Generic placeholder image

Current Respiratory Medicine Reviews

Editor-in-Chief

ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Research Article

Mortality Predictors of Pre-variant SARS-CoV-2 Infected ARDS Patients Receiving Favipiravir and Tocilizumab

Author(s): Fatma Yildirim*, Irem Karaman, Muhammed Apaydin, Halil Ibrahim Dural and Meltem Simsek

Volume 19, Issue 2, 2023

Published on: 07 April, 2023

Page: [128 - 137] Pages: 10

DOI: 10.2174/1573398X19666230320164227

Price: $65

Abstract

Objective: In this study, we investigated the risk factors affecting mortality of critically ill COVID-19-related acute respiratory distress syndrome (ARDS) patients who were followed up in the intensive care unit (ICU) and received tocilizumab and favipiravir treatments together before vaccination.

Materials and Methods: The data of patients who were followed up and treated between 1, July 2020 and 5, October 2020 were retrospectively analyzed. Demographic data of the patients (age, gender), acute physiology and chronic health evaluation score II (APACHE II), sequential organ failure assessment (SOFA) score, RT-PCR of oro-nasopharyngeal swabs, the severity of ARDS on the day of tocilizumab admission, time from RT-PCR positivity to tocilizumab administration, respiratory support treatments, all other medical treatments, and ICU outcomes were recorded. Risk factors affecting mortality were evaluated with multiple regression analysis.

Results: A total of 60 patients with a median age of 69.8 (24-87) years, 25 females and 35 males were included in the study. The mean APACHE II score was 18.9 ± 8.0, and the SOFA score was 4.5 ± 2.0. Fifty-two (86.7%) patients had positive oro-nasopharyngeal swabs for SARS-CoV-2 by RT-PCR; (13,3%) patients had positive IgM/Ig G rapid antibody tests for SARS-CoV-2. Tocilizumab was given on an average of 2.5th days (± 2.0 days). On the day of tocilizumab administration, 1 (1.7%) patient had mild ARDS, 30 (50.0%) had moderate ARDS, and 29 (48.3%) had severe ARDS. The PaO2/FIO2 ratio of the study group on the day of tocilizumab administration was 96.7 ± 36.6 mmHg. Thirty-four (56.7%) patients were intubated during follow-up. Forty (66.7%) patients died, while 20 (33.3%) patients were transferred to the ward. The mean length of stay in the ICU was 11.4 ± 5.5 days. Advanced age (Hazard ratio (HR) 1.8; 95% confidence interval (CI) 0.88-0.93; p < 0.001), higher APACHE II score (HR 0.81, 95% CI 0.74-0.98; p = 0.001), higher SOFA score on the day of tocilizumab administration (HR 1.47, 95% CI 0.39-0.79; p = 0.001), and lower PaO2/FIO2 ratio (HR 2.54, 95% CI 2.33-3.79; p < 0.001) were determined as independent risk factors for mortality.

Conclusion: Patients administered tocilizumab and favipiravir in our ICU were mostly patients with moderate-severe ARDS and had higher inflammatory markers. The reason for the high mortality in this study was attributed to the fact that all of the patients had moderate-severe COVID-19-related ARDS, rather than severe COVID-19.

Graphical Abstract

[1]
WHO COVID-19 Dashboard. Geneva: World Health Organization 2020. Available from: https://covid19.who.int/
[2]
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020; 395(10229): 1054-62.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[3]
Bhatraju PK, Ghassemieh BJ, Nichols M, et al. COVID-19 in critically Ill patients in the seattle region-case series. N Engl J Med 2020; 382(21): 2012-22.
[http://dx.doi.org/10.1056/NEJMoa2004500] [PMID: 32227758]
[4]
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020; 8(5): 475-81.
[http://dx.doi.org/10.1016/S2213-2600(20)30079-5] [PMID: 32105632]
[5]
Sun X, Wang T, Cai D, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020; 53: 38-42.
[http://dx.doi.org/10.1016/j.cytogfr.2020.04.002] [PMID: 32360420]
[6]
Yang PH, Ding YB, Xu Z, et al. Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19. Infect Dis Poverty 2020; 9(1): 161.
[http://dx.doi.org/10.1186/s40249-020-00780-6]
[7]
Cascella M, Mauro I, De Blasio E, et al. Rapid and impressive response to a combined treatment with single-dose tocilizumab and NIV in a patient with COVID-19 pneumonia/ARDS. Medicina 2020; 56(8): 377.
[http://dx.doi.org/10.3390/medicina56080377]
[8]
Zhang X, Song K, Tong F, et al. First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv 2020; 4(7): 1307-10.
[http://dx.doi.org/10.1182/bloodadvances.2020001907] [PMID: 32243501]
[9]
Buonaguro FM, Puzanov I, Ascierto PA. Anti-IL6R role in treatment of COVID-19-related ARDS. J Transl Med 2020; 18(1): 165.
[http://dx.doi.org/10.1186/s12967-020-02333-9]
[10]
Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev 2020; 19(7)102568
[http://dx.doi.org/10.1016/j.autrev.2020.102568] [PMID: 32376398]
[11]
Hermine O, Mariette X, Tharaux PL, et al. Effect of tocilizumab vs. usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia. JAMA Intern Med 2021; 181(1): 32-40.
[http://dx.doi.org/10.1001/jamainternmed.2020.6820] [PMID: 33080017]
[12]
Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with COVID-19. N Engl J Med 2020; 383(24): 2333-44.
[http://dx.doi.org/10.1056/NEJMoa2028836] [PMID: 33085857]
[13]
Gordon AC, Mouncey PR, Al-Beidh F, et al. Interleukin-6 receptor antagonists in critically Ill patients with covid-19. N Engl J Med 2021; 384(16): 1491-502.
[http://dx.doi.org/10.1056/NEJMoa2100433] [PMID: 33631065]
[14]
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021; 397(10285): 1637-45.
[http://dx.doi.org/10.1016/S0140-6736(21)00676-0] [PMID: 33933206]
[15]
Hsu JY, Mao YC, Liu PY, Lai KL. Pharmacology and adverse events of emergency-use authorized medication in moderate to severe COVID-19. Pharmaceuticals 2021; 14(10): 955.
[http://dx.doi.org/10.3390/ph14100955]
[16]
COVID-19 Interim Guidance (TC Sağlık Bakanlığı COVID-19 (SARS-CoV-2 Enfeksiyonu) Rehberi). Republic of Turkey Ministry of Health 2020. Available from: https://covid19bilgi.saglik. gov.tr/depo/rehberler/COVID-19_Rehberi.pdf?type=file
[17]
Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: The Berlin Definition. JAMA 2012; 307(23): 2526-33.
[http://dx.doi.org/10.1001/jama.2012.5669] [PMID: 22797452]
[18]
Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). JAMA 2020; 324(8): 782-93.
[http://dx.doi.org/10.1001/jama.2020.12839] [PMID: 32648899]
[19]
Koutsakos M, Kedzierska K. A race to determine what drives COVID-19 severity. Nature 2020; 583(7816): 366-8.
[http://dx.doi.org/10.1038/d41586-020-01915-3] [PMID: 32661414]
[20]
Jordan SC, Zakowski P, Tran HP, et al. Compassionate use of tocilizumab for treatment of SARS-CoV-2 pneumonia. Clin Infect Dis 2020; 71(12): 3168-73.
[http://dx.doi.org/10.1093/cid/ciaa812] [PMID: 32575124]
[21]
Zhao J, Cui W, Tian BP. Efficacy of tocilizumab treatment in severely ill COVID-19 patients. Crit Care 2020; 24(1): 524.
[http://dx.doi.org/10.1186/s13054-020-03224-7]
[22]
Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with cOVID-19. Clin Infect Dis 2021; 73(2): e445-54.
[http://dx.doi.org/10.1093/cid/ciaa954] [PMID: 32651997]
[23]
Sciascia S, Aprà F, Baffa A, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol 2020; 38(3): 529-32.
[PMID: 32359035]
[24]
Alattar R, Ibrahim TBH, Shaar SH, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol 2020; 92(10): 2042-9.
[http://dx.doi.org/10.1002/jmv.25964] [PMID: 32369191]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy