COVID-19 is regularly compared to influenza. Mortality and case-fatality rates vary widely depending on incidence of COVID-19 and the testing policy in affected countries. To date, data comparing hospitalized patients with COVID-19 and influenza is scarce.
Data from patients with COVID-19 were compared to patients infected with influenza A (InfA) and B (InfB) virus during the 2017/18 and 2018/19 seasons. All patients were ≥ 18 years old, had PCR-confirmed infection and needed hospital treatment. Demographic data, medical history, length-of-stay (LOS), complications including in-hospital mortality were analyzed.
In total, 142 patients with COVID-19 were compared to 266 patients with InfA and 300 with InfB. Differences in median age (COVID-19 70.5 years vs InfA 70 years and InfB 77 years, p < 0.001) and laboratory results were observed. COVID-19 patients had fewer comorbidities, but complications (respiratory insufficiency, pneumonia, acute kidney injury, acute heart failure and death) occurred more frequently.
Median length-of-stay (LOS) was longer in COVID-19 patients (12 days vs InfA 7 days vs. InfB 7 days, p < 0.001). There was a fourfold higher in-hospital mortality in COVID-19 patients (23.2%) when compared with InfA (5.6%) or InfB (4.7%; p < 0.001).
In hospitalized patients, COVID-19 is associated with longer LOS, a higher number of complications and higher in-hospital mortality compared to influenza, even in a population with fewer co-morbidities. This data, a high reproduction number and limited treatment options, alongside excess mortality during the SARS-CoV-2 pandemic, support the containment strategies implemented by most authorities.
As of July 26th 2020, the ongoing SARS-CoV-2 pandemic has infected over 68 million people and has caused over 1,560,000 deaths worldwide , challenging affected countries and healthcare systems. The pandemic has impacted the lives of billions on multiple levels and has had a major impact on the world economy .
Influenza viruses are highly contagious and during seasonal epidemics excess mortality is observed. While therapeutic options and vaccinations exist for influenza vaccination rollout for COVID-19 is still limited and delayed by supply problems, and whilst there is growing evidence that certain drugs may be effective, these are still deemed to have limited therapeutic effect [3,4,5,6,7,8,9,10]. In comparison to COVID-19 there are no strict regulations and containment strategies during seasonal influenza virus epidemics.
While mortality and case-fatality-rates of COVID-19 seem to be higher than for influenza A (InfA) and influenza B (InfB), reliable information is difficult to obtain due to asymptomatic and oligosymptomatic presentations in both cases. Asymptomatic cases are described in 18–75% for SARS-CoV-2 [11, 12]) and 4–85% for influenza . Case-fatality rate estimates range from 0.25 to 5.7% for COVID-19 [14, 15] and from 0.1 to 1% for influenza .
Here we compare the demographic data, medical history, length-of-stay (LOS), complications including ICU admission and in-hospital mortality between hospitalized PCR confirmed patients with COVID-19, InfA and InfB. Treatment and isolation were performed at the same department by the same specialists for infectious diseases, ensuring equal quality of medical care.
Study design and data gathering
This study was conducted at the Department for Infectious Diseases and Tropical Medicine at the Kaiser-Franz-Josef Hospital in Vienna, Austria. We compared demographics, medical history, laboratory results, LOS and complications including ICU admission and in-hospital mortality of patients with polymerase chain reaction (PCR)-proven COVID-19, InfA and InfB virus infections.
Data from COVID-19 patients were collected from March 1st to April 25th 2020. PCR testing for SARS-CoV-2 took place at our hospital’s laboratory institute or at other certified laboratories in Vienna. Data from all subsequent influenza patients were collected retrospectively in 2017/18 and prospectively in 2018/19. Influenza diagnosis was made at the emergency department before admission using the Alere™ i Influenza A & B assay (Alere, Waltham, MA, USA) in 2017/18 and the Cobas® Liat® point-of-care test (POCT) from Roche (Roche Molecular Systems, Pleasanton, CA, USA) in 2018/19.
All hospitalized patients ≥ 18 years with molecular proven COVID-19 or influenza were eligible for the study. Patients’ medical history, laboratory parameters and complications were collected via a standardized form during hospital admission. Incomplete data were updated retrospectively from patients’ electronic health records whenever possible.
The study was approved by the local ethics committee.
Definition of variables
The first day of any COVID-19 or influenza-associated symptom was considered to be disease onset. Fever was defined as a body temperature ≥ 38 °C. Dehydration was defined as the need for intravenous fluids based on clinical appearance. Respiratory insufficiency was defined as SpO2 ≤ 93% at room air or the need for supplementary oxygen based on clinical judgment by the treating physician. Pneumonia was defined as typical consolidation and/or opacity on a radiological image. Myositis was defined as a creatine-kinase (CK) level above 1000 U/L. Heart failure was defined by new onset or worsening of peripheral edema and/or congestion on X-ray in patients with history of chronic heart failure and without any other cause. Acute kidney injury was defined as either an increase of creatinine level by 0.3 mg/dl from the baseline kidney function within 48 h or an increase of ≥ 1.5 times the baseline (presumed to have occurred within the previous 7 days due to the current episode of illness). When no previous creatinine level was available as baseline, the acute kidney injury was assessed retrospectively. We did not differentiate between complications which were present on admission or developed during admission.
Data were double-checked, entered in a MS Excel sheet (Microsoft, Redmond, WA, USA) and anonymized before statistical analysis. The statistical analyses were performed with SAS V9.4 and R Version4.0.2. Categorical variables were described by counts and percentages. For metric non-normally distributed variables the median (Md) and interquartile range (IQR) were used. Significance tests for categorical variables were made via cross tables and Chi-squared test or Fisher’s exact test, where applicable. Kruskal–Wallis tests were performed to compare the three groups (InfA, InfB and COVID-19) for metric non-normally distributed variables. A two-sided alpha < 0.05 was considered statistically significant.
To check for difference in binary outcomes (e.g. acute heart failure, in-hospital mortality) logistic regression analyses were performed with the factor group (InfA, InfB vs COVID-19). Odds ratios and two-sided 95% confidence intervals reported.
For in-hospital mortality and discharged alive from hospital analysis, competing risk analysis was performed and the cumulative incidence curves were compared using Gray’s test (Gray 1988).
Patients demographics and medical history
The total population consisted of 708 patients, 142 (20.1%) had COVID-19, 266 (37.6%) InfA and 300 (42.3%) InfB. 356 (50.3%) were male, with a higher proportion of male patients in the COVID-19 group. Overall median age was 73.5 years (61–82) and varied between groups (p < 0.001); overall InfB patients were oldest.
Differences in medical history were demonstrated between the groups, with lower rates of chronic kidney disease (p < 0.001) and chronic obstructive disease (p = 0.002) in the COVID-19 group. Median time from symptom onset to hospitalization was 7 days (IQR 3–10) in the COVID-19 group and differed significantly from InfA (2 days; IQR 1–4) and InfB (2 days; IQR 0.8–4) positive patients (p < 0.001). Antiviral treatment differed significantly between groups (p < 0.001), while antibiotic prescription rates did not yield a statistical significance (p = 0.11). For details see Table 1.
(n = 708)
(n = 142)
(n = 266)
(n = 300)
|Age (years)a||73.5 (61–82)||70.5 (53–80)||70 (58–80)||77 (67–85)||< 0.001|
|Sex (male)||356/708 (50.3%)||84 (59.2%)||131 (49.3%)||141 (47%)||0.053|
|BMI (kg/m2)||25.6 (22.7–30.1) [n = 488]b||25.9 (24.2) [n = 75]||25.3 (22.2–29.7) [n = 218]||26 (23–30.5) [n = 195]||0.246|
|Time from symptom onset to hospitalization||3 days (1–5) n = 616||7 days (3–10) n = 126||2 days (1–4) n = 244||2 days (0.8–4) n = 246||< 0.001|
|Antiviral treatment||433 (61.1%)||67 (47.2%)c||188 (70.7%)d||178 (59.3%)d||< 0.001|
|Antibiotic treatment||282 (39.8%)||46 (32.4%)||114 (42.9%)||122 (40.7%)||0.112|
|Chronic kidney disease||212 (29.9%)||26 (18 .3%)||75 (28.2%)||111 (37%)||< 0.001|
|Obstructive pulmonary disease||194 (27.4%)||23 (16.2%)||92 (34.6%)||79 (26.3%)||< 0.001|
|Diabetes||176 (24.9)||27 (19%)||69 (25.9%)||80 (26.7%)||0.193|
|Atrial fibrillation||133 (18.8%)||30 (21.1%)||46 (17.3%)||57 (19%)||0.635|
|Coronary heart disease||48/312 (15.4%)||20/142(14.1%)||28/170 (16.5%)||NA||0.56|
|Any malignancy||94 (13.3%)||12 (8.5%)||31 (11.7%)||51 (17%)||0.029|
|Dementia||82 (11.6%)||12 (8.5%)||30 (11.3%)||40 (13.3%)||0.142|
|Congestive heart failure||75 (10.6%)||17 (12%)||28 (10.5%)||30 (10%)||0.82|
|Peripheral artery disease||45/707 (6.4%)||7/141 (5%)||14 (5.3%)||24 (8%)||0.309|
|Rheumatic disease||11/312 (3.5%)||6 (4.2%)||5/170 (2.9%)||NA||0.54|