Relationship between Corona Virus Infection and Immune Checkpoint Inhibitors

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Relationship between Corona Virus Infection and Immune Checkpoint Inhibitors


Shihori Tanabe*

Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan

*Corresponding author: Shihori Tanabe, Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan

Citation: Tanabe S. (2022) Relationship between coronavirus infection and immune checkpoint inhibitors. Adv Clin Med Res. 3(3):1-4.

Received: August 9,  2022 | Published: August 30, 2022

Copyright© 2022 genesis pub by Tanabe S. CC BY-NC-ND 4.0 DEED. This is an open-access article distributedunder the terms of the Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License.,This allows others distribute, remix, tweak, and build upon the work, even commercially, as long as they credit the authors for the original creation.



The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) causes infectious disease, COVID-19, and the relationship between COVID-19 and cancer immunotherapy such as immune checkpoint inhibitors (ICIs) is not fully understood. Recent rapid progress in ICI therapy has reported their immune response-related reaction, which demonstrates the importance of studies on the relationship between ICIs and COVID-19. In this Editorial, the application of ICIs in COVID-19 is focused on.


Immune checkpoint inhibitors (ICIs)

Recent advances in ICIs have great impacts on clinical application in many fields including cancer therapeutics and the toxicities [1-8]. The patients treated with ICIs alone or in combination with chemotherapy have some side effects, which demands the needs for the prognostic and predictive markers for ICI therapy [1]. ICIs have a variety of target antigens, where nivolumab, pembrolizumab, and cemiplimab target programmed death-1 (PD-1), whereas durvalumab, avelumab, and atezolizumab target PD-ligand 1 (PD-L1), and ipilimumab targets cytotoxic T lymphocyte-associated protein 4 (CTLA-4)[2]. Nivolumab-related pulmonary toxicity includes interstitial lung disease, pneumonitis, organizing pneumonia, pulmonary sarcoidosis, pulmonary infection reactivation, and asthma [2]. A pharmacovigilance cohort of ICI therapy revealed that the median time to onset of immune-related adverse events varies from 28 days in myocarditis to 112 days in diabetes [3]. Adverse drug reactions included myocarditis, myositis, neurologic, hepatitis, vasculitis, pneumonitis, colitis, thyroiditis, hematologic, uveitis, skin, mucositis, arthritis, nephritis, hypophysitis, pancreatitis, adrenal and diabetes [3]. ICI-associated myocarditis is characterized by arrhythmias/conduction disturbances, concomitant skeletal myositis and myasthenia gravis, and high mortality [4]. Pneumonitis is relatively uncommon but fetal in adverse effects of ICI treatment [5].

ICIs and COVID-19

Several recent studies have suggested the relationship between ICIs and COVID-19(9-18).A melanoma patient treated with nivolumab, an ICI, and bempegaldesleukin, PEGylated interleukin-2 (IL-2), developed COVID-19 pneumonia with no serious adverse outcome [9], however, modification of the immune response to COVID-19 by treatment with ICIs and bempegaldesleukin has been suggested [9]. Treatment with ICIs, tocilizumab plus pembrolizumab showed decreased time to clinical improvement in COVID-19 patients [10,11].Patients with lung cancer treated with ICIs demonstrated no increased incidence of immune-related adverse events associated with mRNA vaccines, while the vaccine immunogenicity was lower [12]. Pulmonary toxicity secondary to treatment of ICIs was similar to that of infectious pneumonia of COVID-19 [13]. Some similarities in neurotoxicity in cancer immunotherapy such as chimeric antigen receptor (CAR) T-cell therapy or ICIs and neurological manifestations of cytokine storms such as COVID-19-related encephalopathy have been suggested[14]. Serious adverse neurological events of ICIs include meningitis, encephalitis, demyelinating syndromes, central nervous system vasculitis, neuropathy, neuromuscular junction disorders, and myopathy [14]. Antibody and T-cell responses after COVID-19 vaccinations in a majority of solid tumor patients were equivalent to those of healthy donors [15]. A case report of a diabetic patient with refractory invasive fungal diseases after SARS-CoV-2 infection demonstrated that treatment with ICI and interferon greversed T cell exhaustion and enhance leukocytes activation, whereas careful consideration in immune-mediated adverse events is needed [16]. A cohort study in cancer patients demonstrated that the immune response to COVID vaccination is independent of the anti-cancer immune response in ICI treatment [17]. While the efficacy of mRNA vaccines for SARS-CoV-2 was not affected by the immunosuppression in cancer patients, the relationship between ICI and humoral response to mRNA vaccines in cancer patients needs to be investigated [18]. The lymphopenia occurs in treatment with temozolomide, ICIs, or other anti-cancer drugs, which may negatively affect the mortality with COVID-19[19]. As COVID-19 affects global concern, many cancer drugs including monoclonal antibodies, antibody-drug conjugates, CAR-T cell therapies, and ICIs have been approved in the COVID-19 pandemic [20]. Immune response and adverse effects of ICIs in COVID-19 need to be carefully monitored.


This research was supported by Japan Agency for Medical Research and Development (AMED), grant numbers JP21mk0101216, JP22mk0101216,JSPS KAKENHI grant number 21K12133, and Ministry of Health, Labour, and Welfare (MHLW), Japan. The author would like to thank all collaborators.


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