Effect of administering subsequent immune checkpoint inhibition in cancer patients with prior COVID-19 infection
Authors: Jianping Bi, Sheng Wang, Yajie Wang, Dongqin Yang, Vivek Verma, Jing Huang, Guang Han
Journal: Journal of Infection (2020)

We read with interest the recent article published by Skevaki C et al who described the laboratory characteristics of patients infected with the novel SARS-CoV-2 virus,1Skevaki C. Fragkou P.C. Cheng C. Xie M. Renz H. Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus.J Infect. 2020; 81: 205-212https://doi.org/10.1016/j.jinf.2020.06.039Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar which indicated that patients with COVID-19 have varying degrees of multiple organ dysfunction. Coronavirus disease 2019 (COVID-19) is characterized by symptomatology from immune hyperactivation against normal tissues such as the lungs. Because immune checkpoint inhibitors (ICIs) are intended to galvanize the immune system, it is imperative to evaluate the effect of ICI therapy in patients who have recovered from prior COVID-19. In this study, we collected and analyzed data from 8 cancer patients with SARS-CoV-2 infection history (negative for viral RNA and positive for serum antibodies) who received subsequent immunotherapy from four hospitals, including Hubei Cancer Hospital, Union Hospital, People's Hospital of Dongxihu District and The Fifth Hospital of Wuhan. All patients had been diagnosed with COVID-19 via positive for nucleic acid testing before. We reviewed the medical records, including SARS-CoV-2 nucleic acid and antibody testing, chest computed tomography (CT), biochemical markers, and routine bloodwork and treatment data of all cancer patients with prior COVID-19 infection from March 9 to July 29, 2020. Confirmation of prior COVID-19 infection was defined as positive SARS-CoV-2 antibody testing by the colloidal gold immunoassay (Innovita, Tangshan, Hebei, China) and negative for viral nucleic acid by real-time reverse transcriptase PCR (rRT-PCR). The median age was 58 years (range: 41–72), and 63% patients were men. Four (50%) patients had a history of smoking and three (38%) patients had chronic diseases. All cases harbored positive serum antibodies: 1 was negative for immunoglobulin G (IgG−) and positive for immunoglobulin M (IgM+), 6 were IgG+ IgM− and 1 was IgG+ IgM+. Nasopharyngeal cancer was the most frequent neoplasm (3/8 [38%] patients), followed by lung cancer (2/8 [25%] patients) (Table 1). Two (25%) patients had received ICI therapy prior to initially developing COVID-19, and 6 (75%) patients were ICI therapy-naïve.Table 1Clinical characteristics of cancer patients receiving systemic therapy with prior SARS-CoV-2 infection.Patient No.SexAgePSCancer diagnosisStagingChronic diseasesSystemic therapyTime of nucleic acid testing1Female591NPCrT0N1M0None2 cycles of GP and 2 cycles of GP +PD-1 inhibitorApril 21; May 15; June 3; June 6; June 30; July 202Male411NPCT3N2M0None2 cycles of GP + PD-1 inhibitor; radiotherapy + 2 cycles of DDP + PD-1 inhibitorMarch 25; April 17; May 293Female481NPCT3N1M0NoneRadiotherapy + 2 cycles of PD-1 inhibitor; 1 cycle of TPApril 26, May 8; June 10; June 154Male721NSCLCT3N1M0Hypertension; Cardiovascular disease; COPD2 cycles of abraxane and 2 cycles of abraxane + nedaplatin + PD-1 inhibitorMarch 23; April 1; April 3; May 5; June 3; June 295Male641NSCLCT2N2M0Cardiovascular disease2 cycles of PD-1 inhibitorApril 18; May 12; May 26; June 9; July 176Male711Soft tissue sarcomaT3N0M0 G3None2 cycles of gemcitabine + anlotinib + PD-1 inhibitorMay 20; June 3; June 4; June 297Female511Rectal cancerrT0N0M1None4 cycles of XELOX + PD-1 inhibitorApril 16; May 5; May 29; July 18Male571Esophagus cancerT4aN2M0Hypertension; Diabetes3 cycles of capecitabine + nedaplatin + PD-1 inhibitorMarch 20; June 1; July 2Abbreviations: NPC, nasopharyngeal cancer; NSCLC, non-small cell lung cancer; COPD, chronic obstructive pulmonary disease; GP, gemcitabine and cisplatin; PD-1, programmed cell death protein 1; XELOX, oxaliplatin + capecitabine. Open table in a new tab Abbreviations: NPC, nasopharyngeal cancer; NSCLC, non-small cell lung cancer; COPD, chronic obstructive pulmonary disease; GP, gemcitabine and cisplatin; PD-1, programmed cell death protein 1; XELOX, oxaliplatin + capecitabine. Three (38%) patients received a combination of anti-PD-1 agents with chemotherapy. Two (25%) patients were treated with immunotherapy alone. Two (25%) patients received combinatorial anti-PD-1 ICI with radiotherapy ± chemotherapy. One (13%) patient received anti-PD-1 with anlotinib. The median follow-up from initial administration of ICI therapy was 83 days (IQR: 64–98). At the time of last follow-up, all patients remained negative for SARS-CoV-2 RNA nucleic acid, without suspicious changes on chest CT. Five (63%) patients experienced altered immunoglobulin test results. Specifically, 3 (38%) patients who were initially IgG+ IgM−became IgG−IgM− after 25, 42, and 62 days of ICI therapy. Another was initially IgG+ IgM+ but became IgG+ IgM−after 23 days, and the final patient (initially IgG− IgM+) became IgG− IgM− following 28 days of ICI therapy. Systemic therapies were tolerated well in this cohort. Three patients developed grade 2 myelosuppression and one patient had hypothyroidism. Only one patient had grade 3 myelosuppression. Cancer patients are a vulnerable population to COVID-19, and delaying therapies such as ICIs risks disease progression. It have reported that SARS-CoV-2 can reemerge in recovered (with negative viral RNA) patients,2Lan L. Xu D. Ye G. et al.Positive RT-PCR test results in patients recovered from COVID-19 [published online ahead of print, 2020 Feb 27].JAMA. 2020; 323: 1502-1503https://doi.org/10.1001/jama.2020.2783Crossref PubMed Scopus (886) Google Scholar and some studies have reported hepatitis B virus (HBV) or tuberculosis reactivation in cancer patients undergoing ICI therapy.3Tsai C.C. Chen J.H. Wang Y.C. Chang F.Y. Re-activation of pulmonary tuberculosis during anti-programmed death-1 (PD-1) treatment.QJM. 2019; 112: 41-42https://doi.org/10.1093/qjmed/hcy243Crossref PubMed Scopus (15) Google Scholar, 4Zhang X. Zhou Y. Chen C. et al.Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition.J Immunother Cancer. 2019; 7 (Published 2019 Nov 21): 322https://doi.org/10.1186/s40425-019-0808-5Crossref PubMed Scopus (110) Google Scholar Thus, it became essential to evaluate the safety of ICIs in patients recovered from prior COVID-19 infection. Importantly, this study did not observe a single case of disease reactivation or immune hyperactivation from ICI therapy. Patients with COVID-19 have varying degrees of multiple organ dysfunction.5Guo T. Fan Y. Chen M. et al.Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) [published online ahead of print, 2020 Mar 27].JAMA Cardiol. 2020; 5: 1-8https://doi.org/10.1001/jamacardio.2020.1017Crossref Scopus (2836) Google Scholar,6Yang 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 [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26].Lancet Respir Med. 2020; 8: 475-481https://doi.org/10.1016/S2213-2600(20)30079-5Abstract Full Text Full Text PDF PubMed Scopus (6897) Google Scholar The rates of liver dysfunction, acute kidney injury, and cardiac injury can be as high as 29%, 29% and 23%, respectively, in critically ill patients.6Yang 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 [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26].Lancet Respir Med. 2020; 8: 475-481https://doi.org/10.1016/S2213-2600(20)30079-5Abstract Full Text Full Text PDF PubMed Scopus (6897) Google Scholar From our analysis, our data demonstrate that cancer patients with prior COVID-19 infection who undergo ICI therapy do not show an overtly increased susceptibility to organ dysfunction in the short term. Although the quality of evidence is overall low, our study may help add important data to this emerging issue. Our study has several limitations, in addition to its retrospective nature. According to the COVID-19 Diagnostic Criteria,7National Health Commission of ChinaNew Coronavirus Pneumonia Prevention and Control Program.7th edn. 2020http://www.gov.cn/zhengce/zhengceku/2020-03/04/5486705/files/ae61004f930d47598711a0d4cbf874a9.pdfGoogle Scholar viral serum antibodies are indeed valid for diagnosis; however, false positives/negatives can still occur. Additionally, the number of such cases herein remains relatively small, and a larger sample size in patients with cancer is needed to validate these findings, including a deeper understanding regarding the diverse types of ICIs as well as the impact of combinatorial therapies. All other authors declare no competing interests. We thank all cancer patients and their caregivers involved in the study. None.