Patient characteristics
A total of 235 patients were referred to our hospital with COVID-19 between January 31, 2020 and May 25, 2020. We retrospectively enrolled 32 patients with a history of cancer. They were all Asians except for one Australian. A total of 11 patients (34%) eventually died, and all deaths were due to COVID-19. Twenty-one patients (66%) were discharged or transferred with negative RT-PCR results.
Table 1 shows the clinical characteristics of these patients. The median age was 74.5 (range, 24–90) years and 22 patients (69%) were men. A total of 25 patients (78%) had solid tumors, while 7 (22%) had hematologic malignancies. In addition to cancer, 19 (59%) had at least one comorbidity, with hypertension being the most common (13 patients, 41%). Thirteen patients (41%) received cancer treatment within 30 days.
CT or X-ray on admission showed radiological features of pneumonia in 27 patients (84%). Lymphocytopenia (lymphocyte count <0.8×109 /L) occurred in 13 patients (41%) and was predominant among the non-survivors (73% vs. 24%). Twenty-two patients (69%) received favipiravir, while ten patients (31%) were treated with systematic glucocorticoids.
The median time from illness onset to admission was 7 days (interquartile range [IQR], 4–8). The median time from illness onset to death was 24 days (IQR, 15–26). The median period between illness onset and the first effective negative SARS-CoV-2 RT-PCR result was 22 days (IQR, 18–25) in survivors.
Risk factors for mortality
The results of univariate analysis for OS are shown in Table 2. The following risk factors were significantly associated with mortality: lymphocyte count, albumin, LDH, serum ferritin, and CRP on admission. In our study, age, comorbidities, D-dimer, and cancer status were not associated with OS. The Kaplan-Meier survival curve stratified by high and low lymphocyte count is shown in Figure 1A (30-day OS: 90% and 46%, P=0.004). We further stratified patients with high and low lymphocyte count by comorbidities (30-day OS: 100%, 82%, 80%, and 25%, P=0.003, for high lymphocyte count and no comorbidities, high lymphocyte count and some comorbidities, low lymphocyte count and no comorbidities, and low lymphocyte count and some comorbidities) (Figure 1B).
We suspected that the reduction in lymphocyte count was possibly caused by a certain factor, such as hematological toxicity of recent cytotoxic chemotherapy. Hence, we stratified patients with low lymphocyte count by whether they developed COVID-19 within the rest periods of cytotoxic chemotherapy or not. There was no significant difference between patients within the rest periods and other patients (30-day OS: 44% and 50%, P=0.75) (Figure 1C).
Outcomes in patients with active cancer
The clinical characteristics of 17 patients with active cancer are summarized in Supplementary Table 1. Seven patients received chemotherapy, while two patients received ICIs (nivolumab and pembrolizumab + ipilimumab) within 30 days before the onset of COVID-19. Four patients received continuous hormone therapy. Pembrolizumab treatment was discontinued in one patient with metastatic lung cancer more than 200 days before the onset of COVID-19. One patient experienced a relapse with liver metastases after remission induced by repeated chemotherapy and surgery for rectal cancer. Two patients had not been treated yet as they developed COVID-19 before cancer treatment.
Figure 2 shows the timeline of cancer treatment, illness onset, SARS-CoV-2 RNA detection, and death in this subgroup of patients. The longest period between illness onset and the first effective negative SARS-CoV-2 RT PCR result was 56 days in a patient who received bendamustine plus rituximab (BR) for Waldenström’s macroglobulinemia/lymphoplasmacytic lymphoma. Moreover, another patient who received BR for mantle cell lymphoma 17 days before the illness onset tested positive for the virus at 42 days after the onset and eventually died. One patient who received azacytidine for acute myeloid leukemia (AML) 10 days before the onset and showed severe pancytopenia at the onset progressed rapidly and died in one week. One patient with ALK-negative anaplastic large cell lymphoma (ALCL) who received brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisolone (A+CHP) 7 days prior to the onset of COVID-19 also died within 26 days. Among the four COVID-19 patients with hematological malignancy who developed COVID-19 within the rest periods of chemotherapy, three died and the other one had the longest duration of viral shedding among survivors. The two patients with AML and acute lymphocytic leukemia (ALL) had received induction and consolidation therapy, respectively. They both recovered from pancytopenia, remained in remission at the onset of COVID-19, and were eventually cured.
Two patients receiving ICIs within 30 days eventually improved and were discharged, although one of them had elevated CRP and ferritin levels on admission and was treated with high-flow nasal cannula oxygen therapy without glucocorticoid therapy.