COVID‐19 in cancer patients may be presented by atypical symptoms and higher mortality rate, a case‐controlled study from Iran

Abstract Background Coronavirus disease 2019 (COVID‐19) pandemic imposes serious problems to health systems around the world and its rapid expansion makes it difficult to serve patients with certain health conditions such as cancer patients which might be at high risk for mortality if they are infected by the severe acute respiratory syndrome coronavirus 2. Aim To compare the outcomes of cancer patients admitted due to COVID‐19 and compare them with data of COVID‐19 infected patients without a history of cancer. Methods In this case‐controlled study, 93 healthy people and 92 patients with malignancy admitted for COVID‐19 were enrolled. The clinical features and laboratory indicators were assessed at the presentation and both groups were followed‐up for treatment options and outcomes prospectively and compared at the level of P ≤ .05. Results COVID‐19 related mortality rate in malignant patients was significantly higher than patients without malignancy (41.3% vs 17.2%, P = .0001). The risk of death increased significantly in patients with malignancy (OR = 8.4, P = .007) and mechanical ventilation (OR = 3.3, P = .034) independent of other variables. Fever (64.5% vs 43.5%, P = .004), chill (35.5% vs 14.1%, P = .001), malaise (49.5% and 30.4%, P = .008), dry cough (51.6% vs 26.1%, P = .0001), and vomiting (17.2% vs 5.4%, P = .012) were reported significantly lower in cancer patients. Conclusion The results suggest that cancer patients who were infected by COVID‐19 may present with atypical symptoms are at higher risk of mortality independent of the demographic data, comorbidities, and treatments.

who showed that the mortality rates of COVID-19 infected patients with and without malignancy was 23.9% and 1.5%, respectively; using Also, the duration of admission was the same (medians; 8 vs 6.5 days, P-value = .155). Table 1 shows characteristics of COVID-19 infected patients with and without malignancy in detail.
As shown in Table 2 Regression analysis showed that the risk of death increased significantly in patients with malignancy (OR = 8.4, P = .007) and mechanical ventilation (OR = 3.3, P-value = .034) independent of other variables (Table 3).
Subsequently, the stepwise binary logistic regression was performed in COVID-19 infected patients with cancer to define the predisposing factors of death. However, no factor can predict the outcome including the type of malignancy, stage of the disease, and recent oncologic treatment (chemotherapy or radiotherapy, data not presented).

| DISCUSSION
This study aimed to assess the clinical features, laboratory values, treatment options, and outcomes of cancer patients admitted due to COVID-19 and compare them with data of COVID-19 infected patients without a history of cancer. Our results showed that mortality was significantly higher in cancer patients infected by COVID-19, although the comorbidities especially diabetes mellitus were more prevalent in non-malignant patients. Moreover, the probability of positive PCR for CODIV-19 was significantly higher in non-malignant patients. Regression analysis showed that the risk of death in COVID-19 infected patients with malignancy was about nine times more than other patients. Also, the patients who needed mechanical ventilation had a significantly higher mortality rate. An overview of recent data on COVID-19 and its impact on patients with malignancies has been provided in Table 4.
As stated earlier, there are limited data on the potential interaction of COVID-19 and malignancy and its treatments, and this specific category of COVID-19 infected patients accounts for a small portion of patients in the recent studies. 14,15,20 However, studies from China, Europe, and the United States proposed the predisposing role of malignancy on the increased mortality rate of COVID-19 with higher rates for patients with active cancer receiving the anti-cancer treatments. 4,7,19,21 Although, there is not a general agreement in this context with lower mortality rates in cancer patients with COVID-19. 6,17 Our study showed that cancer patients might present less with typical symptoms of COVID-19 and COVID-19 infected patients with malignancy reported a lower frequency of fever and dry cough comparing previous studies. 5,18 However, studies are confirming our results regarding obscuring the main presentation of COVID-19 in cancer patients. 22 Also, the rate of neutropenia, anemia, and thrombocytopenia which mainly had been the side-effects of chemotherapy was higher in our study as expected. Besides, pleural effusion and lymphadenopathy were reported significantly higher in patients with malignancy that we believed is related to the underlying malignant condition.
Our study has some limitations. Due to limited resources during the first peak of pandemic and special economic conditions of Iran, it was not possible to do PCR tests for all patients and therefore, we had to enroll patients only based on pulmonary symptoms and radiography. Also, our analyses were based on patients with symptomatic cancer admitted to COVID-19 specific treatment centers of Mashhad, and patients who managed in an outpatient setting or were asymptomatic were not included. Therefore, the cohort might not be entirely representative of all patients with cancer. Patients on an end-of-life care pathway would be unlikely to be included in the current study.

| CONCLUSION
The results suggest that cancer patients who were infected by COVID-19 are at higher risk of mortality independent of the demographic data, comorbidities, and treatments. Also, the false-negative rate of PCR may be higher in COVID-19 infected patients with malignancy and they might present with atypical presentation leading to delay diagnosis, collectively.

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest to be reported.

ETHICAL STATEMENT
The protocol of the study was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.REC.1399.059) and a written informed consent form was obtained from the patients or the legal guardian.

DATA AVAILABILITY STATEMENT
All data generated and analyzed during this study can be accessible through direct communication with corresponding author and agreement of all research team members.