SARS-CoV-2-Induced Remission of Chemotherapy Resistance B-Cell Non-Hodgkin Lymphoma: A Case Report

It is reported that virus may induces cross-reactive immune response against host normal tissue or tumor [1, 2]. The summary of these cases may provide new light on the immunotherapy of tumors.

A 65-year-old woman was diagnosed with B-cell non-Hodgkin lymphoma (stage IVB) in December 2018. Figure 1a shows the increased FDG-PET/CT lymph node uptake. After diagnosis, she received two courses of chemotherapy (R-CHOP), with no significant remission. Then, she received another two more courses of R-CHOP chemotherapy. The treatment did not prevent tumor progression (online suppl. Fig. 1; for all online suppl. material, see https://doi.org/10.1159/000541964). Since March 2019, she started receiving ibrutinib, a Bruton’s tyrosine kinase inhibitor, and achieved partial remission. According to the NCCN Guidelines, ibrutinib is the second-line therapy for relapsed/refractory lymphoma [3]. She continued ibrutinib treatment for more than 3 years. However, lymph node enlargement persisted (online suppl. Fig. 2).

As the patient is not eligible for vaccination, she was not vaccinated for the COVID-19. On December 23, 2022, the patient was diagnosed with SARS-CoV-2 pneumonia based on a PCR test and CT image (online suppl. Fig. 3). She was admitted to our hospital and administered hydrocortisone for inflammation. PET-CT examination on January 5, 2023 showed the remission of pneumonia (online suppl. Fig. 4) and, surprisingly, widespread resolution of lymphadenopathy and reduced metabolic uptake on PET-CT (Fig. 1b).

Three months later, the CT image examined on April 10, 2023 showed recovery from COVID-19 and continued complete remission of lymphoma (online suppl. Fig. 5). The SARS-CoV-2 PCR test showed a negative result. One and a half years later, the CT image examined on June 13, 2024 showed continued complete remission of lymphoma (online suppl. Fig. 6).

This case report provided inspirational messages for antitumor immunotherapy. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material. We hypothesize that SARS-CoV-2 infection was probably the cause of lymphoma remission in this patient. SARS-CoV-2 infection triggered an antitumor immune response. Previous reports also showed that SARS-CoV-2 infection induced the remission of Hodgkin lymphoma [1], and other infections induced the remission of diffuse large B-cell lymphoma [4]. The cross-reactivity between virus-specific T cells and tumor antigens is considered the underlying mechanism. There is report showing that lymphopenia is correlated with the severity COVID-19 [5]. Although the lymphocyte account of this patient is also lower than normal value (1.1–3.2 × 10⁹/L), her lymphocyte account increased following SARS-COV-2 infection (online suppl. Table 1), which partially support the hypothesis that infection induced immune cross-reactivity. Although it has been reported that hydrocortisone may contribute to the remission of lymphoma [6], we argue that this is not the case for this patient, as hydrocortisone had also been included in her previous chemotherapies. Mapping epitope characteristics on B cell non-Hodgkin lymphoma antigen and SARS-CoV-2 antigen may provide much-needed information for antigen-based antitumor immune therapy in the future. Further investigation into the relationship between genetic polymorphisms of HLA and antigenic cross-reactivity will provide more insights into antigen-based antitumor strategies.

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Beijing Gobroad Boren Hospital (Approval No. 2000040665). Written informed consent was obtained from the patient for publication of this case report and all accompanying images.

There was no conflict of interest declared.

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Yan Xiao wrote the manuscript, Jinwei Wang, Kai Yang, and Meiling Jiang collected and analyzed the data, and Bo Zhang reviewed and edited the manuscript.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from [Y.X.] upon reasonable request.