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. 2021 Mar;93(3):1459-1464.
doi: 10.1002/jmv.26429. Epub 2020 Aug 21.

Late onset infectious complications and safety of tocilizumab in the management of COVID-19

Natasha N Pettit  1 , Cynthia T Nguyen  1 , Gökhan M Mutlu  2 , David Wu  2 , Lucas Kimmig  2 , David Pitrak  3 , Kenneth Pursell  3
Affiliations

Late onset infectious complications and safety of tocilizumab in the management of COVID-19

Natasha N Pettit et al. J Med Virol. 2021 Mar.

Abstract

Background: Tocilizumab (TCZ) has been used in the management of COVID-19-related cytokine release syndrome (CRS). Concerns exist regarding the risk of infections and drug-related toxicities. We sought to evaluate the incidence of these TCZ complications among COVID-19 patients.

Methods: All adult inpatients with COVID-19 between 1 March and 25 April 2020 that received TCZ were included. We compared the rate of late-onset infections (>48 hours following admission) to a control group matched according to intensive care unit admission and mechanical ventilation requirement. Post-TCZ toxicities evaluated included: elevated liver function tests (LFTs), GI perforation, diverticulitis, neutropenia, hypertension, allergic reactions, and infusion-related reactions.

Results: Seventy-four patients were included in each group. Seventeen infections in the TCZ group (23%) and 6 (8%) infections in the control group occurred >48 hours after admission (P = .013). Most infections were bacterial with pneumonia being the most common manifestation. Among patients receiving TCZ, LFT elevations were observed in 51%, neutropenia in 1.4%, and hypertension in 8%. The mortality rate among those that received TCZ was greater than the control (39% versus 23%, P = .03).

Conclusion: Late onset infections were significantly more common among those receiving TCZ. Combining infections and TCZ-related toxicities, 61% of patients had a possible post-TCZ complication. While awaiting clinical trial results to establish the efficacy of TCZ for COVID-19 related CRS, the potential for infections and TCZ related toxicities should be carefully weighed when considering use.

Keywords: Il-6 inhibition; SARS coronavirus; coronavirus; cytokine/chemokine; immune responses; tocilizumab.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
C‐reactive protein (CRP) trends post TCZ. * Excludes CRP values below the limit of detection (<3mg/L). TCZ, Tocilizumab
Figure 2
Figure 2
Ferritin trend post‐TCZ. TCZ, Tocilizumab
Figure 3
Figure 3
D‐dimer trend post‐TCZ. *Excludes D‐Dimer values above (>20 mg/L) or below (<0.27 mg/L) the limit of detection/reporting. TCZ, Tocilizumab
See this image and copyright information in PMC

References

    1. Chen X, Zhao B, Qu Y, et al. Detectable serum SARS‐CoV‐2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL‐6) level in critically ill COVID‐19 patients [published online ahead of print April 17, 2020]. Clin Infect Dis. 2020:ciaa449. https://pubmed.ncbi.nlm.nih.gov/32301997/ - PMC - PubMed
    1. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID‐19) outbreak. J Autoimmun. 2020;109:102433. 10.1016/j.jaut.2020.102433 - DOI - PMC - PubMed
    1. Xu X, Han M, Li T, et al. Effective treatment of severe COVID‐19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020;117(20):10970‐10975. 10.1073/pnas.2005615117 - DOI - PMC - PubMed
    1. Dastan F, Nadji SA, Saffaei A, Tabarsi P. Tocilizumab administration in a refractory case of COVID‐19. Int J Antimicrob Agents. 2020;56:106043. 10.1016/j.ijantimicag.2020.106043 - DOI - PMC - PubMed
    1. Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID‐19: a single center experience. J Med Virol. 2020;92(7):814‐818. 10.1002/jmv.25801 - DOI - PMC - PubMed

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