Although the NCCN guideline recommends withholding antitumor therapy for 10–20 days in tumor patients infected with COVID-19 [8], there is not much evidence-based information about when antitumor therapy can be resumed in these patients, especially now that the low toxicity and highly transmissible omicron has become the dominant strain.

In the current study, we retrospectively collected clinical information from tumor patients with COVID-19 who were treated at our center between December 2022 and June 2023 to analyze the safety of resuming antitumor therapy early after SARS-CoV-2 nucleic acid tests turned negative. Most of the patients received antitumor therapy within 7 days after the SARS-CoV-2 nucleic acid test turned negative, and about half of the patients received antitumor therapy within 3 days. None of the patients died of antitumor therapy related AEs. The incidence of grade 3–4 AEs was acceptable. To better study the impact of COVID-19 infection on the safety of antitumor therapy, we selected patients who had received antitumor therapy prior to infection with COVID-19 from the current cohort as a self-control cohort and compared the incidence of AEs between the two cohorts. The results showed that antitumor therapy after experiencing COVID-19 infection did not increase the incidence or severity of AEs compared to receiving antitumor therapy before COVID-19 infection. However, our study showed that the incidence rates of increased alanine aminotransferase (26.3% vs. 20.9%, p = 0.0003) and aspartate aminotransferase (28.9% vs. 18.6%, p < 0.0001) were higher before they were infected with COVID-19. Nevertheless, the paired comparison of the same patient before and after COVID-19 infection did not show a statistical difference. This may be due to the small sample size.

Previous studies have reported that antitumor therapy, especially chemotherapy, causes immune deficiencies in patients with malignant tumors, resulting in prolonged clearance of replication-competent viruses (> 20 days) [10]. Patients who received chemotherapy within one month of COVID-19 infection had a higher risk of clinically serious events than those who did not receive chemotherapy [1]. Therefore, the NCCN guideline recommends that oncology patients with COVID-19 withhold antitumor treatment for 10–20 days, depending on the patient’s severity and subsequent antitumor regimens. A previous study indicated that restart antitumor therapy in breast cancer patients 2–4 weeks after mild or moderate COVID-19 infection did not increased treatment-related adverse events [6]. However, in the current study, most tumor patients received antitumor therapy within a week, and half of the patients received antitumor therapy within 3 days after SARS-CoV-2 turned negative, and the incidence or severity of AEs did not increase. It should be pointed out that 23.2% of the patients in our study did not hold antitumor therapy when they were infected, and no increased incidence of AEs was observed in these patients. Among these patients, four received targeted therapy, two received targeted therapy + chemotherapy, three received targeted therapy + immunotherapy, and one received targeted therapy + immunotherapy + chemotherapy. Based on this, we questioned whether it is necessary to withhold antitumor therapy during the period when omicrons are the predominant strains, especially in patients receiving only targeted therapy and immunotherapy rather than chemotherapy.

In addition to antitumor therapy-related AEs, another issue of concern is whether resuming antitumor therapy shortly after SARS-CoV-2 turned negative can cause COVID-19 re-infection because immunity would be impaired by antitumor therapy. In this study, re-infection with COVID-19 only occurred in two patients. A previous study reported that re-positive COVID-19 tests occurred in 2.4%–69.2% of recovered COVID-19 patients[11]. The inconsistency between our results and previous reports may be due to the fact that omicron had became the predominant strain at the time of data collection for this study, and it is highly likely that most of the included patients were infected with omicron, which is highly infectious but has less toxicity than any previous strains.

In addition to antitumor therapy-related AEs, we recorded the clinical manifestations of COVID-19 in tumor patients. We found that most of our patients had mild infections, and approximately one-fourth of them were asymptomatic. Most of the patients’ symptoms relieved within a week. The results are inconsistent with previous reports that oncology patients are more likely to develop severe infections [1, 12]. Interestingly, we noticed that the clinical manifestations of the non-tumor population (physicians and nurses) infected with COVID-19 in the same period in the same ward were more symptomatic. The main symptoms included high fever, sore throat, muscle aches, headache, loss of appetite, and diarrhea, and the duration of symptoms was longer [13]. This suggests that mild symptoms in tumor patients may be associated with a different immune response to the SARS-CoV-2 strain between tumor patients and non-tumor individuals, rather than the low toxicity of the strain. The severity of COVID-19 may be related to the immune response of the body to the virus [14]. Previous studies have indicated that individuals with severe COVID-19 have higher levels of neutralizing antibodies than those with mild disease or asymptomatic infections [15, 16]. Patients with tumors have impaired immune function to some extent, and may have a weaker immune response to viruses, producing lower levels of antibodies and a weaker inflammatory response, resulting in milder symptoms [17, 18]. However, mild symptoms do not mean mild disease. Impaired immune function may lead to decreased viral clearance and prolonged viral clearance time, thus increasing the risk of transition to severe disease [10]. Therefore, we propose that in patients with tumors or other immunocompromised populations, immunity should be increased after infection with COVID-19 to shorten the time to viral clearance. However, in individuals with severe COVID-19 (not with tumors or other infections), appropriate suppression of immune function may be helpful in reducing symptoms after the clearance of the virus (negative nucleic acid test).

In this study, a retrospective analysis of COVID-19-infected tumor patients found that resuming antitumor therapy shortly after nucleic acid tests turned negative did not increase antitumor therapy-related AEs or the incidence of COVID-19 re-infection. Resuming antitumor therapy early after SARS-CoV-2 test turned negative may be safe. In addition, we suggest that in immune-compromised populations, immunity should be strengthened during COVID-9 infection to shorten the time to viral clearance, and in immune-competent populations, appropriate suppression of immune function after viral clearance may help reduce symptoms. However, some limitations of this study should be noted. First, this study was a retrospective analysis and may have had some recall bias. Second, the patients included in this study were all from the same center, and the clinical presentation may have been influenced by the prevalent strains in the region and differed from those in other regions. Finally, the sample size of this study was small, and more prospective clinical studies are needed to validate the results of this study further.