COVID-19

Clinical Outcomes of Cancer Patients with COVID-19 Infections

People who are being treated for cancer may be at increased risk of severe COVID-19, and clinical outcomes of COVID-19 are generally worse in people with cancer than in people without cancer. An analysis of nearly 50,000 patients with COVID-19 showed that all-cause mortality was higher in patients with cancer, and that patients with cancer were more likely to be admitted to intensive care units.

Retrospective studies suggest that patients with cancer who were admitted to the hospital with SARS-CoV-2 infection have a high case-fatality rate, with higher rates observed in patients with hematologic malignancies than in those with solid tumors.

Patients with cancer who are receiving chemotherapy are at risk of developing neutropenia. A retrospective study suggests that patients with cancer and neutropenia have a higher mortality rate if they develop COVID-19. Studies have reported an increased risk of poor clinical outcomes for patients with COVID-19 in the setting of neutropenia and/or during the perioperative period.

In a study that used data from the COVID-19 and Cancer Consortium Registry, patients with cancer who were in remission or who had no evidence of disease had a lower risk of death from COVID-19 than those who were receiving active treatment. However, it is unclear whether cancer survivors have an increased risk for severe COVID-19 and its complications when compared with people without a history of cancer.

COVID-19 Treatment in Cancer Patients

The recommendations for treating COVID-19 in patients with cancer are the same as those for the general population. Patients with cancer are at high risk of progressing to severe COVID-19 and are eligible to receive anti-SARS-CoV-2 therapies in the outpatient setting if they develop mild to moderate COVID-19.

In patients with COVID-19 who required supplemental oxygen or mechanical ventilation, the use of dexamethasone has been associated with lower mortality than standard of care treatment alone. Tocilizumab or baricitinib used in combination with dexamethasone is recommended for some patients with severe or critical COVID-19 who exhibit rapid respiratory decompensation.

Antiviral Therapy Considerations

The use of antiviral or immune-based therapies to treat COVID-19 can present additional challenges in patients with cancer. Clinicians should pay careful attention to potential overlapping toxicities and drug-drug interactions between drugs that are used to treat COVID-19 and cancer-directed therapies, prophylactic antimicrobials, and other medications.

A 5-day course of ritonavir-boosted nirmatrelvir (Paxlovid) is one of the preferred therapies for treating mild to moderate COVID-19 in nonhospitalized patients who are at risk for disease progression. However, this regimen has the potential for significant and complex drug-drug interactions with concomitant medications, primarily due to the ritonavir component of the combination.

Boosting with ritonavir, a strong cytochrome P450 (CYP) 3A inhibitor, is required to increase the exposure of nirmatrelvir to a concentration that is effective against SARS-CoV-2. Ritonavir may also increase concentrations of certain concomitant medications, including certain chemotherapeutic agents and immunotherapies used to treat cancer. Significant increases in the concentrations of these drugs may lead to serious and sometimes life-threatening drug toxicities.

Cancer Therapies After COVID-19 Infection

Decisions about administering cancer-directed therapy to patients with acute COVID-19 and those who are recovering from COVID-19 should be made on a case-by-case basis; clinicians should consider the indication for chemotherapy, the goals of care, and the patient’s history of tolerance to the treatment.

Prolonged SARS-CoV-2 Shedding in Immunocompromised Patients

Prolonged shedding of SARS-CoV-2 virus has been reported in patients who are immunocompromised. A systematic review found that replication-competent virus could be detected for a median of 20 days in these patients, compared to 11 days in the general population. Prolonged viral shedding may affect SARS-CoV-2 testing strategies and isolation durations for this group of patients.

Based on a large cohort study* conducted at MSKCC, patients with B-cell lymphomas were at particularly high risk for persistent SARS-CoV-2 positivity (an indicator of continued viral shedding).

• Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19–infected patients with lymphoma.
• Conversely, B cell–depleting therapy was the primary driver of re-hospitalization for COVID-19.
• Relapsed or refractory lymphoma and recent systemic therapy were independent predictors of hospital readmission for symptomatic COVID-19, the strongest individual treatments of which were anti-CD20 therapy and bendamustine.

Taken together, these data indicate that immunosuppression, particularly loss of B-cell and CD4 T-cell immunity driven at least in part by B cell–directed therapies, is a risk factor for persistent symptomatic COVID-19 infection and suggests that CD4⁺ T-cell and/or B-cell function may contribute to complete viral eradication. Consistent with this hypothesis, patients who were ultimately rehospitalized for COVID-19 exhibited an increased proportion of activated CD4⁺ and CD8⁺ T cells, suggesting ongoing active infection in these patients.

The unique contribution of this report is the description of persistent symptomatic COVID-19 in patients with lymphoid malignancy, a condition predisposed by previous anti-CD20 therapy and observed in 21% of anti-CD20–treated patients in our cohort. The syndrome manifests as a chronic protracted illness marked by slowly progressive or relapsing respiratory illness with progressive lower airway changes on CT imaging and persistent viral RNA detection.

*Lee CY, Shah MK, Hoyos D, et al. Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies. Cancer Discov. 2022;12(1):62-73.

SARS-CoV-2 Evolution in Immunocompromised Hosts

In addition to the substantial direct morbidity from COVID-19 and interruption in cancer care, chronic persistent SARS-CoV-2 infection poses the additional threat of extended transmissibility and selection pressure that could generate immune-evading mutations. Intra-host evolution in chronic SARS-CoV-2 infection has led to the detection of mutations found in variants of concern, raising intense speculation that immunocompromised patients may serve as reservoirs for the emergence of critical mutations in the receptor binding domain region of the virus.

In the study conducted at MSKCC*, for patients with persistent SARS-CoV-2 positivity:

• High levels of viral entropy consistent with intra-host viral evolution were observed, particularly in patients with impaired CD8⁺ T-cell immunity
• There was no indication of reinfection or co-infection in any of the analyzed samples.
• Our analysis points to immune dysregulation characterized by combined loss of B-cell function and impaired CD4⁺ T-cell counts (CD4 <100 cells/μL) and compensatory innate immune and CD8⁺ T-cell activation as the basis for this chronic syndrome.

These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population.

*Lee CY, Shah MK, Hoyos D, et al. Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies. Cancer Discov. 2022;12(1):62-73.