Lancet: COVID far deadlier than influenza

Background

To date, influenza epidemics have been considered suitable for use as a model for the COVID-19 epidemic, given that they are respiratory diseases with similar modes of transmission. However, data directly comparing the two diseases are scarce.

Methods

We did a nationwide retrospective cohort study using the French national administrative database (PMSI), which includes discharge summaries for all hospital admissions in France. All patients hospitalised for COVID-19 from March 1 to April 30, 2020, and all patients hospitalised for influenza between Dec 1, 2018, and Feb 28, 2019, were included. The diagnosis of COVID-19 (International Classification of Diseases [10th edition] codes U07.10, U07.11, U07.12, U07.14, or U07.15) or influenza (J09, J10, or J11) comprised primary, related, or associated diagnosis. Comparisons of risk factors, clinical characteristics, and outcomes between patients hospitalised for COVID-19 and influenza were done, with data also stratified by age group.

Findings

89 530 patients with COVID-19 and 45 819 patients with influenza were hospitalised in France during the respective study periods. The median age of patients was 68 years (IQR 52–82) for COVID-19 and 71 years (34–84) for influenza. Patients with COVID-19 were more frequently obese or overweight, and more frequently had diabetes, hypertension, and dyslipidaemia than patients with influenza, whereas those with influenza more frequently had heart failure, chronic respiratory disease, cirrhosis, and deficiency anaemia. Patients admitted to hospital with COVID-19 more frequently developed acute respiratory failure, pulmonary embolism, septic shock, or haemorrhagic stroke than patients with influenza, but less frequently developed myocardial infarction or atrial fibrillation. In-hospital mortality was higher in patients with COVID-19 than in patients with influenza (15 104 [16·9%] of 89 530 vs 2640 [5·8%] of 45 819), with a relative risk of death of 2·9 (95% CI 2·8–3·0) and an age-standardised mortality ratio of 2·82. Of the patients hospitalised, the proportion of paediatric patients (<18 years) was smaller for COVID-19 than for influenza (1227 [1·4%] vs 8942 [19·5%]), but a larger proportion of patients younger than 5 years needed intensive care support for COVID-19 than for influenza (14 [2·3%] of 613 vs 65 [0·9%] of 6973). In adolescents (11–17 years), the in-hospital mortality was ten-times higher for COVID-19 than for influenza (five [1·1% of 458 vs one [0·1%] of 804), and patients with COVID-19 were more frequently obese or overweight.

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Interpretation

The presentation of patients with COVID-19 and seasonal influenza requiring hospitalisation differs considerably. Severe acute respiratory syndrome coronavirus 2 is likely to have a higher potential for respiratory pathogenicity, leading to more respiratory complications and to higher mortality. In children, although the rate of hospitalisation for COVID-19 appears to be lower than for influenza, in-hospital mortality is higher; however, low patient numbers limit this finding. These findings highlight the importance of appropriate preventive measures for COVID-19, as well as the need for a specific vaccine and treatment.

Funding

French National Research Agency.

Introduction

In December, 2019, a new disease now known as COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a major world threat. Considering its ability to spread and the relatively low case-fatality rates initially reported in China, SARS-CoV-2 was thought to be more similar to influenza than SARS-CoV-1.The preventive measures for this new infection were based on a comparison with the influenza virus because the viruses have similar modes of transmission and cause respiratory disease. Patients with COVID-19 were also anticipated to benefit from the clinical knowledge and care management of influenza.

A global pandemic was declared on March 11, 2020. By July 10, 2020, more than 12 million cases of COVID-19 and 554 000 COVID-19-related deaths had been identified worldwide. In France, it had already caused more than 30 000 deaths, nearly 20 000 of which were in hospital. At this point, COVID-19 had developed into a pandemic associated with substantial morbidity and mortality, putting great strain on hospitals and the health system in generall

Research in context
Evidence before this study

We searched PubMed with the terms “COVID-19” and “influenza” for articles in any language published up to July 16, 2020, that compared clinical characteristics, intensive care unit (ICU) admission, morbidity, and mortality of patients hospitalised for COVID-19 and for seasonal influenza. After excluding co-infection studies and studies of influenza pandemics, we identified five studies. An international study compared comorbidity and previous medications in adult patients (≥18 years) hospitalised either for COVID-19 or for seasonal influenza over the 2014–19 period. Another study focused on the risk of ischaemic stroke, including ICU admission and in-hospital mortality, of adult patients visiting emergency departments or hospitalised for COVID-19 in 2020 in two New York hospitals compared with adult patients with seasonal influenza from 2016 to 2018. The three other studies identified by our search had smaller populations. One small study was done in a French hospital and compared adult patients, and another focused on children younger than 1 year, comparing those hospitalised for influenza in the past few years to published features of COVID-19 in low-income and middle-income countries. Finally, another small study compared the clinical characteristics and treatments of children under the age of 5 years hospitalised in Wuhan for COVID-19 or influenza. Therefore, little information is available on the comparative burden of COVID-19 and seasonal influenza, particularly in children, who are considered to be at low risk of severe disease.

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Added value of this study

This study provides novel information about hospitalised patients with COVID-19. Our analysis uses a large national database including more than 89 000 patients with COVID-19 and more than 45 000 patients with seasonal influenza, including patients of all ages. We identified excess mortality associated with COVID-19 relative to seasonal influenza, with an age-standardised mortality ratio of 2·8. We evaluated differences between the characteristics of the two epidemics by age group, and more specifically in children aged 0–5 years (around 600 patients with COVID-19 and 7000 with influenza) and 6–17 years (around 600 patients with COVID-19 and 2000 with influenza).

Implications of all the available evidence

In-hospital case mortality was found to be higher in younger patients with COVID-19 compared with younger patients with influenza, even though children were at a lower risk of hospitalisation for COVID-19 than for influenza (as observed in our study and previously). However, the findings relating to deaths in children with COVID-19 are based on small numbers and should be treated with caution. More generally, the severe forms of COVID-19 and seasonal influenza requiring hospitalisation differ considerably. This underlines the need for additional studies to better characterise and understand the role and relative importance of risk factors associated with COVID-19 mortality, such as obesity, particularly in adolescents. This study also reinforces the importance of preventive and curative measures against both diseases. These data are particularly relevant as the epidemic continues to grow around the world and several countries prepare for potential overlapping of the seasonal influenza and COVID-19 epidemics.

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The case-fatality rate in COVID-19 appears to be higher than in seasonal influenza, even though both diseases mainly affect older adults (>65 years) with frailty. The higher case-fatality of COVID-19 could be due to differences in underlying comorbidities of patients, the pathogenicity of the virus, population immunity, and host responses to infection. For example, vaccines and approved treatments are available for influenza but not for COVID-19. Moreover, the considerable strain that was put on hospitals within a short period of time led to limitations in available care for the patients who were most frail.

Few studies have directly compared the respective burdens of the COVID-19 and influenza epidemics., , A comprehensive assessment of the outcomes and mortality of the two diseases and risk factors for hospitalisation and mortality could be used to identify specific at-risk populations, to strengthen and focus specific preventive measures in these populations, and to help define the future needs of health-care facilities. The aim of the present study was to compare, using French nationwide data, the population hospitalised for COVID-19 and the population hospitalised for influenza during the 2018–19 season, and to assess the differences in terms of risk factors, clinical characteristics, and outcomes.

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