The major finding of this study was that the in-hospital mortality of SARS-CoV-2 and seasonal influenza was markedly increased when patients had cancer. In addition, the in-hospital mortality of SARS-CoV-2 patients was higher with and without cancer in comparison with the corresponding patient with seasonal influenza.
In total, we identified 7442 seasonal influenza and 29,284 COVID-19 cases. Although the observation time for COVID-19 lasted only one-and-a-half years, the number of cases was almost four times higher compared to seasonal influenza over a 5-year period. These findings are consistent with prior studies. It is assumed that the previous seasonal influenza infections lead to partial immunity and that the vaccination against influenza has an additional protective effect, although only 38% of all > 60 years old are vaccinated against influenza in Germany [1, 7, 8]. SARS-CoV-2 was able to hit an immunological naïve population worldwide, thus explaining the severity.
Recent studies showed that the SARS-CoV-2 vaccination that started in December 2020 had a positive impact on the hospital admission rate. This is especially seen when comparing the outcome of the first wave to the others [9, 10].
In comparing studies, hospitalized patients with seasonal influenza have been shown to have more comorbidities and be in tendency older, whereas COVID-19 patients were mainly men, younger with less comorbidities [1, 3, 8, 11, 12]. In our study, COVID-19 patients of the total cohort had a significant higher ECI than seasonal influenza patients, indicating a higher prevalence of comorbidities. This shift may be explained by the fact that previous studies examined mainly the first wave of COVID-19 (December 2019–May 2020). At the beginning of the pandemic, especially in Europe, people of younger/middle age were more affected due to travel and social gatherings, which was an initial accelerator for the pandemic . This changed toward the second surge, where outbreaks in nursing homes and long-term care facilities occurred regularly, leading to a higher median age of patients with more comorbidities. Among other reasons, this initial high infection rate is due to the susceptibility of an immunologically naïve population. Seasonal influenza vaccination, which is recommended for all person ages 60 years and older or with pre-existing conditions in Germany, may have had a protective effect in the elder age group leading to the lower median age in patients with seasonal influenza.
Cancer patients had an overall higher ECI in both COVID-19 and seasonal influenza cases compared to patients with these infections and no cancer. Recent studies addressing both infections showed that cancer patient had in general higher amount of comorbidities because of the cancer itself, its late onset and cancer-related morbidity [4, 14, 15]. In recent studies, diabetes, hypertension and obesity were among the most described comorbidities in both the general and cancer population, which is also seen in our study. Obesity and diabetes are generally known to cause a subtle chronic inflammation and an altered immune system, thus making these patients prone to a severe clinical course of infections [16, 17]. COVID-19 patients were more obese with diabetes presenting COVID-19-associated comorbidities, such as coagulopathy and pulmonary circulation disorders, compared to patients with seasonal influenza. Interestingly, we found in our study that seasonal influenza patients were affected significantly more often from chronic pulmonary disease than COVID-19 patients.
This is in line with previous reports where chronic pulmonary disease was more often found in patients tested positive for seasonal influenza. The fact that chronic respiratory disease is frequently observed in seasonal influenza patients, which have a less severe clinical outcome, supports the assumption of an intrinsic inflammation caused by SARS-CoV-2 leading to its more severe clinical evolution [1, 16,17,18].
Cancer patients with either one of the infections were older compared to the full cohort. These findings are consistent with studies that described an advanced median age for COVID-19 and seasonal influenza cases compared to the total cohort due to usual late onset of cancer [14, 15, 19, 20]. In the cancer cohort, we saw a male predominance regarding COVID-19 (58.2%) and seasonal influenza (56.1%). In the total cohort, the difference was not so distinct (52.1% vs 50.1%) which is in line with previously published studies .
Studies have already shown that COVID-19 in general has a severe outcome with high mortality of mechanically ventilated patients. Even though intensive care treatment and full life-support are widely available in Germany. Many patients, especially those with underlying conditions, died. Malignancies and its therapy can alter the immune system, making patients with cancer prone to a severe course of infections, especially COVID-19.
In our study, COVID-19 cancer patients were more likely to be admitted to the ICU than seasonal influenza patients. The available data for cancer patients with seasonal influenza regarding ICU admission are scarce. The ICU admission rate is described to be 17.6–22.8% in immunocompromised (including cancer) patients [5, 21]. This described COVID-19 ICU rate is consistent with a German-wide study from Rühthrich et al., but it varies widely between countries ranging from 7 to 19% [2, 14, 20, 22, 23]. Studies from Germany generally showed a higher ICU admission rate in cancer patients for COVID-19 compared with other countries, which is probably mainly due to higher ICU bed-capacity in Germany and thus less admission restriction [4, 24, 25]. This finding correlates with the higher mechanical ventilation rate observed in our COVID-19 cancer cohort. We have seen a lower mechanical ventilation rate (13.6%) in cancer patients affected with seasonal influenza than COVID-19 patients (17.2%) without statistical significance. Previous studies reported ventilation rates of COVID-19 patients ranging between 8 and 12% [2, 14, 22, 26, 27], which is lower than the rate that we detected in patients with COVD-19 and cancer. Throughout it is described that the COVID-19 ventilation rate is high with a range from 8 to 12%, but it remains lower than in our study.
In our study, SARS-CoV-2-positive patients had a remarkably higher in-hospital mortality than patients with seasonal influenza. The observed mortality of COVID-19 cancer patients was 34.9%, which is approximately two times higher compared to 17.9% for seasonal influenza, approximately three times higher than in non-cancer patients. This higher mortality in cancer COVID-19 patients is in accordance with other studies reporting a death rate of 21–33% [2, 4, 20, 28]. Especially patients with the diagnosis of lymphoma, including blood malignancies were at special risk of in-hospital mortality. This finding is in accordance to recent studies showing an increased risk due to alternated immune system making them more susceptible for severe course of infections .
Our mortality rate is found at the upper end of the published mortality range. A possible explanation could be the long observation time until August 2021. Early studies of the pandemic with a limited number of cases showed a general lower mortality with a study time of only a few months including only partially the second wave [8, 12, 25, 30]. Patients were younger in the early beginning of the pandemic with less comorbidities. In Germany, the mortality rate reached its peak in December 2020 , when elderly people living in long-term care facilities were affected. A declining mortality rate has been observed since then. The most recent studies examining the second and third wave of COVID-19 pandemic (when vaccination were not widely available) showed that the mortality and mechanical ventilation rate have declined and tend to be even lower than in seasonal influenza [32, 33].
Even though detailed studies are scarce, an explanation for this development probably is the vaccination programs, which prioritized the most vulnerable —elder— population first. Thus, the intermittent high mortality declined, thanks to public health programs and a better understanding of the disease and possible treatments. However, future studies will show if the mortality rate may be equal or even lower compared to seasonal influenza.
In summary, the increased mortality in the cancer cohort for both COVID-19 and seasonal influenza makes them a high-risk population. Public Health measurements need to address directly this patient group and take action to prevent an infection with either of these deadly diseases.
By promoting vaccination, especially with regard to the higher incidence of viral infection during the colder season, mortality might be reduced.