Case Report: Co-infection with SARS-CoV-2 and influenza H1N1 in a patient with acute respiratory distress syndrome

Introduction

Coinfections involving SARS-CoV-2 and respiratory viruses influenza viruses (A or B) have been rarely reported^1–6. To date, there is no published case with a co-infection between SARS-CoV2 and influenza H1N1.

Case Report

A 41-year-old man presented to the hospital’s emergency unit with fever and cough that has been progressing for several days. The SARS-CoV-2 RT-PCR test was positive on March 22^nd 2020. On March 24^th 2020, the patient had developed a dyspnea aggravation and was taken care of by a medical unity at home. He has a medical history of pulmonary sarcoidosis with a restrictive ventilatory syndrome, which was being treated with Methotrexate (15mg per week) and folinic acid (0,4mg one tablet per day). He also had malaria in 2004 from a trip to Central Africa.

Physical examination on the 24^th March revealed a respiratory rate of 41 breaths/minute (normal range (NR) 12–20 breaths/minute) and oxygen saturation SpO2 of 75% (reference range (R-R) 95–100%) on ambient air. The SpO2 became at 96% when given mask flow oxygen at a rate of 12l/minute. The patient was transferred to the emergency room with 97% SpO2, body temperature 37.2°C, and respiratory rate of 30 breaths per minute. The patient presented with superficial polypnea, dyspnea with little effort, difficulty in speaking and bilateral “crackles”. Neurological and cardiovascular examinations were normal.

On supplemental oxygen (12l/min), arterial blood gas analysis revealed pH 7.50 (R-R 7.35–7.45), PCO₂ 35 mmHg (NR 35–45 mmHg), PO₂ 88 mmHg (NR 75–100 mmHg), HCO3- 27.3 mmol/l (R-R 22–26 mmol/l), and SaO2 94.4% (R-R 95–100%). The patient was then transferred to intensive care unit (ICU). Respiratory panel tests were negative for adenovirus (subtypes 2, 3, 6, 7.1 and 8), coronaviruses (229E, HKU1, NL63 and OC43), human metapneumovirus, rhinovirus, enterovirus, MERS-CoV, parainfluenza virus (1,2,3 and 4), respiratory syncytial virus, and Bordetella pertussis and parapertussis. However, influenza A, subtype influenza A-H1 variant 2009, was positive.

A chest computed tomography scan revealed a predominant left interstitial lung condensation syndrome. Routine laboratory tests revealed higher parameters during patient hospitalization: creatine phosphokinase 2999 UI/l (R-R 30–200UI/l); gamma glutamyl transferase 119 Ui/l (R-R 12–64UI/l); D-Dimers, which has increased two fold in one week, 3620 ng/ml (April 6^th) to 7520 (April 15^th ) (R-R 40–500UI/l). Other parameters were also elevated: fibrinogen 8.58g/l (R-R 2–4g/l); aspartate-aminotransferase 55 UI/l (R-R 5–34UI/l); platelets 599x10e9/l (April 7^th) (R-R 150–450x10e9/l); leukocytes 15.4x10e9/l (R-R 4–10x10e9/l) (Table 1).

Other parameters showed decreased values such as red cells, hemoglobins, hematocrits and mean corpuscular hemoglobin content (Table 1). The number of leukocytes and neutrophils underwent fluctuations with high rates between April 7^th and 10^th (Figure 1). In this period, bacteriological examination culture revealed infection by additional pathogens, with the presence of yeasts (Candidate albicans) and bacteria (Klebsiella pneumoniae) in bronchial sampling, probably with nosocomial origin.

Figure 1. Dynamic profile of laboratory findings in patient with coinfection including SARS-CoV-2 and influenza H1N1.

RdRp: RNA-dependent RNA polymerases; N: envelope protein N; S: Spike protein; CpK: creatine phosphokinase; SARS-CoV-2: severe acute respiratory syndrome coronavirus-2; Mar: March; Apr: April; #: Total count. The values between parentheses ‘()’ in the ordinate axis correspond to the reference range values.

The patient stayed at ICU for 26 days from March 24^th to April 19^th with orotracheal intubation and using Etomidate (40 mg intravenous dose) for sedation and 120mg of Celocurine for curarization. Enoxaparin (40mg /day) was administered by subcutaneous injection as a preventive anticoagulation up to April 1^st and increased to 80 mg/day according to the patient being overweight (Body Mass Index 33.8) and to evolution of biological criteria (D-Dimers 1890ng/l, Fibrinogen 10.82g/l, platelets 528x10e9/l). Unfractionated heparin was used as relay according to the high probability of pulmonary embolism. Mechanical ventilation was used with several sessions of prone position and then oxygen therapy on April 19^th. He was treated with hydroxychloroquine for 10 days (Plaquenil, 200mg every eight hours), and by Oseltamivir (4 days, oral suspension 6mg/ml: 75mg twice/day) for influenza H1N1 infection. Klebsiella pneumonia infection was treated using Meropenem (intravenous 1 g every four hours) from 6^th to 15^th April and Enterococcus faecalis infection was treated using Clamoxyl (intravenous 2 g every eight hours). Venous echodoppler performed on April 14^th found no thrombosis and no pulmonary embolism.

On April 19^th, the patient was transferred to the pulmonology department where he has a good respiratory evolution allowing oxygen weaning on April 23^rd. He was discharged on April 28^th, receiving kinesitherapy treatment, and taking a preventive anticoagulant therapy (Enoxaparine 4000 IU /0.4ml once daily by SC injection) for three weeks. The patient was integrated into the post COVID-19 rehabilitation program.

Discussion

We report, to the best of our knowledge, the first case of coinfection with SARS-CoV-2 and seasonal influenza H1N1. The low incidence rate of this co-infection reported in France may be explained by the late screening for COVID-19, which started in France in March 2020, which corresponds with the tapering off period for H1N1⁷. The prolonged intensive care and detection of SARS-CoV-2 viral RNA on the bronchoalveolar sample for at least three weeks might be explained by patient immunosuppression caused by lung polyinfection (viral, bacterial and fungal) and probably by his medical history of pulmonary sarcoidosis with a restrictive ventilatory syndrome.

Bacterial coinfections in COVID-19 patients have been reported in nine studies with a rate of 8% (62/806) of bacterial/fungal co-infection cases⁸. A few cases have been reported with co-infection with SARS-CoV-2 and influenza viruses (A or B)^1–6. Ding et al. has reported coinfected patients with SARS-CoV-2 and influenza virus and showed similar clinical characteristics as those patients with COVID-19 only, hence not all patients need ICU³. However, in a report by Cuadrado-Payán et al., all COVID-19 patients studied attended the emergency unit but had medical history of hypertension, end-stage kidney disease, or type 2 diabetes⁵.

The co-detection of SARS-CoV-2 and Influenza H1N1 in our case demonstrates the challenge to screen in the onset of the respiratory illness for a panel of viruses, which have overlapping clinical patterns and might exacerbate clinical symptoms, increase morbidity and prolong ICU stay. Hence, this case highlights the higher risk and poor outcomes caused by co-infection and the importance to achieve a differential diagnosis of respiratory distress syndromes, to limit contamination and adapt therapeutic strategies.

Consent

Written informed consent was obtained from the patient for the publication of this article and any associated images.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.