We evaluated the outcomes of cancer patients hospitalized for COVID-19 infection in Iran. The COVID-19 patients with a history of cancer had a significantly higher risk of severe outcomes than non-cancer patients. The excess risk of hospital death was higher in all cancer subsites than non-cancer patients. However, analyses among cancer patients showed that the excess risk was not statistically different, except for lung cancer, which had a statistically higher risk of 60-day mortality than other cancer patients. The risk of death was statistically higher in the incident patients with active disease and those with metastasis during the COVID-19 infection. In addition, males, old age, and low SO2 were significant predictors of COVID-19 death in cancer patients.
The previous meta-analysis based on 32 studies showed that the mortality rate of COVID-19 was higher in cancer patients (13.5%) compared to non-cancer patients (5.1%) (RR 1.66, 95% CI 1.33-2.07, P < .00001) [20]. Other studies from China and Italy confirmed that patients with different malignancies experienced a higher prevalence of COVID-19 infection and showed a higher mortality rate than other COVID-19 patients [21,22]. In China, the case fatality rate of cancer patients with COVID-19 infection was 28.6% and 20% [5,6,8] However, a study from Turkey reported a lower mortality rate and a CFR of 5.1% [20]. A recent systematic review of 57 studies showed that the summary relative risk of COVID-19 mortality in cancer patients compared to non-cancer patients was 1.44 (95% CI 1.19-1.76) [23]. Another systematic review showed that the relative risk of COVID-19 death in cancer patients was slightly higher in Asia (OR=2.92) compared to Europe (OR=2.37) and the US (OR=1.97) [24]. The case fatality rate in cancer patients was considerably higher in the current study (CFR=37%), and the OR of death in cancer patients compared to non-cancer patients reached 3.59. The extremely high mortality rate of cancer patients and the higher risk of death in these patients could be linked to the limited resource for managing COVID-19 patients. Although ICU admission was higher in cancer patients, it did not change the patient outcome.
Covid-19 patients with a history of hematologic malignancy experience a higher mortality rate compared to other cancers in China (41%-62%) (36), the USA (37%) [25], and the UK (36%) [20]. The COVID-19 Cancer Consortium (CCC19), an international collection of 120 institutions from the United States, European Union, Argentina, Canada, Mexico, and the United Kingdom, reported a mortality rate of 12% and 14% for solid and non-solid tumors [26]. The high mortality in hematological malignancies has been linked to intense immunosuppressive treatment [20] and higher susceptibility to viral infection in non-solid tumors [27]. In our study, the case fatality rate due to COVID-19 in non-solid tumors was slightly higher (41.7%) than in non-solid tumors (34.9%) overall. A significantly higher risk of lung cancer in this study supported the previous findings from China [28] [25], the USA, the UK [20], and Turkey [11]. Involvement of the upper aerodigestive system in head and neck cancer, upper GI tract, and lung cancers, and a high prevalence of metastasis (63.5%) during COVID-19 infection increased the risk of death among solid tumors in our cohort. Variable mortality rates among cancers in different studies [23,29] are associated with the designs of studies, type of cancer, study power, the prevalence of comorbidities, adjustment for confounding variables, access to standards of care [30], and recruitment of patients at various times and phases of the COVID-19 pandemic [31].
Comorbidities are associated with a poor prognosis in COVID-19 [32] In our cohort study, 57.3% of cancer patients had at least one comorbidity, including hypertension (31.38%), diabetes mellitus (23.8%), and heart disease (19.4%). However, after adjustment for confounding factors, we found no significant association between comorbidities and risk of Covid-19 death among cancer patients. Although limited studies supported our findings [33], most studies have shown an association between comorbidities and excess risk of severe outcomes [34].
Smoking has been associated with Covid-19 progression[35]. Although higher mortality was observed in thoracic cancers, the evidence on the risk of severe COVID-19 outcomes for other cancers is inconsistent. Although, we found no significant relationship between smoking and the risk of death due to Covid-19 in overall, non-solid tumors who were smokers were at a higher risk of death than non-smokers.
In this study, the cancer patients had significantly higher ICU admission and intubation than non-cancer patients. These results support previous findings that ICU admission was 45% higher in cancer patients than in non-cancer patients[36]. A systematic review and meta-analysis revealed that cancer patients had a two folds higher risk of adverse outcomes, including ICU admission than non-cancer patients [24]. So far, various ICU admission rates have been reported from around the globe [12], ranging from 7% to 19% [37–39] to 35% [40]. In our study, 35.8% of cancer patients were admitted to the ICU, which is relatively higher than previous findings. This high rate of ICU admission for our cancer patients could be associated with a high rate of metastasis in our patients and the notion of providing intensive care for cancer patients that were assumed to be the high-risk group for COVID-19 infection. Some studies with lower ICU admission rates reported that a greater number of their cancer patients met the inclusion criteria for ICU admission but could not allocate limited resources to all of them [37,41]. Research is needed to set priorities for ICU admission in cancer patients.
Strengths of this study include recruiting a large number of cancer patients and abstracting clinical data, including stage, cancer types, and treatment status. We also collected several confounding variables, including the oxygen saturation percentage, tobacco smoking history, and comorbidities. Analysis of 60-day mortality was an important addition to the existing evidence that emphasized the importance of follow-up care after the discharge from COVID-19 wards. The limitation of this study is that we did not collect laboratory tests reported as prognostic factors and signs of organ damage. Previous studies showed that inflammatory markers including neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin, and ferritin levels, lower albumin levels as well as creatinine, troponin I, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, high D-dimer and prolonged INR were associated with risk of death [11,28,42–45]
In conclusion, cancer patients have a high risk of hospital and 60-day mortalities due to COVID-19. Among all cancers, lung cancer patients have the highest risk of COVID-19 death. The prognosis of COVID-19 is poor for almost all cancer types patients, especially those under active treatment, metastatic, and those with a low SO2. Most cancer patients infected with COVID-19 require intensive care in the hospital. In addition, they should be monitored actively after their discharge from the hospital.