1491-1502. doi:10.1056/NEJMoa2100433
55.
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-1645. doi:10.1016/S0140-6736(21)00676-0
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
