Therapeutic Safety and Efficacy of Triple-immunosuppressants Versus Dual-immunosuppressants in Severe-to-critical COVID-19: a Prospective Cohort Study in Bangladesh

Overview

Journal Ann Med

Publisher Informa Healthcare

Specialty General Medicine

Date 2022 Mar 3

PMID 35238257

Authors

Md Jahidul Hasan

Raihan Rabbani

Ahmad Mursel Anam

Shihan Mahmud Redwanul Huq

Affiliations

Soon will be listed here.

Abstract

Background: Hyperinflammation-induced respiratory failure is a leading cause of mortality in COVID-19 infection. Immunosuppressants such as, Baricitinib and interleukin inhibitors are the drug-of-choice to suppress cytokine storm in COVID-19. Here, we compared the therapeutic safety and efficacy of triple-immunosuppressants with dual-immunosuppressants in patients with severe-to-critical COVID-19.

Methods: This study was conducted on 103 confirmed COVID-19 patients. Of 103 patients, 49 (N) and 54 (N) patients received dual-immunosuppressants (baricitinib plus two doses of secukinumab) and triple immunosuppressants (baricitinib plus single dose of tocilizumab and secukinumab) in group A and group B, respectively. Groups were compared in terms of clinical outcome, critical support-requirement, survival, re-hospitalisation, and adverse events (AEs).

Results: Patients in group B achieved normal blood oxygen saturation level (SpO) earlier than the patients of group A [4 day (IQR: 3-12) vs 5 day (IQR: 5-14), < .05]. The requirement of intensive care unit (ICU) and mechanical ventilation (MV) support was less in group B than group A [16.7%/28.6%, 11.1%/18.4%, respectively < .05]]. The incidence of COVID-19 acute respiratory distress syndrome and 60-day all cause mortality was reduced in group B compared to group A [0.43 (0.19-0.98), < .05; 0.35 (0.08-1.44), > .05]. The 60-day re-hospitalisation rate was two-fold high in group A than group B ( = .024). Immunosuppressant-associated adverse events and secondary bacterial/fungal infections were relative high in patients of group B.

Conclusions: Triple-immunosuppressants in severe-to-critical COVID-19 infection exhibited better clinical outcome; reduced ICU and MV requirement; shorter hospital stay with deceased 60-day all cause mortality and re-hospitalisation compared to dual-immunosuppressants.

References

Coperchini F, Chiovato L, Rotondi M . Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One!. Front Immunol. 2021; 12:668507. PMC: 8107352. DOI: 10.3389/fimmu.2021.668507. View

Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G . Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med. 2020; 180(10):1345-1355. PMC: 7364371. DOI: 10.1001/jamainternmed.2020.3539. View

Hasan M, Rabbani R, Anam A, Huq S, Polash M, Nessa S . Impact of high dose of baricitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh. BMC Infect Dis. 2021; 21(1):427. PMC: 8102838. DOI: 10.1186/s12879-021-06119-2. View

Richardson S, Hirsch J, Narasimhan M, Crawford J, McGinn T, Davidson K . Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020; 323(20):2052-2059. PMC: 7177629. DOI: 10.1001/jama.2020.6775. View

Bartoli A, Gabrielli F, Alicandro T, Nascimbeni F, Andreone P . COVID-19 treatment options: a difficult journey between failed attempts and experimental drugs. Intern Emerg Med. 2021; 16(2):281-308. PMC: 7781413. DOI: 10.1007/s11739-020-02569-9. View

Olivas-Martinez A, Cardenas-Fragoso J, Jimenez J, Lozano-Cruz O, Ortiz-Brizuela E, Tovar-Mendez V . In-hospital mortality from severe COVID-19 in a tertiary care center in Mexico City; causes of death, risk factors and the impact of hospital saturation. PLoS One. 2021; 16(2):e0245772. PMC: 7857625. DOI: 10.1371/journal.pone.0245772. View

Karia R, Gupta I, Khandait H, Yadav A, Yadav A . COVID-19 and its Modes of Transmission. SN Compr Clin Med. 2020; 2(10):1798-1801. PMC: 7461745. DOI: 10.1007/s42399-020-00498-4. View

Tzotzos S, Fischer B, Fischer H, Zeitlinger M . Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey. Crit Care. 2020; 24(1):516. PMC: 7441837. DOI: 10.1186/s13054-020-03240-7. View

Armstrong R, Kane A, Kursumovic E, Oglesby F, Cook T . Mortality in patients admitted to intensive care with COVID-19: an updated systematic review and meta-analysis of observational studies. Anaesthesia. 2021; 76(4):537-548. PMC: 8013495. DOI: 10.1111/anae.15425. View

10.

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S . Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020; 180(7):934-943. PMC: 7070509. DOI: 10.1001/jamainternmed.2020.0994. View

11.

Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G . COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol. 2020; 51(6):613-628. PMC: 7533045. DOI: 10.1007/s10735-020-09915-3. View

12.

Bhatraju P, Ghassemieh B, Nichols M, Kim R, Jerome K, Nalla A . Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020; 382(21):2012-2022. PMC: 7143164. DOI: 10.1056/NEJMoa2004500. View

13.

Wang Y, Lu X, Li Y, Chen H, Chen T, Su N . Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19. Am J Respir Crit Care Med. 2020; 201(11):1430-1434. PMC: 7258632. DOI: 10.1164/rccm.202003-0736LE. View

14.

Wu Z, McGoogan J . Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13):1239-1242. DOI: 10.1001/jama.2020.2648. View

15.

Li X, Ma X . Acute respiratory failure in COVID-19: is it "typical" ARDS?. Crit Care. 2020; 24(1):198. PMC: 7202792. DOI: 10.1186/s13054-020-02911-9. View

16.

Rosas J, Liano F, Canto M, Barea J, Beser A, Rabasa J . Experience With the Use of Baricitinib and Tocilizumab Monotherapy or Combined, in Patients With Interstitial Pneumonia Secondary to Coronavirus COVID19: A Real-World Study. Reumatol Clin (Engl Ed). 2020; . PMC: 7699160. DOI: 10.1016/j.reuma.2020.10.009. View

17.

Hasan M, Rabbani R, Anam A, Huq S . Secukinumab in severe COVID-19 pneumonia: Does it have a clinical impact?. J Infect. 2021; 83(1):e11-e13. PMC: 8139439. DOI: 10.1016/j.jinf.2021.05.011. View

18.

Rowaiye A, Okpalefe O, Onuh Adejoke O, Ogidigo J, Oladipo O, Ogu A . Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications. J Inflamm Res. 2021; 14:1487-1510. PMC: 8057798. DOI: 10.2147/JIR.S301784. View

19.

Grasselli G, Scaravilli V, Mangioni D, Scudeller L, Alagna L, Bartoletti M . Hospital-Acquired Infections in Critically Ill Patients With COVID-19. Chest. 2021; 160(2):454-465. PMC: 8056844. DOI: 10.1016/j.chest.2021.04.002. View

20.

Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo F, Chong M . Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020; 323(16):1612-1614. PMC: 7082763. DOI: 10.1001/jama.2020.4326. View