Lymphocyte may be a reference index of the outcome of cancer patients with COVID-19

Demographic and clinical characteristics

In the 117 cancer patients with laboratory-confirmed COVID-19 who had been hospitalized at the two designated hospitals as of March 12, 2020. 56 had received anti-cancer treatments, including surgery (16.2%), chemotherapy (19.7%), and radiotherapy (4.3%) as the most recent treatment in the last year and the others were cancer survivors in routine follow-up. The demographic and clinical parameters of the 117 cancer 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 these patients on admission. Less common symptoms were cough (65.0%), myalgia (50.4%), and sputum production (39.3%); diarrhea (14.5%) was uncommon.

28 (23.9%) cancer patients with COVID-19 worsened and died of multiple organ failure, while 19 (16.2%) patients without a history of cancer died due to COVID-19 (Supplementary Table 1). Male and the presence of dyspnea were more prevalent among all the patients who died of COVID-19 than those alive (cancer patients p=0.029, p<0.001; non-cancer patients p=0.006, p<0.001; respectively). Moreover, oncological 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 cancer patients had increased level of C-reactive protein (CRP); less frequent were increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), D-dimer. The alteration of laboratory blood tests (leukocytes, neutrophils, lymphocytes, thrombocytes, prothrombin time, activated partial thromboplastin time, CRP, procalcitonin, bilirubin and troponin) were associated with outcome of cancer patients 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; respectively). Besides, cancer patients had more prominent laboratory abnormalities than non-cancer patients (Supplementary Table 2).

Compared to those alive, all the patients who died from COVID-19 had increased levels of TNF-α, IL-2R, IL-6, IL-8, and IL-10 tested on admission (Figure 1 and Supplementary Figure 1). However, high levels of TNF- α, IL-2R, IL-6, and 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 COVID-19. These odds were further proved by logistic regression model after adjusting for other risk factors, including age, gender, cancer type, comorbidities, symptoms, and anti-cancer treatments (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 (Figure 2). Cancer patients with more B cells and Th cells had longer survival time than those with less B cells and Th cells (p=0.007, p=0.035; respectively). 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 cancer patients with better illness. These results strongly suggesting that the number of lymphocytes and cytokines could be used as independent prognostic factors to predict the outcome of cancer patients with COVID-19.

Treatments and outcomes

Most cancer patients with COVID-19 (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 cancer patients with COVID-19, those who underwent anti-cancer therapies in the past year had a markedly higher risk (33.3%) of death than did those not receiving anti-cancer therapies (15.0%) (OR 4.039, 95% CI 1.043-15.644; p=0.020).

Patients

In this retrospective, two-center study, we reviewed the medical records of all patients with laboratory-confirmed COVID-19 and cancer history who were hospitalized in Tongji hospital of Tongji Medical College, Huazhong University of Science and Technology and Renmin Hospital of Wuhan University. The admission date of these patients was from Jan 14, 2020 to March 12, 2020. Following the WHO interim guidance, COVID-19 was diagnosed by real-time quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) assay or high-throughput sequencing of pharyngeal swab specimens. Nucleic acid confirmation of COVID-19 was conducted at the Chinese Center for Disease Prevention and Control until January 23, 2020, and subsequently in the two designated hospitals in Wuhan, China. Only nucleic acid-confirmed patients were incorporated into the analysis.

We extracted the clinical symptoms, comorbidities, and laboratory findings from electronic medical records. All the patients were followed up to April 20, 2020. If additional information or clarification was required, data were obtained directly from attending doctors or other health care providers. For each patient, the symptoms during their hospitalization were documented in the present study, including fever, cough, expectoration, fatigue, diarrhea, etc. Fever was defined as axillary temperature more than 37.5° C. All laboratory assessments were carried out depending on our institutional guidelines and clinical conditions of the patients. Laboratory testing included whole blood count, blood chemistry, coagulation test, lymphocyte subpopulation, and measures of procalcitonin, C-reactive protein (CRP), and serum cytokines. The primary composite end-point was death. The study was granted approval by the ethical committee of our institute with a waiver of written informed consent for emerging infectious diseases.

Statistical analysis

Continuous variables were shown as median and compared by the Mann-Whitney U test; categorical variables were summarized as number (%) and compared by χ2 test or Fisher’s exact test between different groups. Scatter plots were drawn to describe lymphocyte subpopulation and plasma cytokine concentrations. The Kaplan-Meier method was utilized to measure the correlation of cytokines and lymphocytes with survival, and the Cox proportion hazard analysis was utilized to clarify potentially significant differences in outcome. A two-sided p value of less than 0.05 was considered significant for all applied statistical test. All the analyses were calculated with the use of R language, version 3.6.3 (http://www.r-project.org/).

Ethics approval and consent to participate

The study is approved by the ethical committee of Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology with a waiver of written informed consent for emerging infectious diseases.

Availability of data and materials

The authors confirm that the data supporting the findings of this study are available within the article (and/or) its supplementary materials.