Survival during influenza-associated bacterial superinfection improves following viral- and bacterial-specific monoclonal antibody treatment

Robinson, Keven M.; Ramanan, Kavita; Tobin, Joshua M.; Nickolich, Kara L; Pilewski, Matthew J; Kallewaard, Nicole L.; Sellman, Bret R.; Cohen, Taylor S.; Alcorn, John F.

doi:10.1172/jci.insight.125554

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…SARS-CoV-2 and influenza viruses share similar aspects, from their ease of transmission from person-to-person through the respiratory droplet route to their clinical presentation. In fact, both viruses can cause acute respiratory failure that might require hospitalization in ICU, might be complicated by bacterial and fungal superinfections and might predispose subjects to the development of thrombosis [4][5][6][7][8][9][10][11].…”

Section: A Oliva and G Ceccarelli Have Authors Contributed Equally To This Papermentioning

confidence: 99%

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission

et al. 2021

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Background Little is known in distinguishing clinical features and outcomes between coronavirus disease-19 (COVID-19) and influenza (FLU). Materials/methods Retrospective, single-centre study including patients with COVID-19 or FLU pneumonia admitted to the Intensive care Unit (ICU) of Policlinico Umberto I (Rome). Aims were: (1) to assess clinical features and differences of patients with COVID-19 and FLU, (2) to identify clinical and/or laboratory factors associated with FLU or COVID-19 and (3) to evaluate 30-day mortality, bacterial superinfections, thrombotic events and invasive pulmonary aspergillosis (IPA) in patients with FLU versus COVID-19. Results Overall, 74 patients were included (19, 25.7%, FLU and 55, 74.3%, COVID-19), median age 67 years (58–76). COVID-19 patients were more male (p = 0.013), with a lower percentage of COPD (Chronic Obstructive Pulmonary Disease) and chronic kidney disease (CKD) (p = 0.001 and p = 0.037, respectively) than FLU. SOFA score was higher (p = 0.020) and lymphocytes were significantly lower in FLU than in COVID-19 [395.5 vs 770.0 cells/mmc, p = 0.005]. At multivariable analysis, male sex (OR 6.1, p < 0.002), age > 65 years (OR 2.4, p = 0.024) and lymphocyte count > 725 cells/mmc at ICU admission (OR 5.1, p = 0.024) were significantly associated with COVID-19, whereas CKD and COPD were associated with FLU (OR 0.1 and OR 0.16, p = 0.020 and p < 0.001, respectively). No differences in mortality, bacterial superinfections and thrombotic events were observed, whereas IPA was mostly associated with FLU (31.5% vs 3.6%, p = 0.0029). Conclusions In critically ill patients, male sex, age > 65 years and lymphocytes > 725 cells/mmc are related to COVID-19. FLU is associated with a significantly higher risk of IPA than COVID-19.

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Section: A Oliva and G Ceccarelli Have Authors Contributed Equally To This Papermentioning

confidence: 99%

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission

et al. 2021

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“…The middle and caudal lobes of the right lung were homogenized under liquid nitrogen for RNA extraction using the Absolutely RNA Miniprep Kit (Agilent Technologies, Santa Clara, CA). RNA was reverse transcribed into cDNA using the iScript cDNA synthesis kit (Bio-Rad, Hercules, CA), which was assayed by real-time PCR for gene expression with Assay-on-Demand TaqMan primer and probe sets (Life Technologies, Grand Island, NY) (16). The left lung was fixed in 10% neutral buffered formalin for histopathology scoring of H&E-stained sections.…”

Section: Analysis Of Lung Inflammationmentioning

confidence: 99%

Influenza Suppresses Neutrophil Recruitment to the Lung and Exacerbates Secondary Invasive Pulmonary Aspergillosis

Tobin

Nickolich

Ramanan

et al. 2020

The Journal of Immunology

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Aspergillus fumigatus is an environmental fungus that can cause invasive pulmonary aspergillosis when spores are inhaled into the respiratory tract and invade airway or lung tissue. Influenza is a common respiratory virus that can cause severe respiratory disease, and postinfluenza invasive pulmonary aspergillosis, which is becoming a well-recognized clinical problem, typically occurs in critically ill patients. Mice challenged with influenza A PR/8/34 H1N1 and subsequently challenged with A. fumigatus had increased fungal burden, viral burden, inflammation, and mortality compared with single infected mice. Neutrophil recruitment in the lung of superinfected mice was decreased; however, mice were not neutropenic, and there was no difference in absolute blood neutrophils between groups. Additionally, CXCL1 and CXCL2 were decreased in lungs of superinfected mice compared with controls. IFN levels were increased in mice that received influenza, and deletion of STAT1 resulted in decreased fungal burden, increased airway and lung neutrophils, and increased CXCL1 compared with wild-type mice, whereas deletion of STAT2 did not change fungal burden or airway neutrophilia compared with wild-type mice. These data demonstrate a mechanism by which influenza A-induced STAT1 signaling inhibits neutrophil recruitment and increases susceptibility to postinfluenza invasive pulmonary aspergillosis.

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Influenza sequelae: from immune modulation to persistent alveolitis

2020

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Abstract Acute influenza virus infections are a global public health concern accounting for millions of illnesses worldwide ranging from mild to severe with, at time, severe complications. Once an individual is infected, the immune system is triggered in response to the pathogen. This immune response can be beneficial ultimately leading to the clearance of the viral infection and establishment of immune memory mechanisms. However, it can be detrimental by increasing susceptibility to secondary bacterial infections and resulting in permanent changes to the lung architecture, in the form of fibrotic sequelae. Here, we review influenza associated bacterial super-infection, the formation of T-cell memory, and persistent lung injury resulting from influenza infection.

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Survival during influenza-associated bacterial superinfection improves following viral- and bacterial-specific monoclonal antibody treatment

Cited by 3 publications

References 41 publications

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission

Influenza Suppresses Neutrophil Recruitment to the Lung and Exacerbates Secondary Invasive Pulmonary Aspergillosis

Influenza sequelae: from immune modulation to persistent alveolitis

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