Complications of influenza in 272 adult and pediatric patients in a German university hospital during the seasonal epidemic 2017–2018

We performed a retrospective analysis of all patients with laboratory-confirmed infection with influenza A or B viruses between December 2017 and May 2018 in the Rostock University Medical Center, a 1100-bed tertiary referral hospital. All hospitalized patients as well as patients admitted to the emergency room or treated in outpatient clinics were included. The ethical committee of the Rostock University Medical Center approved the study (A 2018-0039). Informed consent was not required due to the observational nature of the study. Diagnostic procedures of respiratory specimens were performed using antigen immunoassays (QuickVue Influenza A + B Test, Quidel Corporation, San Diego, USA) and molecular analysis (GeneXpert® Flu/RSV XC-System, Cepheid, Sunnyvale, USA), according to the manufacturers’ protocols. If the antigen test was negative, a polymerase chain reaction (PCR) was performed. All patients with positive influenza antigen or positive influenza PCR were included. In case of repeated positive influenza tests, only the first test was included.

Two of the authors extracted clinical data from the electronic health records and the manual charts including demographics; comorbidities; prior influenza vaccination; presenting symptoms; duration from onset of symptoms to diagnosis; laboratory, microbiological, and radiographic findings; intensive care unit (ICU) admission; mechanical ventilation; hemodialysis; antimicrobial therapy; complications; and length of stay. The primary outcome was the occurrence of complications and in-hospital mortality.

Nosocomial influenza infection was defined as beginning of symptoms while a patient was in the hospital for ≥72 h prior to a positive test for influenza A or B. Pneumonia was defined as occurrence of new infiltrates on chest X‑ray or computed tomography (CT) scan described by a radiologist. Myocardial infarction was defined as signs of cardiac ischemia and increase of troponin T above the upper level of normal range. ST-elevation myocardial infarction (STEMI) was diagnosed if clinical signs of myocardial infarction were present and new ST elevation was detected.

During the winter season 2017–2018, a total of 934 influenza tests were performed in the Rostock University Medical Center, Germany, between October 2017 and May 2018. Of these, 293 were positive (31.4%), 82 for influenza A (28.0%) and 211 for influenza B (72.0%), corresponding to 272 cases, some of which were tested repeatedly. There were almost twice as many tests performed as in the previous season, 2016–2017, when 435 tests gave 91 positive results (20.9%), 87 for influenza A (95.6%) and four for influenza B (4.4%). While tests had been performed since October 2017, the first positive test was seen in January 2018: between January 5 and April 10, 2018, 272 patients were diagnosed with virologically confirmed influenza (Table 1). Twenty-three adult patients had a nosocomial influenza infection.

A total of 182 adult patients were included in the study, 145 were hospitalized. Complications occurred in 124 adult patients (68%): 73 developed pneumonia, bacterial pathogens were established in six cases (three S. pneumoniae, two S. aureus, one co-infection with E. coli and Pseudomonas aeruginosa). Seventeen patients were diagnosed with sepsis (14 of them associated with pneumonia), bacterial pathogens were identified in six cases (two S. aureus, two enterococci, one S. pneumoniae, one E. coli). Eleven patients developed myocardial infarction, two of them STEMI and nine patients non-STEMI. The infarction occurred within 0–7 days after the beginning of the influenza symptoms, three had influenza A, eight had influenza B, none of them died. One 74-year-old man with influenza B developed perimyocarditis complicated by nonfatal cardiogenic shock. Other complications were transient ischemic attacks in two patients and ischemic stroke in one patient who also had a myocardial infarction.

Adult patients with influenza A were significantly younger (62.62 ± 18.47 years) than patients with influenza B (70.27 ± 16.59 years, p = 0.013) and they were significantly more likely to be transmitted to the ICU (7/40 versus 7/141, p = 0.006) and mechanically ventilated (6/40 versus 6/141, p = 0.011). There was no significant difference between patients with influenza A versus influenza B in the overall complication rate (24/40 vs. 77/141, respectively, p = 0.544) or mortality rate (2/40 versus 9/141, respectively, p = 0.747).

Nine men and two women died 3–27 days after the onset of influenza symptoms, two of them with influenza A (5.0% of all influenza A patients), and nine with influenza B (6.4% of all influenza B patients). The cause of death was pneumonia in 10 patients and cardiac arrhythmia in one patient with acute exacerbation of chronic obstructive pulmonary disease (COPD) and gastrointestinal hemorrhage. All 11 patients who died had at least one underlying disease (see Table 2). Preexistent cardiac insufficiency was a significant risk factor for mortality, 7 of 51 patients with cardiac insufficiency (13.7%) died compared to 4 of 126 patients without cardiac insufficiency (3.2%, p = 0.008). Other significant risk factors for mortality were development of pneumonia, sepsis, acute renal failure, or intensive care treatment (see Table 2). Oseltamivir treatment was given to 94 of 182 (51.6%) adult patients.

Information on influenza vaccination status was available for 149 adults (Table 3), 55 received a trivalent and four a tetravalent vaccine. Pneumonia occurred significantly less frequently in vaccinated persons than in non-vaccinated persons (18/59 = 30.5% versus 47/90 = 52.2%, p = 0.036). The overall complication and mortality rate of unvaccinated patients was higher than in vaccinated adults; however, these differences failed to reach significance. The rate of vaccination was significantly higher in patients ≥60 years (54/115; 47.0%) than in patients <60 years (5/34; 14.7%; p = 0.001). However, only 57/139 (41.0%) of all patients with any indication for vaccination (age ≥60 years and/or medical indication for vaccination) had received a prior seasonal influenza vaccine.

Whereas 9/59 (15.2%) of the vaccinated patients were infected with influenza A virus, the others (50/59, 84.7%) had influenza B. Of those vaccinated with a tetravalent vaccine, one had influenza A und three influenza B viruses.

Ninety influenza cases were diagnosed in 89 children (see Table 1). One 7‑year-old boy developed influenza B, followed by influenza A 4 weeks later; he had no complications. Twenty-eight children (31.1%) were hospitalized (11 with influenza A, 17 with influenza B). Fifteen children (median age 5 years, range 0–16) developed one or more complications: five children had lower respiratory tract infections (one 11-month-old boy with respiratory failure due to influenza A and pneumonia with S. pneumonia, three children aged 3, 4, and 5 years with bronchitis due to influenza A, and one 10-year-old girl with influenza B pneumonia). Six children had a meningeal irritation (2, 2, 4, 14, 15, and 16 years), three had febrile seizures (2, 6, and 10 years), one an otitis media (9 years), and one a myositis (6 years). Complications were more frequently observed with influenza A (9/11; 81.8%, versus influenza B: 6/17; 35.3%, p < 0.05). Five patients had to be treated in the ICU: a 12-day-old boy with fever (influenza B), a 5-year-old immunosuppressed girl with high fever of 41 °C (influenza B), an 8-year-old boy with severe epistaxis (influenza B), a 10-year-old girl with febrile seizures and respiratory failure due to influenza B pneumonia treated with high-flow oxygen therapy, and one 16-year-old girl with meningeal irritation (influenza A). No child was mechanically ventilated. One child was treated with oseltamivir. No child died due to influenza. Children with influenza A were significantly younger than those with influenza B (6.13 ± 5.16 years versus 8.35 ± 4.24 years, p = 0.014).