key: cord-0949200-d3269bbp authors: Donnino, M. W.; Moskowitz, A.; Thompson, G. S.; Heydrick, S. J.; Pawar, R. D.; Berg, K. M.; Mehta, S.; Patel, P. V.; Grossestreuer, A. v. title: Comparison Between Influenza and COVID-19 at a Tertiary Care Center date: 2020-08-22 journal: nan DOI: 10.1101/2020.08.19.20163857 sha: 49297a6217ddc3ac15d1d11209f889cce130c8f4 doc_id: 949200 cord_uid: d3269bbp ABSTRACT Background: Widespread reports suggest the characteristics and disease course of coronavirus disease 2019 (COVID-19) and influenza differ, yet detailed comparisons of their clinical manifestations are lacking. Objective: Comparison of the epidemiology and clinical characteristics of COVID-19 patients with those of influenza patients in previous seasons at the same hospital Design: Admission rates, clinical measurements, and clinical outcomes from confirmed COVID-19 cases between March 1 and April 30, 2020 were compared with those from confirmed influenza cases in the previous five influenza seasons (8 months each) beginning September 1, 2014. Setting: Large tertiary care teaching hospital in Boston, Massachusetts Participants: Laboratory-confirmed COVID-19 and influenza inpatients Measurements: Patient demographics and medical history, mortality, incidence and duration of mechanical ventilation, incidences of vasopressor support and renal replacement therapy, hospital and intensive care admissions. Results: Data was abstracted from medical records of 1052 influenza patients and 583 COVID-19 patients. An average of 210 hospital admissions for influenza occurred per 8-month season compared to 583 COVID-19 admissions over two months. The median weekly number of COVID-19 patients requiring mechanical ventilation was 17 (IQR: 4, 34) compared to a weekly median of 1 (IQR: 0, 2) influenza patient (p=0.001). COVID-19 patients were significantly more likely to require mechanical ventilation (31% vs 8%), and had significantly higher mortality (20% vs. 3%; p<0.001 for all). Relatively more COVID-19 patients on mechanical ventilation lacked pre-existing conditions compared with mechanically ventilated influenza patients (25% vs 4%, p<0.001). Limitation: This is a single-center study which could limit generalization. Conclusion: COVID-19 resulted in more hospitalizations, higher morbidity, and higher mortality than influenza at the same hospital. COVID-19 and influenza are both highly infectious viral diseases characterized by pneumonia and acute respiratory failure in severe cases. Both place a burden on the health care system, but objective granular assessments of their comparative impact on individuals and the healthcare system are lacking in the literature. The epidemiology, symptomology and annual public health burden presented by influenza is generally well characterized; however, this is largely through estimates as opposed to comprehensive reporting. 1 The Centers for Disease Control and Prevention (CDC) estimates that over the past 10 years, between 9 and 45 million people have contracted influenza annually in the United States, with annual hospitalizations ranging from 140,000 -810,000 and annual mortality ranging from 12,000 to 61,000 (between 0.10% and 0.17% of all cases), depending on the severity of the season. 2 Influenza generally achieves community spread nationwide and can strike all age groups, but mortality is consistently higher in patients who are elderly, immunocompromised, and/or have pre-existing comorbidities such as chronic obstructive pulmonary disease, chronic kidney injury, cirrhosis, or cardiac disease. [3] [4] [5] [6] [7] [8] [9] Decades of experience with influenza have led to vaccination programs which can mitigate the impact of influenza in years when the predominant circulating strain is accurately predicted. 10 Official CDC counts indicate that over one million people in the United States have contracted COVID-19 between the virus's first detected cases through April 30, 2020, with over outcomes of those patients without comorbid disease, frequency of non-pulmonary organ injury, and mortality are lacking, yet essential for understanding these two disease processes. In this study, we compared the epidemiology and clinical characteristics of COVID-19 patients admitted to a large tertiary care teaching hospital in March and April of 2020 with those of influenza patients admitted to the same hospital over the prior five years. Design: This was a single center, retrospective study at an urban tertiary care center. We compared patients admitted to the hospital with influenza during five influenza seasons (September-April 2014-2019) to patients admitted to the hospital with COVID-19 in March and April 2020. This study was reviewed by the Institutional Review Board at Beth Israel Deaconess Medical Center, which determined the study met exempt status. Written informed consent was therefore not required. Patient Population: Adult (aged >17 years) patients were included if they were admitted to the hospital for confirmed influenza or COVID-19 during the time frames of interest. Patients with influenza or COVID-19 were identified by ICD-10 codes (see appendix) and/or laboratorybased testing. Laboratory diagnosis of influenza and COVID-19 were carried out through specific real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays of nasal swab specimens. COVID-19 or influenza diagnosis for all subjects identified by ICD-10 codes were manually reviewed for confirmation. The ICD-10 codes are displayed in supplement Table S1 . Study Data Abstraction: Study data was abstracted from patient electronic medical records based on the mechanism for identification of subjects described above. Data included All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . demographics, personal medical histories (e.g. chronic comorbid conditions), laboratory findings on admission, intensive care unit admission status, intensive care unit length of stay, mechanical ventilation, hospital length of stay, and mortality. Key variables including presence and duration of mechanical ventilation and mortality were manually reviewed to verify the data. To compute volume of admissions between the two diseases, weekly counts of hospital admissions and mechanically ventilated patients were assessed during the peak two months of influenza seasons from 2014-2019 and from March-April 2020 for COVID-19. Reasons for intubation were manually categorized and all past medical history was manually extracted. All cases for which laboratory testing occurred greater than five days after admission were reviewed to determine if disease was believed to be nosocomial. For other variables (e.g., laboratory values), a sample of randomly chosen data was verified using manual chart review. Definitions for elements of the data abstraction are displayed in supplement Table S2 . Data Analysis: Continuous data are presented as medians with interquartile ranges and categorical data are presented as counts and percentages. For continuous outcomes (duration of mechanical ventilation, duration of index hospital stay, number of weekly admissions, number of weekly incident mechanical ventilations), medians were compared using a Wilcoxon ranksum test. For categorical outcomes (incidence of mechanical ventilation, incidence of shock, incidence of renal replacement therapy, hospital readmissions, ICU admissions, in-hospital mortality, reason for mechanical ventilation, and proportion of patients on mechanical ventilation with no major comorbidities), proportions were compared using chi-squared or Fisher's exact tests, as appropriate. All analyses were done using Stata 14.2 (College Station, TX) and a pvalue <0.05 was considered statistically significant. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . In total, 1855 patients were identified and 1635 were included in the study ( Figure 1 ). Of these, 583 patients had laboratory-confirmed COVID-19 and 1052 patients had laboratoryconfirmed influenza. An overview of admissions, intensive care unit admissions, receipt of mechanical ventilation, and mortality is illustrated per influenza season compared to COVID-19 (Table 1 ). The total admissions for influenza per eight-month influenza season averaged 210 compared to a total of 583 COVID-19 admissions over the two month COVID-19 study period. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . Patient demographics and medical history are summarized in Table 2 Table 3 . Overall, the reasons for intubation in COVID-19 patients were different than those intubated for influenza (p<0.001). Pneumonia and/or acute respiratory distress syndrome (ARDS) was the reason for 94% of intubations in COVID-19 patients, while this accounted for only 56% of intubations in influenza patients. Additionally, no COVID-19 patients received mechanical ventilation due to exacerbation of preexisting conditions compared to 14% of influenza cases who received mechanical ventilation for this indication. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . https://doi.org/10.1101/2020.08.19.20163857 doi: medRxiv preprint Table 4 COVID-19 has been compared to influenza by both health care professionals and the lay public 12-16 but limited detailed objective data are available for comparing and contrasting the impact of these two disease processes on patients and hospitals. We found that admissions for COVID-19 over a two month period at our medical center were more than double the total All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . https://doi.org/10.1101/2020.08.19.20163857 doi: medRxiv preprint number of admissions for influenza during any 8-month influenza season in the past five years. In addition to the larger volume of cases within a much shorter time period, severity of illness and lethality for COVID-19 were also markedly higher than for influenza. We observed more mechanically ventilated COVID-19 patients (i.e., those with severe, life-threatening illness) in a two month period than occurred in five entire seasons of influenza combined, and a similar observation was made with patient deaths. Taken together, these findings indicate that COVID-19 causes more severe disease and is more lethal than influenza. Other studies aimed at total incidence (hospitalized plus non-hospitalized) suggest a higher rate of spread (Ro) of COVID-19 than influenza [17] [18] [19] In this specific subgroup, five patients with COVID-19 died in the two-month period compared to one with influenza over five years. Pneumonia and acute respiratory distress syndrome were the predominant causes of mechanical ventilation for COVID-19 (94%), whereas this was not the case for influenza (55%). With influenza, the need for mechanical ventilation often developed as a result of exacerbation of a pre-existing health condition such as asthma or chronic obstructive pulmonary disease (COPD), which did not occur in COVID-19. The apparently higher rate of pneumonia and ARDS in our COVID-19 cohort may at least partly All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . https://doi.org/10.1101/2020.08.19.20163857 doi: medRxiv preprint explain the more frequent occurrence of respiratory failure and death even in the absence of serious comorbidities. In addition to acute respiratory failure, rates of vasopressor and renal replacement therapy were significantly increased in COVID-19 compared to influenza. The increased disease severity reflected in the rates of acute respiratory failure and other-organ injury paralleled the overall higher lethality of COVID-19 which resulted in 119 deaths in 2 months compared to 34 deaths from influenza over five seasons. The disparity in deaths was driven by both increased volume of cases and increased lethality within that volume in COVID-19 patients. This study did not evaluate organ-injury such as liver failure, neurological injury, and coagulation disorders, all of which have been reported with COVID-19. [20] [21] [22] [23] [24] [25] [26] The increase in volume of COVID-19 cases compared to influenza is noted in Figure 2 . This increase in patient volume occurred despite the implementation of increasingly stringent social distancing in Boston starting on March 15, 2020 27 and a statewide stay-at-home advisory starting on March 24, 2020. 28 New cases began to decrease approximately 6 weeks after these measures were taken. Thus, the overall volume of cases of COVID-19 in this report was likely modified by these measures, whereas these mitigation measures were not taken during any influenza season. Influenza, however, can be modified by the implementation of widespread vaccination programs which are currently not available for COVID-19. While not a focus of this study, the critical care resources required to manage the marked increase and severity of disease in COVID19 included the emergent conversion of surgical and cardiac intensive care units to medical intensive care units, and the conversion of postanesthesia care units and multiple medical wards to intensive care units. The conversion of any such space to an intensive care unit has not been done for any influenza season. In addition to space conversion, human resources (i.e., staffing models for new intensive care units), personal protective equipment, and increased use of dialysis were all part of the hospital-wide response (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . Figure 2 . Comparison of COVID-19 hospital admissions during the 9 weeks in March-April 2020 and Influenza hospital admissions for the peak 9 weeks in five different seasons. The arrow denotes the approximate timing of the "Stay at Home" advisory put in place in Massachusetts on March 24, 2020. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . Alcohol Use Disorder: n (%) 33 (6) 147 (14) 16 (9) 7 (8) Tobacco: n (%) 107 (18) 211 (20) 29 (17) 22 (26) *BMIs were missing from 77 patients with COVID-19 and 22 patients with influenza All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . (6) 1 (1) 2 (1) 2 (1) 1 (1) 0 (0) 0 (0) 1 (1) 3 (2) 17 (30) 4 (5) 8 (10) 1 (1) 2 (2) 1 (1) 1 (1) 0 (0) All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 22, 2020. . https://doi.org/10.1101/2020.08.19.20163857 doi: medRxiv preprint Assessment of Deaths From COVID-19 and From Seasonal Influenza United States Department of Health and Human Services, Center for Disease Control. Past Seasons Estimated Influenza Disease Burden Influenza virus-related critical illness: pathophysiology and epidemiology. Crit Care Influenza in patients with cancer after 2009 pandemic AH1N1: An 8-year followup study in Mexico. 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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted