key: cord-0685856-9t0edf73 authors: Cheng, Yuan; Ma, Jing; Wang, He; Wang, Xi; Hu, Zhanwei; Li, Haichao; Zhang, Hong; Liu, Xinmin title: Co‐infection of influenza A virus and SARS‐CoV‐2: A retrospective cohort study date: 2021-01-27 journal: J Med Virol DOI: 10.1002/jmv.26817 sha: e1cb6277bc1cd94dfc86b1f7a4ba1e30e2c0dbaf doc_id: 685856 cord_uid: 9t0edf73 The coronavirus 2019 (COVID‐19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread across the world and is responsible for over 1,686,267 deaths worldwide. Co‐infection with influenza A virus (IFV‐A) during the upcoming flu season may complicate diagnosis and treatment of COVID‐19. Little is known about epidemiology and outcomes of co‐infection. Data for 213 COVID‐19 patients treated at Tongji Hospital in Wuhan from January 28, 2020 to March 24, 2020 were retrospectively analyzed. Ninety‐seven of the patients (45.5%) tested positive for anti‐ IFV‐A immunoglobulin M antibodies. The clinical characteristics were described and analyzed for patients with SARS‐CoV‐2 infection only and patients with SARS‐CoV‐2/IFV‐A co‐infection. Patients with co‐infection showed similar patterns of symptoms and clinical outcomes to patients with SARS‐CoV‐2 infection only. However, an increased expression of serum cytokines (interleukin‐2R [IL‐2R], IL‐6, IL‐8, and tumor necrosis factor‐α) and cardiac troponin I, and higher incidence of lymphadenopathy were observed in patients with SARS‐CoV‐2 infection only. Male patients and patients aged less than 60 years in the SARS‐CoV‐2 infection group also had significantly higher computed tomography scores than patients in co‐infection group, indicating that co‐infection with IFV‐A had no effect on the disease outcome but alleviated inflammation in certain populations of COVID‐19 patients. The study will provide a reference for diagnosing and treating IFV‐A and SARS‐CoV‐2 co‐infection cases in the upcoming flu season. for Disease Control, an estimated 30 million to 56 million people were infected with IFV-A resulting in 24,000-62,000 deaths in the 2019-2020 flu season. 3 In Wuhan, China, a retrospective analysis revealed a significant rise in reported influenza-like illness during October 2019 to January 2020, in comparison to previous years. 4 Up to July 19, 2020, the Southern hemisphere reported an interseasonal level of influenza activity. 5 There are a few cases of co-infection of SARS-CoV-2 and IFV-A worldwide. [6] [7] [8] [9] [10] However, information on the correlation between SARS-CoV-2 and IFV-A infection is still limited. In the present study, the clinical characteristics, diseases outcomes and laboratory testing data of patients with SARS-CoV-2 infection only (SARS-CoV-2(+) IFV-A(−)) and patients with SARS-CoV-2 who are coinfected with IFV-A (SARS-CoV-2(+) IFV-A(+)) were described and compared. years. Patients without local computed tomography (CT) scan results or serum immunoglobulin M (IgM) antibody test to IFV-A, those whose symptoms from date of CT scan was greater than 60 days, and those with a history of pneumonectomy were excluded from the study. The study was approved by the Research Ethics Commission of Peking University First Hospital (2020098). The access to patient records was authorized, and all patients' information were kept confidential. Included patients were divided into two groups: SARS-CoV-2(+) IFV-A(−) and SARS-CoV-2(+) IFV-A(+) based on serumspecific IgM antibody test for IFV-A at admission. The first chest CT scan after admission was collected for analysis. Epidemiological, demographic, clinical, laboratory and outcome data were collected using standardized data collection forms. All data were independently reviewed by two physicians (CY and WX) and any discrepancies between the two primary reviewers were resolved with adjudication by a third researcher (HZW). COVID-19 was diagnosed by RT-PCR test (C t cut-off value of 38) of throat swabs and by chest CT. The ORF1ab and nucleocapsid (N) gene was utilized as gene target for RT-PCR assay according to recommendations of Chinese Center for Disease Control. Diagnosis of influenza virus infection was based on serological detection of IFV-Aspecific IgM antibody (titer >1:10) (indirect immunofluorescence assay, EUROIMMUN FI2821-17M). Bio-Plex Pro Human Cytokine Panel were used to measure plasma cytokine levels. The first chest CT scans after admission were collected for analysis. The chest CT scan images were independently reviewed by one experienced pulmonologist and one experienced radiologist (CY, WH). Consensus was reached after discussion when there was a controversy. CT findings included ground glass opacity (GGO), consolidation, and fibrosis. GGO was defined as hazy increased attenuation of the lung, but with preservation of bronchial and vascular margins. Consolidation was defined as homogeneous increase in pulmonary parenchyma that obscures the margins of vessels and airway walls, and fibrosis was defined as distorted consolidation, traction bronchiectasis, and interlobular septal thickening. Lymphadenopathy was defined as a lymph node larger than 1 cm in diameter. The CT scans were scored on the axial images as previously reported. 11, 12 Briefly, the extent of abnormality and distribution of affected lung parenchyma were independently recorded for the upper, middle, and lower zones of each side. The CT findings were graded using a threepoint scale: score of 1, normal attenuation, score of 2, ground-glass attenuation, and score of 3, consolidation. According to the distribution of the affected lung parenchyma, each lung zone was scored as follows: 0 as normal, 1 as less than 25% abnormality, 2 as 25%-50% abnormality, 3 as 50%-75% abnormality, and 4 as greater than 25% abnormality. The fourpoint scale of the lung parenchyma distribution was then multiplied by the three-point scale of abnormality. The scores from all six zones were added for a final cumulative score that ranged from 0 to 72. As shown in Figure 1 , during the study period (from January 28 to Linear atelectasis was typically manifested as linear soft tissue opacities ranging from 1 to 3 mm in thickness and 1 to 5 cm in length, located in subpleural regions. There was no significant difference in fibrosis and linear atelectasis between the two groups. Co-infection is generally considered to worsen disease outcomes and may lead to more severe symptoms. Co-infections may however modify the virulence of the virus and cell death, therefore altering in Jiansu province, although the overall co-infection rate of respiratory pathogens was up to 94.2%. 23 The difference might be attributable to seasonality, vaccination coverage, enrolled numbers as well as regions. Additionally, consistent with a previous report, 16 our data showed that COVID-19 patients coinfected with IFV-A presented with symptoms and clinical outcomes similar to those with single SARS-CoV-2 infection. In other studies by Ma et al. 21 and Yue et al., 24 SARS-COV-2 co-infection with influenza, especially influenza B virus, could lead to poor outcomes. As is well known, the acute increase in secretion of cytokines, such as IL-2, IL-6, IL-8, and TNF-α, also called cytokine storm, is associated with COVID-19 disease severity. 25, 26 Additionally, increased D-dimer (a thrombosis marker) and cTnI concentration were associated with increased incidence of mortality in patients with COVID-19. [27] [28] [29] Patients with co-infection showed significant reduction in cytokines and cTnI, indicating that patients thus, systematic testing for SARS-CoV-2 and influenza are necessary, and influenza vaccination is recommended not only to reduce the risk of co-infection, but also for the potential benefit to the immune system. 31 Further studies with larger sample sizes from multiple sites are also warranted to study the prognosis and treatment of coinfected patients. Funds for the Central Universities (No. BMU2020HKYZX003). The authors declare that there are no conflict of interests. 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