








key: cord-290712-flj352ql
authors: Bi, Jianping; Ma, Hong; Zhang, Dongsheng; Huang, Jing; Yang, Dongqin; Wang, Yajie; Verma, Vivek; Zhang, Tao; Hu, Desheng; Mei, Qi; Han, Guang; Li, Jian
title: Does Chemotherapy Reactivate SARS-CoV-2 in Cancer Patients Recovered from Prior COVID-19 Infection?
date: 2020-09-04
journal: Eur Respir J
DOI: 10.1183/13993003.02672-2020
sha: 
doc_id: 290712
cord_uid: flj352ql

Recovered COVID-19 cancer patients remain negative for SARS-CoV-2 after delivery of chemotherapy

To the Editor:

Cancer patients are particularly vulnerable to coronavirus disease 2019 (COVID-19) (1) (2) (3) . These individuals are not only more susceptible to this infection, but also more frequently develop severe pneumonia during the disease course (1) (2) (3) . One factor associated with an increasing risk for developing severe events in this population is oncologic therapy, especially cytotoxic chemotherapy. Therefore, some oncologists and societies recommend that chemotherapy should generally not be started until COVID-19 symptoms have completely resolved and viral testing becomes negative (3, 4) . Additionally, some cancer patients who have recovered from infection are recommended to withhold, postpone, or switch to alternative routes of chemotherapy (e.g. oral instead of intravenous [IV] infusion) until the end of the COVID-19 pandemic (3, 4) . LLHBCH2020LW-006).

The median age was 57 years (IQR: 46-63) and the median follow-up from initial administration of chemotherapy was 116 days (IQR: 100-125). Prior to chemotherapy administration, all patients were negative for SARS-CoV-2, and all had at least one positive result for anti-SARS-CoV-2 antibodies. In total, 5 (13%) patients were negative for immunoglobulin G (IgG -) and positive for immunoglobulin M (IgM + ), 30 (77%) were IgG + IgM -, and 4 (10%) were IgG + IgM + .

Among this cohort, lung cancer was the most frequent neoplasm (9 [23%] patients), followed by breast cancer (8 [21%] ) and colorectal cancer (7 [18%]). Fifteen (38%) patients had stage IV disease with distant organ metastasis. Twenty-seven (69%) patients had received chemotherapy prior to initially developing COVID-19, and 12 (31%) patients were chemotherapy-naïve. Thirty-three (85%) patients received multi-agent chemotherapy or a combination of chemotherapy and targeted therapies (including 5 patients with intravenous chemotherapy plus a PD-1 inhibitor); 6 (15%) received either orally administered drugs or a combination of targeted drug therapies (Table 1) .

At the time of last follow-up, all patients remained negative for SARS-CoV-2, without suspicious changes on chest CT. Twenty-two (56%) patients experienced altered immunoglobulin test results; specifically, twelve (31%) patients who were initially IgG + IgMbecame IgG -IgMafter the median 57 days (IQR: 36-66) from initial administration of chemotherapy. Among the four (10%) patients who were initially IgG + IgM + , three patients became IgG -IgM + , and one became IgG + IgMrespectively after 54, 65, 101, and 23 days of chemotherapy. Two (5%) patients who was initially IgG + IgMbecame IgG + IgM + after 55, 72 days of chemotherapy. Three patients who was initially IgG -IgM + became IgG -IgMafter 59, 94 and 101 days of chemotherapy and only one patient initially IgG -IgM + became IgG + IgM -.

Treatments were tolerated well in this cohort. At least one therapy-associated adverse event was registered in 31 (79%) patients and all adverse events were of grades I or II, except for four cases of grade III-IV neutropenia which returned to normal after treatment with Granulocyte colony-stimulating factor (G-CSF).

Potential re-emergence of COVID-19 in recovered patients receiving immunosuppressive chemotherapy is a major oncologic and public health concern.

Concerns of reactivation of a prior infection are not limited to COVID-19. Previous studies have shown that reactivation of hepatitis B virus (HBV) occurs in nearly 20% of cancer patients undergoing chemotherapy, and may result in varying degrees of liver damage (6, 7) . There has also been a report that chemotherapy may cause reactivation of tuberculosis (8) . Additionally, many studies have illustrated (in the recovered COVID-19 population) that chemotherapy is associated with a higher risk of developing severe events (e.g. pneumonitis), as compared to cancer patients without receipt of recent chemotherapy (1, 2). However, not all studies have supported such conclusions; some have found no significant effect on mortality for patients having undergone chemotherapy within the prior four weeks (9, 10) . Those studies mainly addressed whether chemotherapy could predict for hospitalization, severe disease, and mortality in cancer patients with COVID-19 infection. However, limited information is known about the outcome of chemotherapy for cancer patients with prior COVID-19 infection. To address this knowledge gap, this study's findings suggest that administering chemotherapy to this population is associated with a very low short-term risk of SARS-CoV-2 reactivation. Further work is required to prospectively follow these subjects in the longer term.

Many studies have indicated that patients with COVID-19 have varying degrees of multiple organ dysfunction (11) (12) (13) , especially those who are critically ill (13) . The rate of liver dysfunction, acute kidney injury, and cardiac injury were as high as 29%, 29% and 23%, respectively (13) . To date, it is unknown whether chemotherapy would make cancer patients with prior COVID-19 infection more vulnerable to organ damage. Although our data demonstrate that this population does not demonstrate an overtly increased susceptibility to organ dysfunction in the short term, corroboration with longer-term prospective data is required for firmer conclusions.

Our study has several limitations. First, according to the updated COVID-19

Diagnostic Criteria (7th Edition) (14) , viral serum antibody-based tests are indeed valid for diagnosis; however, false positive and false negative test results can occur.

The sensitivity and specificity of the colloidal gold immunoassay utilized herein for IgG, IgM, and IgG/IgM was 83%/74%/84% and 99%/97%/95%, respectively (15) .

Second, the number of cases in this study is relatively small, and retrospective assessment can never exclude biases in patient selection. Third, the duration of follow-up in this study was relatively short and it may take a longer period of time to determine immune-related alterations caused by chemotherapy in cancer patients who have recovered from COVID-19 infection. Nevertheless, when conservatively interpreted, our study indicates no overt short-term increase in the risk for SARS-CoV-2 reactivation following immunosuppressive chemotherapy in this uniquely vulnerable population.

To our knowledge, this is the first study reporting that recovered COVID-19 cancer patients remain negative in the short-term for SARS-CoV-2 after delivery of chemotherapy. The knowledge/experience gained from this study may aid guidelines on delivering chemotherapy to cancer patients recovered from COVID-19 infection during this pandemic as well as to address potential "second waves" in the future. 

Cancer patients in SARS-CoV-2 infection: A nationwide analysis in China

Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan

A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: An International Collaborative Group

COVID-19) Resources for the Cancer Care Community

Positive RT-PCR Test Results in Patients Recovered From COVID-19

Frequency of Hepatitis B Virus Reactivation in Cancer Patients Undergoing Cytotoxic Chemotherapy: A Prospective Study of 626 Patients With Identification of Risk Factors

Hepatitis B Reactivation in Patients Receiving Cytotoxic Chemotherapy: Diagnosis and Management

Reactivation of pulmonary tuberculosis during cancer treatment

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study

COVID-19 and Liver Dysfunction: A Systematic Review and Meta-Analysis of Retrospective Studies

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)

Mar 27;e201017

Clinical Course and Outcomes of Critically Ill Patients With SARS-CoV-2 Pneumonia in Wuhan, China: A Single-Centered, Retrospective, Observational Study

New coronavirus pneumonia prevention and control program

Diagnostic efficacy of anti-SARS-CoV-2

IgG/IgM test for COVID-19: A meta-analysis

We thank Tian Tang (Renmin Hospital of Wuhan University, Wuhan, Hubei, China) for her assistance in the study and we thank all patients involved in the study.

All other authors declare no competing interests.

All authors had full access to all the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. 

