Demographic and clinical characteristics
In the 117 cancer patients with laboratory-confirmed COVID-19 infection who had been hospitalized at the two designated hospital as of March 12, 2020, 56 had received anti-cancer treatment, including surgery (16.2%), chemotherapy (19.7%), or radiotherapy (4.3%) as the most recent treatment in the last year and the other patients were cancer survivors in routine follow-up. The demographic and clinical parameters of the 117 patients are listed in Table 1. The median age was 63 years (interquartile range, 56 to 70). A total of 48.7% were male. Lung cancer was the most common type (25.6%); less common were digestive system cancer (23.9%), breast cancer (15.4%), thyroid cancer (8.5%), urinary system cancer (7.7%), gynecological tumor (6.8%), hematologic malignancies (6.8%), sarcoma (2.6%), head and neck cancer (0.9%) and cancer of unknown primary site (1.7%). Among the overall population, 48.7% had more than one coexisting illness, including diabetes (15.4%), hypertension (30.8%), cardiovascular disease (9.4%) and chronic obstructive pulmonary disease (COPD) (14.5%). Fever was present in 71.8% of the patients on admission. Less common symptom was cough (65.0%) and myalgia (50.4%); sputum production (39.3%), and diarrhea (14.5%) was uncommon.
Table 1
Clinicopathological characteristics of cancer patients infected with COVID-19.
Characteristics | All patients (n = 117) | Alive (n = 89) | Dead (n = 28) | P value |
Age (years) | | | | 0.499 |
< 60 | 41 (35.0) | 33 (37.1) | 8 (28.6) | |
≥ 60 | 76 (65.0) | 56 (62.9) | 20 (71.4) | |
Gender | | | | 0.029 |
Female | 60 (51.3) | 51 (57.3) | 9 (32.1) | |
Male | 57 (48.7) | 38 (42.7) | 19 (67.9) | |
Diagnosis (n [%]) | | | | |
Lung cancer | 30 (25.6) | 25 (28.1) | 5 (17.9) | 0.280 |
Breast cancer | 18 (15.4) | 16 (18.0) | 2 (7.1) | 0.166 |
Thyroid cancer | 10 (8.5) | 10 (11.2) | 0 (0) | 0.064 |
Digestive System Cancer* | 28 (23.9) | 20 (22.5) | 8 (28.6) | 0.509 |
Gynecological oncology# | 8 (6.8) | 8 (9.0) | 0 (0) | 0.100 |
Urinary system tumor& | 9 (7.7) | 4 (4.5) | 5 (17.9) | 0.021 |
Hematologic malignancies | 8 (6.8) | 2 (2.2) | 6 (21.4) | < 0.001 |
Sarcoma | 3 (2.6) | 1 (1.1) | 2 (7.1) | 0.079 |
Head and neck cancer | 1 (0.9) | 1 (1.1) | 0 (0) | 0.573 |
Unknown primary site | 2 (1.7) | 2 (2.2) | 0 (0) | 0.424 |
Comorbidities | | | | 0.955 |
Diabetes | 18 (15.4) | 13 (14.6) | 5 (17.9) | |
Hypertension | 36 (30.8) | 26 (29.2) | 10 (35.7) | |
Coronary heart disease | 11 (9.4) | 7 (7.9) | 4 (14.3) | |
COPD | 17 (14.5) | 12 (13.5) | 5 (17.9) | |
Symptom | | | | |
Dyspnea | 54 (46.2) | 32 (36.0) | 22 (78.6) | < 0.001 |
Cough | 76 (65.0) | 59 (66.3) | 17 (60.7) | 0.590 |
Expectoration | 46 (39.3) | 33 (37.1) | 13 (46.4) | 0.377 |
Malaise | 59 (50.4) | 45 (50.6) | 14 (50.0) | 0.959 |
Headache | 10 (8.5) | 6 (6.7) | 4 (14.3) | 0.213 |
Muscle ache | 10 (8.5) | 9 (10.1) | 1 (3.6) | 0.280 |
Pharyngodynia | 7 (6.0) | 7 (7.9) | 1 (3.6) | 0.432 |
Diarrhea | 17 (14.5) | 13 (14.6) | 4 (14.3) | 0.967 |
Fever | 84 (71.8) | 65 (73) | 19 (67.9) | 0.596 |
Annotation: *indicating 11 intestine cancer, 4 esophageal cancer, 6 liver tumor, 7 stomach cancer; #indicating 2 ovary cancer, 4 cervical cancer, 2 endometrial cancer; &indicating 5 bladder cancer patient, 2 prostate cancer, 2 renal cancer. |
28 (23.9%) cancer patients worsened and died of multiple organ failure, while 19 (16.2%) patients without a history of cancer died due to COVID-19 infection (Supplemental table 1). Male and the presence of dyspnea were more prevalent among patients died of COVID-19 than those alive (cancer patients p = 0.029, p < 0.001; non-cancer patients p = 0.006, p < 0.001). Moreover, patients with hematologic malignancy had the highest mortality than those with non-hematologic cancer (p < 0.001). However, age and comorbidities between the two groups were similar.
Laboratory findings
The laboratory findings on admission are shown in Table 2. Lymphocytopenia was present in 59.8% of cancer patients, thrombocytopenia in 17.9%, and leukocytosis in 13.7%. Most patients had increased levels of CRP; less frequent were increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), D-dimer. The alteration of laboratory testing (leukocytes, neutrophils, lymphocytes, thrombocytes, prothrombin time, activated partial thromboplastin time, CRP, procalcitonin, bilirubin and troponin) was associated with outcome of cancer patients diagnosed with COVID-19 (p = 0.023, p = 0.002, p = 0.027, p = 0.045, p < 0.001, p < 0.001, p < 0.001, p = 0.003, p = 0.005, p < 0.001). Besides, cancer patients had more prominent laboratory abnormalities than non-cancer patients (Supplemental table 2).
Table 2
Laboratory findings of cancer patients infected with COVID-19 on admission to hospital.
Characteristics | All patients (n = 117) | Alive (n = 89) | Dead (n = 28) | P value |
WBC, ⋅109/L | | | | |
< 4 | 24/117 (20.5) | 19/89 (21.3) | 5/28 (17.9) | 0.794 |
> 10 | 16/117 (13.7) | 8/89 (9.0) | 8/28 (28.6) | 0.023 |
Neutrophil count, ⋅109/L | 3.9 (2.6, 5.6) | 3.6 (2.5, 5.1) | 6.3 (2.9, 8.9) | 0.002 |
Lymphocytopenia | 70/117 (59.8) | 48/89 (53.9) | 22/28 (78.6) | 0.027 |
Thrombocytopenia | 21/117 (17.9) | 12/89 (13.5) | 9/28 (32.1) | 0.045 |
Prothrombin time, s | 13 (12, 14) | 13 (12, 14) | 15 (13, 16) | < 0.001 |
APTT, s | 36 (27, 42) | 33 (27, 41) | 41 (35, 49) | < 0.001 |
D-dimer, mg/L | 1.1 (0.5, 2.9) | 1.0 (0.5, 2.0) | 2.5 (1.1, 7.3) | 0.074 |
CRP | 36 (7, 92) | 26 (5, 56) | 96 (54, 145) | < 0.001 |
Procalcitonin | 0.09 (0.05, 0.26) | 0.06 (0.04, 0.15) | 0.39 (0.13, 1.07) | 0.003 |
Total bilirubin | 10.1 (6.7, 13.3) | 9.9 (6.4, 13.0) | 10.3 (8.3, 15.7) | 0.005 |
ALT > 40U/liter | 22/117 (18.8) | 19/89 (21.3) | 3/28 (10.7) | 0.274 |
AST > 40U/liter | 28/117 (23.9) | 19/89 (21.3) | 9/28 (32.1) | 0.310 |
Troponin, pg/mL | 1.9 (0, 4.4) | 1.9 (0, 2.5) | 15 (1.9, 61.8) | < 0.001 |
Annotation: Lymphocytopenia was defined as a lymphocyte count of less than 1000 per cubic millimeter. Thrombocytopenia was defined as a platelet count of less than 100,000 per cubic millime- ter. APTT indicates activated partial thromboplastin time. AST indicates aspartate aminotransferase |
Compared to alive patients, dead patients had increased levels of TNF-α, IL-2R, IL-6, IL-8, and IL-10 tested on admission (Fig. 1 and Supplemental Fig. 1). However, high level of TNF-α, IL-2R, IL-6, IL-8 did not raise the risk of death in non-cancer patients. Importantly, the levels of TNF-α, IL-2R, IL-6, IL-8, and IL-10 were significantly correlated with survival time of cancer patients with COVIP-19. These odds were further proved by logistic regression model after adjusting for other risk factors, including age, gender, cancer type, comorbidities, symptom and anti-cancer treatment (Table 3). In addition, T lymphocytes, B lymphocytes, T helper (Th) cells, and T suppressor (Ts) cells were diminished in cancer patients with a primary composite end-point event of death (Fig. 2). Cancer patients with more B cells and Th cells had longer survival than those with less B cells and Th cells (p = 0.007, p = 0.035). We further examined if the levels of cytokines were changed when cancer patients recovered from COVID-19. Figure 3 showed that IL-2R and IL-6 significantly decreased in the patients with better illness. These results strongly suggesting that the number of lymphocytes and cytokines could be used as independent prognostic factor predicting the outcome of cancer patients with COVID-19.
Table 3
Logistic regression analysis of survival of cancer patients tested for cytokines.
Characteristics | All patients | P value |
Age at diagnosis | 0.620 (0.179, 2.144) | 0.401 |
Gender | | 0.016 |
Female | 1 (Reference) | |
Male | 8.250 (1.044, 65.198) | |
Cancer type | | 0.006 |
Non-hematologic cancer | 1 (Reference) | |
Hematologic cancer | 5.380 (1.502, 19.269) | |
Comorbidities | | |
Diabetes | 1.343 (0.285, 6.328) | 0.687 |
Hypertension | 0.907 (0.234, 3.512) | 0.756 |
Coronary heart disease | 0.613 (0.150, 2.497) | 0.331 |
COPD | 1.254 (0.266, 5.907) | 0.865 |
Symptom | | |
Dyspnea | 11.556 (1.460, 91.474) | 0.004 |
Cough | 0.798 (0.169, 3.759) | 0.865 |
Expectoration | 4.855 (1.030, 22.898) | 0.020 |
Malaise | 1.365 (0.385, 4.840) | 0.654 |
Headache | 5.575 (0.455, 26.898) | 0.060 |
Muscle ache | 1.815 (0.230, 14.357) | 0.650 |
Pharyngodynia | 0.913 (0.116, 7.207) | 0.877 |
Diarrhea | 1.920 (0.542, 6.799) | 0.153 |
Fever | 2.179 (0.276, 17.202) | 0.445 |
Treatment | | |
No | 1 (Reference) | 0.020 |
Yes | 4.039 (1.043, 15.644) | |
Cytokines | | |
TNF-α | 4.510 (1.257, 21.259) | 0.031 |
IL-2R | 4.775 (1.012, 22.532) | 0.031 |
IL-6 | 6.566 (1.497, 15.062) | < 0.001 |
IL-8 | 4.811 (1.020, 22.687) | 0.031 |
IL-10 | 8.201 (1.736, 38.748) | 0.002 |
Treatments and outcomes
A majority of cancer patients (91.5%) received antivirus therapy, and 83.8% received intravenous antibiotic therapy; oxygen therapy was treated in 54.7% and mechanical ventilation in 28.1%; higher proportion of patients with critical disease received these therapies. Systemic glucocorticoids were given to 52 patients (44.4%).
Patients with non-hematologic cancer did not die rapidly compared to patients with hematologic cancer types (odds ratio [OR] 5.380, 95% CI 1.502–19.269; p = 0.006). Among patients with cancer, patients who underwent anti-cancer therapy in the past year had a markedly higher risk (33.3%) of death than did those not receiving therapy (15.0%) (OR 4.039, 95% CI 1.043–15.644; p = 0.020).