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Patients with cancer are considered at risk for COVID-19, but in some cases, could the infection be a good thing? A case report of a patient with Hodgkin lymphoma whose condition went into remission led to a headline suggesting that COVID -19 had “cured” the patient.
The case report was published in the British Journal of Haematology.
The patient subsequently experienced relapsed, but the SARS-CoV-2 infection had induced remission for some time.
In the case report, Sarah Challenor, MD, and David Tucker, MD, both of the Department of Haematology, Royal Cornwall NHS Hospital Trust, Truro, Cornwall, United Kingdom, describe how a 61-year-old man was referred to their department with progressive lymphadenopathy and weight loss. He had been receiving hemodialysis for end-stage renal failure secondary to IgA nephropathy and had not been taking immunosuppressive therapy for 3 years after a failed renal transplant.
The patient was diagnosed with Epstein-Barr virus (EBV)–positive classical Hodgkin lymphoma. Fluorodeoxyglucose positron-emission tomography/CT (FDG-PET/CT) revealed that he had stage IIIs disease.
Soon after his diagnosis of Hodgkin lymphoma, he developed respiratory symptoms and was diagnosed with polymerase chain reaction (PCR)–positive SARS-CoV-2 pneumonia.
“This patient’s lymphoma was diagnosed about this time last year (February 2020),” Tucker told Medscape Medical News. He has “PET avid and clinically palpable Hodgkin lymphoma.”
In March–April 2020, he was admitted to the hospital with COVID-19. The patient remained in the hospital for 11 days. He received supportive care on a regular medical unit but was not treated with corticosteroids or immunotherapy. He was then discharged home.
Four months later (May 2020), scans and tests revealed that his multiple tumors had largely vanished. The palpable lymphadenopathy had shrunk, and an interim PET/CT scan showed that lymphadenopathy had largely resolved. The EBV viral load on PCR had declined from 4800 copies/mL (log10, 3.68) to 413 copies/mL (log10, 2.62).
The patient’s condition had gone into remission.
Coincidence or COVID-19 Induced?
The authors hypothesize that the SARS-CoV-2 infection triggered an antitumor immune response. “The putative mechanisms of action include cross-reactivity of pathogen-specific T cells with tumor antigens and natural killer cell activation by inflammatory cytokines produced in response to infection,” they write.
They point to a 2012 case report in which a patient with diffuse large B-cell lymphoma (DLBCL) experienced spontaneous regression of disease in the maxillary sinus after infection with concurrent pneumonia and Clostridium difficile colitis. The authors of that case report note that spontaneous DLBCL remission has been reported, and in some cases, it occurred the setting of concurrent infection.
Tucker explained that the mechanism of action remains unclear. “I have not seen spontaneous remission of classical Hodgkin lymphoma before, although it does rarely occur, so I think coincidence is less likely,” he said. “The coincidence seemed worthy of note, so we wrote it up.”
He speculates that there may have been some sort of immune response, “possibly T-cell mediated or perhaps related to interferon-induced cell destruction, as we know that interferon can control lymphoma ― it was used as maintenance therapy until it was replaced by rituximab,” he said. “What I do know is that he received no medications such as steroids or other cytotoxics which could explain the response.”
However, the remission was only temporary. “His disease returned in August 2020, and he has subsequently been successfully treated,” said Tucker. “So it was only a transient response, but relapse was not present at the time of writing [the case report].”
Two experts weighed in on the report.
“I would have wanted to check the diagnosis of lymphoma ― but with that impressive PET, it certainly seems a reasonable diagnosis,” commented Girish Venkataraman, MBBS, associate professor of pathology at the University of Chicago, Chicago, Illinois.
Infection with a virus “does turn on the immune microenvironment quite a bit, and depending on the host baseline immune competence, it does seem tenable that the cytokine profile/signature of the microenvironment was altered enough by the SARS-CoV-2 infection that rendered the microenvironment to be not conducive for the growth of the lymphoma cells,” he said.
“Hodgkin disease is very dependent on an immunosuppressive anergic microevironment to thrive and subvert any immune response,” he noted.
This phenomena has been described before, and the hypothesis is plausible, commented Leo I. Gordon, MD, FACP, professor of medicine and codirector of the Hematologic Malignancies Program, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
“Given the very encouraging data with checkpoint inhibitors, which activate T cells, in classical Hodgkin lymphoma, the idea that activated T cells might lead to remission is not far-fetched and is consistent with what we think is a mechanism of lung injury in SARs-CoV-2 ― namely, overenthusiastic T cells,” he said. “A caveat is that we have seen spontaneous remissions in this disease, especially in those patients who have EBV-associated classic Hodgkin lymphoma, so the role that [infection] plays in this case remains unclear.
“While no one is advocating a SARS-CoV-2 infection as a treatment for lymphoma, this highlights the importance of understanding the common immunologic mechanisms at play,” he said.
The authors, Venkataraman, and Gordon have disclosed no relevant financial relationships.
Br J Haematol. Published online January 2, 2021. Full text
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