Medical features of COVID-19 and influenza infection: A comparative study in Paris, France

Abstract

•COVID-19 and influenza patients share overweight as a risk factor for severe infection.•Higher death rate was reported in COVID-19 group than in influenza group.•COVID-19 patients developed preferentially secondary respiratory failure.•Older age and diabetes were confirmed as major contributing death risk factors in COVID-19. In this Journal, Zheng et al. have report the symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection -named coronavirus disease 2019 (COVID-19)- appear very similar to influenza.1Zheng X. Wang H. Su Z. et al.Co-infection of SARS-CoV-2 and influenza virus in early stage of the COVID-19 epidemic in Wuhan.China J Infect. 2020; 81: e128-e129https://doi.org/10.1016/j.jinf.2020.05.041Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar We would like to share our findings for SARS-CoV-2 and influenza virus infections as virus co-circulation is likely to occur in future.2Kissler Stephen M. Christine Tedijanto Edward Goldstein Grad Yonatan H. Marc Lipsitch Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period.Science. 2020; 368: 860-868https://doi.org/10.1126/science.abb5793Crossref PubMed Scopus (1466) Google Scholar It is important to facilitate differential diagnosis. We therefore conducted a retrospective study to further explore specific features and to better characterize risk factors for severe illness. This retrospective study included 200 inpatients from the Pitié-Salpêtrière University Hospital (Paris, France) with SARS-CoV-2 (n = 100, ‘COVID-19 group’) or influenza (n = 100, ‘influenza group’) laboratory-confirmed infections on respiratory specimens between January 1st-March 25th, 2020. Patients with complete baseline clinical and biological available data were consecutively included. The study was approved by the Comité Ethique de la Recherche of Sorbonne University (approval number CER 2020–44). Demographic, biological, treatment, and clinical outcome data were extracted from medical records using a standardized form. We collected date of symptom onset, comorbidities, radiographic findings upon admission, and relevant data concerning hospital courses (overall duration of stay, and transfer in intensive care unit [ICU] and supportive care ward). Clinical outcomes were monitored up to April 11th, final date of follow-up. Overweight/obesity was defined as body mass index (BMI) >25 kg/m2. Variables are presented as ‘median’ (interquartile ranges; IQR) or ‘number of’ (%). We used the Mann-Whitney U test, χ2 test, or Fisher's exact test to compare groups, where appropriate. A two-sided α<0.05 was considered as statistically significant. Risk factors were analyzed by logistic regression analysis. We excluded variables from univariable analysis if their between-group differences were not statistically significant. Variables for multivariable analysis were chosen if p<0.20 in univariable analysis and if the number of events was sufficient to calculate odds ratios (OR). Analyses were performed using GraphPad Prism v.8. Baseline characteristics of the 200 patients included are shown in the Table 1. Overall, the median age was 60 (IQR=50–73; 42 females) and 61 (48–76; 44 females) in COVID-19 and influenza groups, respectively. Comorbidities were present in the majority of patients (>89%) with diabetes, hypertension, and overweight/obesity as most common comorbidities. However, influenza patients were more likely to have chronic pulmonary diseases (p = 0.01). Overweight/obesity rate (p = 0.02) and median BMI (p = 0.04) were significantly higher in COVID-19. At the time of diagnosis, the most frequent symptoms were fever (p = 0.63) and cough (p = 1.00) in both groups. COVID-19 patients complained more significantly about fatigue, faintness, diarrhea, and anosmia/ageusia. Conversely, sputum production (p = 0.0001) and nasal congestion (p = 0.02) were reported most frequently in influenza. The frequency of patients presenting with respiratory failure were similar in both groups (around 10.0%). However, secondary respiratory failure were only observed in COVID-19 (21%; p<0.0001). COVID-19 patients experienced more often acute kidney failure (p = 0.048) and pulmonary embolism (p = 0.03). Heart congestion was more frequent in influenza (p = 0.003). Notably, ground-glass opacities showed a trend towards higher frequency in COVID-19 patients, although not statistically significant (p = 0.06). Conversely, pulmonary nodules were much more observed in influenza (p = 0.001). Influenza patients had statistically higher levels of white blood cells, neutrophils, platelets, sodium, troponin, albumin than COVID-19 patients (Table 1). Both groups exhibited lymphocytopenia (around 80% of patients) (data not shown), however no significant median value difference was observed.Table 1Overall baseline characteristics of patients with COVID-19 or influenza.COVID-19# (n = 100)Influenza#Denominators of patients included in this analysis are shown if they differed from the overall numbers in the respective group. (n = 100)p valueDemographic characteristics Age, median (IQR) – years60 (50–73)61 (48–76)0.88 Sex – no. (%) Female42 (42.0)44 (44.0)0.89 Male58 (58.0)56 (56.0)0.89Occupation – no. (%) Active44/96 (45.8)32/85 (37.6)0.29 Health worker4/96 (4.2)4/85 (4.7)1.00 Unemployed16/96 (16.7)13/85 (15.3)0.84 Retired35/96 (36.5)38/85 (44.7)0.29Comorbidity – no./total no. (%) None10 (10.0)11 (11.0)1.00 Chronic lung disease12 (12.0)27 (27.0)0.01 Cardiovascular disease28 (28.0)30 (30.0)0.88 Chronic renal disease11 (11.0)7 (7.0)0.46 Solid cancer7 (7.0)14 (14.0)0.17 Organ transplant5 (5.0)5 (5.0)1.00 HIV infection1 (1.0)1 (1.0)1.00 HBV infection1 (1.0)1 (1.0)1.00 Pregnancy1 (1.0)1 (1.0)1.00 Hemopathy10 (10.0)13 (13.0)0.66 Neurodegenerative disease3 (3.0)5 (5.0)0.72 Splenectomy2 (2.0)2 (2.0)1.00 Autoimmune and system disease7 (7.0)8 (8.0)1.00CV risk factors – no./total no. (%) Presence of CV risk factors75/98 (76.5)66 (66.0)0.12 Diabetes24/98 (24.5)16 (16.0)0.16 Dyslipidemia15/98 (15.3)8 (8.0)0.12 Hypertension37/98 (37.8)38 (38.0)1.00 Overweight/obesity40/98 (40.8)25 (25.0)0.02 Obstructive sleep apnea8/98 (8.2)13 (13.0)0.36 Current smoker10/98 (10.2)11 (11.0)1.00 Former smoker15/98 (15.3)18 (18.0)0.70 Chronic alcoholism4/98 (4.1)5 (5.0)1.00BMI‡Data regarding BMI medians were available for 56 and 48 patients in COVID-19 and influenza groups, respectively. Median (IQR)27.3 (23.8–32.4)24.8 (21.7–28.6)0.04Symptoms – no./total no. (%) Fever92 (92.0)89 (89.0)0.63 Fatigue63/99 (63.6)39 (39.0)0.0006 Myalgia36/99 (36.4)24 (24.0)0.06 Dyspnea45 (45.0)51 (51.0)0.48 Cough81 (81.0)80 (80.0)1.00 Productive sputum12 (12.0)36 (36.0)0.0001 Nasal congestion8/96 (8.3)21 (21.0)0.02 Acute respiratory failure31 (31.0)9 (9.0)0.0002 On admission10 (10.0)9 (9.0)1.00 Secondary failure21 (21.0)0<0.0001 Headache25/99 (25.3)20 (20.0)0.40 Nausea19/97 (19.6)10 (10.0)0.07 Vomiting21/97 (21.6)11 (11.0)0.053 Diarrhea25/97 (25.8)13 (13.0)0.03 Anosmia/ageusia7 (7.0)00.01 Faintness12/99 (12.1)3 (3.0)0.02 Chest pain21 (21.0)16 (16.0)0.47Chest x-rays and CT-findings – no./total no. (%) Abnormalities on chest radiograph26/36 (72.2)24/49 (49.0)0.04 Bronchial syndrome1/36 (2.8)6/49 (12.2)0.23 Interstitial syndrome11/36 (30.6)2/49 (4.1)0.001 Alveolar syndrome5/36 (13.9)5/49 (10.2)0.74 Lobar consolidation5/36 (13.9)11/49 (22.4)0.41 Abnormalities on CT chest34/34 (100.0)21/22 (95.0)0.39 Ground-glass opacities29/34 (85.3)13/22 (59.1)0.06 Pulmonary nodules3/34 (8.8)11/22 (50.0)0.001 Lobar consolidation16/34 (47.1)11/22 (50.0)1.00Laboratory findings ¤For each biological variable, the number of digits after decimal point depends on technical precision. (unity; normal range) – Median (IQR)§Biological data from patients with COVID-19 and Influenza infection were available for hematological values in 100 patients, fibrinogen in 44 and 46 patients, sodium and potassium in 96 and 98 patients, chloride in 96 and 95 patients, bicarbonates in 79 and 85 patients, troponin in 32 and 35 patients, albumin in 7 and 24 patients, C-reactive protein in 64 and 73 patients, serum creatinine in 98 and 98 patients, total bilirubin in 44 and 65 patients, aspartate aminotransferase in 51 and 70 patients, alanine aminotransferase in 51 and 71 patients, ʏ-glutamyltransferase in 48 and 69 patients, creatine kinase in 23 and 34 patients, lactate dehydrogenase in 21 and 34 patients, arterial lactates in 51 and 36 patients, procalcitonin in 60 and 74 patients, arterial blood pH in 48 and 35 patients, respectively. BMI: body mass index; COVID-19: coronavirus disease 2019; CT: computed tomography; CV: cardiovascular; HBV: hepatitis B virus; HIV: human immunodeficiency virus; ICU: intensive care unit; IQR: interquartile range; no.: number of. p<0.05 was considered to be statistically significant. White-cell count (G/L; 4.00 – 10.00)5.88 (4.41–7.68)6.72 (5.15–9.42)0.01 Neutrophils (G/L; 2.00– 7.50)4.11 (2.99–5.65)5.06 (3.43–7.25)0.02 Lymphocytes (G/L; 1.50–4.00)1.08 (0.68–1.41)0.89 (0.66–1.35)0.41 Hemoglobin (g/dL; 13.0–17.5)13.6 (12.2–14.5)13.2 (11.6–14.3)0.29 Platelets (G/L; 150–400)179 (145–225)199 (168–239)0.04 Fibrinogen (g/L; 2–4)5.5 (4.2–6.7)5.4 (4.5–6.4)0.92 Activated partial thromboplastin time (s; <1.20)1.16 (1.10–1.30)1.14 (1.04–1.29)0.44 Prothrombin time (%; 70–120)98 (86–100)91 (76–100)0.08 Sodium (U/L; 136–155)137 (135–139)138 (136–140)0.006 Potassium (U/L; 3.4–5.1)4.1 (3.8–4.6)4.0 (3.7–4.4)0.09 Chloride (U/L; 98–107)99 (97–102)100 (97–103)0.35 Bicarbonates (mmol/L; 22 – 26)24 (22–26)25 (23–27)0.07 Troponin (ng/L; <0.60)9.2 (6.5–22.4)34.4 (8.8–72.2)0.007 Albumin (g/L; 35–52)30 (27–33)37 (33–39)0.04 C-reactive protein (mg/L; <5.0)47.37 (15.42–87.46)41.44 (15.25–82.05)0.55 Serum creatinine (µmol/L; 62–106)86 (70–117)87 (70–108)0.75 Total bilirubin (µmol/L; 2–17)8 (5–12)8 (5–12)0.99 Aspartate aminotransferase (U/L; 20–32)45 (34–76)34 (29–49)0.02 Alanine aminotransferase (U/L; 16– 35)31 (22–59)26 (20–42)0.21 γ -glutamyltransferase (U/L; 12–55)44 (26–101)32 (21–54)0.08 Creatine kinase (U/L; <190)178 (109–473)117 (65–378)0.42 Lactate dehydrogenase (U/L; 135–215)397 (305–544)298 (248–383)0.04 Arterial lactates (mmol/L; 0.5–1.8)1.0 (0.7–1.4)1.2 (0.9–1.4)0.09 Procalcitonin (µg/L; <0.10)0.12 (0.08–0.27)0.13 (0.07–0.36)0.74 Arterial blood pH (7.35–7.45)7.45 (7.42–7.48)7.43 (7.40–7.78)0.33Treatments – no./total no. (%) Oseltamivir11/95 (11.6)45/97 (46.4)<0.0001 Any antibiotics77/98 (78.6)58/97 (59.8)0.005 Amoxicillin/Clavulanic acid40/98 (40.8)33/97 (34.0)0.37 Cephalosporin48/98 (49.0)21/97 (21.6)<0.0001 Oxygen therapy65 (65.0)42/99 (42.4)0.002Complications – no./total no. (%) Pulmonary embolism6 (6.0)00.03 Acute kidney failure17 (17.0)7 (7.0)0.048 Myocarditis02 (2.0)0.50 Heart congestion2 (2.0)14 (14.0)0.003 Heart rhythm disorder7 (7.0)2 (2.0)0.17Clinical outcomes at data cutoff no./total no. (%) Admitted in ICU31 (31.0)12 (12.0)0.002 Discharged75 (80.0)94 (94.0)0.0003 Death20 (20.0)5 (5.0)0.002 Remained in hospital5 (5.0)1 (1.0)0.21# Denominators of patients included in this analysis are shown if they differed from the overall numbers in the respective group.‡ Data regarding BMI medians were available for 56 and 48 patients in COVID-19 and influenza groups, respectively.¤ For each biological variable, the number of digits after decimal point depends on technical precision.§ Biological data from patients with COVID-19 and Influenza infection were available for hematological values in 100 patients, fibrinogen in 44 and 46 patients, sodium and potassium in 96 and 98 patients, chloride in 96 and 95 patients, bicarbonates in 79 and 85 patients, troponin in 32 and 35 patients, albumin in 7 and 24 patients, C-reactive protein in 64 and 73 patients, serum creatinine in 98 and 98 patients, total bilirubin in 44 and 65 patients, aspartate aminotransferase in 51 and 70 patients, alanine aminotransferase in 51 and 71 patients, ʏ-glutamyltransferase in 48 and 69 patients, creatine kinase in 23 and 34 patients, lactate dehydrogenase in 21 and 34 patients, arterial lactates in 51 and 36 patients, procalcitonin in 60 and 74 patients, arterial blood pH in 48 and 35 patients, respectively.BMI: body mass index; COVID-19: coronavirus disease 2019; CT: computed tomography; CV: cardiovascular; HBV: hepatitis B virus; HIV: human immunodeficiency virus; ICU: intensive care unit; IQR: interquartile range; no.: number of. p<0.05 was considered to be statistically significant. Open table in a new tab The median time from illness onset to admission was 4 [1–6] and 2 [0–4] days for COVID-19 and influenza, respectively (p = 0.02, Fig. 1). COVID-19 patients more frequently required hospitalization (p = 0.001) (data not shown). Noteworthy, the median duration of overall hospital stay was significantly longer for COVID-19 than for influenza (10 [4–17] and 4 [1–11] days, respectively, p<0.0001). Overall, COVID-19 patients more frequently required oxygen therapy (p = 0.002) (Table 1). The median duration between onset of symptoms and aggravation was 7 (5–10) and 4 (2.5–6) days in COVID-19 and influenza groups, respectively (p<0.0001) (data not shown). Clinical worsening was linked to a higher ICU rate admission among COVID patients (p = 0.002). Baseline characteristics, clinical courses, outcome, and duration from illness onset concerning severe infections (31 and 12 severe COVID-19 and influenza, respectively) are shown in Supplementary Tables 1–3/Fig. 1. Noteworthy, no significant difference was evidenced concerning corticosteroid use comparing both severe infection groups (p = 0.84). In multivariable analysis, odds of severe COVID-19 were significantly higher in individuals with chronic lung disease (OR=6.45; p = 0.009), hypertension (3.05; p = 0.02), and overweight/obesity (3.23; p = 0.02). Obstructive sleep apnea and overweight/obesity were significantly associated with severe influenza in univariable analysis (p = 0.04 and p = 0.04, respectively) (Supplementary Tables 4–5). The mortality rate was significantly higher in COVID-19 group than in influenza group (20% vs. 5%; p = 0.002). Age and diabetes appear as death risk factors in COVID-19 in multivariable analysis (OR=1.06 [95% CI=1.02–1.11]; p = 0.004 and OR=4.50 [1.48–14.24]; p = 0.009, respectively) (Supplementary Table 6). To the best of our knowledge, this study is the largest case series to date comparing COVID-19 and influenza. COVID-19 patients more frequently reported dry cough, asthenia, diarrhea, anosmia/ageusia, and clinical worsening around 7 days after symptom onset, as previously described3Safiya Richardson Hirsch Jamie S. Mangala Narasimhan Crawford James M. McGinn Thomas Davidson Karina W. et al.Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.JAMA. 2020; https://doi.org/10.1001/jama.2020.6775Crossref Scopus (5344) Google Scholar, 4Lu Lin Xiayang Jiang Zhenling Zhang Siwen Huang Zhenyi Zhang Zhaoxiong Fang et al.Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection.Gut. 2020; 69: 997-1001https://doi.org/10.1136/gutjnl-2020-321013Crossref PubMed Scopus (528) Google Scholar, 5Changxing Shen Min Tan Xiaolian Song Guoliang Zhang Jiren Liang Hong Yu et al.Comparative analysis of early-stage clinical features between COVID-19 and influenza A H1N1 virus pneumonia.Front Public Health. 2020; 8: 206https://doi.org/10.3389/fpubh.2020.00206Crossref PubMed Scopus (19) Google Scholar, 6Souheil Zayet Juliette Kadiane-Oussou N'dri Quentin Lepiller Hajer Zahra Pierre-Yves Royer Lynda Toko et al.Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster.Microbes Infect. 2020; https://doi.org/10.1016/j.micinf.2020.05.016Crossref Scopus (112) Google Scholar. As previously reported, radiologic findings showed that ground-glass opacity was more common in COVID-19,3Safiya Richardson Hirsch Jamie S. Mangala Narasimhan Crawford James M. McGinn Thomas Davidson Karina W. et al.Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.JAMA. 2020; https://doi.org/10.1001/jama.2020.6775Crossref Scopus (5344) Google Scholar however it could be also observed during influenza.5Changxing Shen Min Tan Xiaolian Song Guoliang Zhang Jiren Liang Hong Yu et al.Comparative analysis of early-stage clinical features between COVID-19 and influenza A H1N1 virus pneumonia.Front Public Health. 2020; 8: 206https://doi.org/10.3389/fpubh.2020.00206Crossref PubMed Scopus (19) Google Scholar,6Souheil Zayet Juliette Kadiane-Oussou N'dri Quentin Lepiller Hajer Zahra Pierre-Yves Royer Lynda Toko et al.Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster.Microbes Infect. 2020; https://doi.org/10.1016/j.micinf.2020.05.016Crossref Scopus (112) Google Scholar We reported more severe cases requiring oxygenation therapy, a higher death rate, and a longer hospital stay in COVID-19 group. Moreover, COVID-19 patients also experienced disease aggravation around 7 days post-symptom onset, as previously reported.3Safiya Richardson Hirsch Jamie S. Mangala Narasimhan Crawford James M. McGinn Thomas Davidson Karina W. et al.Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.JAMA. 2020; https://doi.org/10.1001/jama.2020.6775Crossref Scopus (5344) Google Scholar,6Souheil Zayet Juliette Kadiane-Oussou N'dri Quentin Lepiller Hajer Zahra Pierre-Yves Royer Lynda Toko et al.Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster.Microbes Infect. 2020; https://doi.org/10.1016/j.micinf.2020.05.016Crossref Scopus (112) Google Scholar Both infection may evolve to respiratory failure,3Safiya Richardson Hirsch Jamie S. Mangala Narasimhan Crawford James M. McGinn Thomas Davidson Karina W. et al.Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.JAMA. 2020; https://doi.org/10.1001/jama.2020.6775Crossref Scopus (5344) Google Scholar,5Changxing Shen Min Tan Xiaolian Song Guoliang Zhang Jiren Liang Hong Yu et al.Comparative analysis of early-stage clinical features between COVID-19 and influenza A H1N1 virus pneumonia.Front Public Health. 2020; 8: 206https://doi.org/10.3389/fpubh.2020.00206Crossref PubMed Scopus (19) Google Scholar,6Souheil Zayet Juliette Kadiane-Oussou N'dri Quentin Lepiller Hajer Zahra Pierre-Yves Royer Lynda Toko et al.Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster.Microbes Infect. 2020; https://doi.org/10.1016/j.micinf.2020.05.016Crossref Scopus (112) Google Scholar however, COVID-19 patients developed preferentially secondary respiratory failure. Interestingly, inflammation marker levels were significantly higher in severe COVID-19 cases. It is well established that SARS-CoV-2 triggers an excessive harmful proinflammatory response7Qing Ye Bili Wang Jianhua Mao The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19.J Infect. 2020; 80: 607-613https://doi.org/10.1016/j.jinf.2020.03.037Abstract Full Text Full Text PDF PubMed Scopus (1654) Google Scholar promoting thrombotic events as pulmonary embolism.8Julien Poissy Julien Goutay Morgan Caplan Erika Parmentier Thibault Duburcq Fanny Lassalle et al.Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence.Circulation. 2020; https://doi.org/10.1161/CIRCULATIONAHA.120.047430Crossref Scopus (711) Google Scholar In our study, pulmonary embolism was only reported during COVID-19 (p = 0.03). COVID-19 and influenza patients commonly share overweight/obesity as risk factor for severe infection.9Luzi L. Radaelli M.G. Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic.Acta Diabetol. 2020; 57: 759-764https://doi.org/10.1007/s00592-020-01522-8Crossref PubMed Scopus (217) Google Scholar As previously reported, pre-existing hypertension and diabetes were additionally associated with a higher risk to develop severe COVID-19. Similarly, our study also confirmed older age and diabetes as major contributing death risk factors in COVID-19.3Safiya Richardson Hirsch Jamie S. Mangala Narasimhan Crawford James M. McGinn Thomas Davidson Karina W. et al.Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.JAMA. 2020; https://doi.org/10.1001/jama.2020.6775Crossref Scopus (5344) Google Scholar,10Hu Y. Sun J. Dai Z. et al.Prevalence and severity of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis.J Clin Virol. 2020; 127104371https://doi.org/10.1016/j.jcv.2020.104371Crossref PubMed Scopus (340) Google Scholar To conclude, we described similarities but also differences between COVID-19 and influenza, thereby providing some guidance for healthcare management. HF and MP had the idea for and designed the study. HF, MP, CC, and SB and had full access to the collected data and take responsibility for the integrity of the data and the accuracy of the data analysis. PH, CEL, MD, and VP assessed the accuracy of clinical data. HF, CC, and AJ processed statistical data. HF, CC, MP, DB, and SB drafted the paper. All authors critically revised the manuscript for intellectual content and gave final approval for the submitted version. We declare no competing interests. We acknowledge all healthcare workers involved in the diagnosis and treatment of patients.