The COVID-19 pandemic has led to widespread global changes to patterns of patient management in multiple fields. Cancer patients have a highly susceptible immune system as a result of the cancer itself and its treatments (e.g., chemotherapy, radiotherapy, chemoradiotherapy) that they are undergoing. Individuals with cancer may be at higher risk for developing COVID-19 and have inferior outcomes compared with those without cancer.5,6 It could be suggested to postpone the anti-cancer treatment by the physicians after comprehensively considering the patients’ performance status, the severity of COVID-19, the urgency of treatment, and the intensity of therapy.2 Although the occasional postponed treatment may not lead to immediate disease progression, disruptions of health care would certainly be disadvantageous for long-term recurrence and mortality. Reliable evidence for safe resumption of intravenous anti-cancer therapy in post-COVID-19 patients is strongly warranted. The number of SARS-CoV-2 infections in China continues to rise since the release of the lockdown policy in December, 2022. We investigated the disease duration and immune responses of post- SARS-CoV-2 breast cancer patients, and evaluated the safety of resuming anti-cancer therapies.
Our data showed that the length of treatment delays was almost consistent with the SARS-CoV-2 nucleic acid conversion time, indicating a pandemic-related disruption in breast cancer treatment. The COVID-19 pandemic had a greater impact on older patients, with a significantly prolonged delayed time of treatment and increased likelihood of viral pneumonia. It is to be expected because the older were more likely to have comorbid conditions and weakened immune systems. Previous studies have demonstrated that older age and presence of comorbidities (e.g., diabetes, hypertension) were the main risk factors for severe and long COVID-19.6–8 The results suggested more intensive surveillance for older patients admitted with COVID-19 who have breast cancer.
In the current study, we demonstrated the decreased proportions of CD3 + CD4 + T cells, B cells, as well as CD3 + CD4+/CD3 + CD8 + ratio, suggesting a suppressed T cell-mediated immunity post-SARS-CoV-2 infection. In contrast, the cytokines including IL-6, IL-8, IFN-γ, etc., were broadly elevated in response to SARS-CoV-2 infection. Although the study lack of data on pre-SARS-CoV-2 infection, we collected the peripheral blood two months after recovery from SARS-CoV-2 infection, which should be considered closer to the baseline immune status pre-SARS-CoV-2 infection. It shows sharp decreased cytokines two months after recovery from SARS-CoV-2 infection (Figure S1). The results were consistent with the imbalanced host response to SARS-CoV-2, which was characterized by reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production.9 There might be a parallel between COVID-19 and cytokine release syndrome (CRS), with uniquely elevated IL-6 and IL1RA.9 Recombinant human granulocyte colony-stimulating factor (G-CSF) is widely given to patients to counteract neutropenia, which is commonly encountered after chemotherapy in breast cancer. It was reported that in the setting of active COVID-19 infection, G-CSF led to an increased number of hospitalizations and the need for high levels of oxygen supplementation and death.10 The rapidly increased neutrophils induced by G-CSF may cause the extensive infiltration of myeloid cells into the lungs, leading to a cytokine storm. Therefore, the potential risks versus benefits should be adequately considered before G-CSF administration in neutropenic cancer patients with COVID-19.
The pandemic-related disruptions in breast cancer care were demonstrated to have a small long-term cumulative influence on breast cancer mortality.4 Information on the safety of resuming anti-cancer therapies is required to identify the at-risk population, as well as to avoid unnecessary delays in cancer management. It has been reported that a high percentage of COVID-19 patients still showed mild-to-substantial residual radiological lung abnormalities three months after discharge.11 In our study, no severe adverse events or death occurred after the resumption of intravenous anti-cancer therapy, even in those showing viral pneumonia by CT scan. However, it is essential to evaluate the risk for each patient before resuming the anti-cancer therapy. Patients with older age, presented with comorbidities like hypertension, or treated with some molecular target drugs, might be at a higher risk of intensive care unit admission and/or death due to COVID-19 than people without these conditions.12,13 We propose the minimization of treatment delays and resumption of the anti-cancer therapy after adequately informing the patients of the risks and benefits. Novel health care managements such as tele-consultations and day-care services should be considered to provide optimal treatment strategies.
This is the first study investigating the immune responses and safety when resuming the intravenous anti-cancer therapy post-SARS-CoV-2 in breast cancer, which could provide an important guide for clinicians. There are several potential limitations of this study. First, this is a single-center retrospective study with limited samples. Second, the nucleic acid test was not conducted every day, so the nucleic acid conversion time could not represent the actual disease duration. Third, selection bias may exist given that analyses were based on patients attending medical care facilities. Fourth, this study lacked long-term dynamic monitoring of lymphocyte subsets and cytokines, especially before SARS-CoV-2 infection.