Background The clinical presentation of severe acute respiratory syndrome coronavirus-2 infection is highly variable from asymptomatic infection to fulminant disease. The reasons for the variation are only starting to unravel, with risk factors including age and certain comorbidities as well as genetic defects causing immunological perturbations in the interferon pathways. Case presentation We report the case of an otherwise healthy Caucasian man, who at ages 60 and 64 years suffered from severe H1N1 influenza virus infection and severe acute respiratory syndrome coronavirus-2 infections, respectively. In both cases, there were acute kidney impairment and the need for intensive care unit admission as well as mechanical ventilation. Fortunately, after both infections there was full clinical recovery. The severity of the infections indicates an underlying impairment in the ability to control these kinds of infections. Challenge of patient peripheral blood mononuclear cells showed impaired type I and III antiviral interferon responses and reduced interferon-stimulated gene expression. However, despite investigation of patient samples by whole exome sequencing and enzyme-linked immunosorbent assay, no known disease-causing genetic variants related to interferon pathways were found, nor were interferon autoantibodies demonstrated. Thus, any underlying immunological cause of this unusual susceptibility to severe viral infections remains unresolved. Conclusion The patient experienced very similar severe clinical pictures triggered by H1N1 and severe acute respiratory syndrome coronavirus-2 infections, indicating an underlying inability to contain these infections. We were unable to show that the patient had any of the currently known types of immune incompetence but identified genetic changes possibly contributing to the severe course of both infections. Further analyses to delineate contribution factors are needed.
【저자키워드】 COVID-19, SARS-CoV-2, ICU, H1N1, Interferon (INF), 【초록키워드】 viral infection, Risk factors, intensive care, Antiviral, mechanical ventilation, Influenza, susceptibility, severity, Variation, Sequencing, Infection, interferon, Comorbidity, risk factor, severe acute respiratory syndrome Coronavirus, viral infections, immune, Peripheral blood, clinical recovery, Severe acute respiratory syndrome, enzyme-linked immunosorbent assay, infections, Viral, clinical picture, challenge, Patient, asymptomatic infection, age, H1N1, genetic variants, Genetic variant, virus infection, respiratory, H1N1 influenza, disease, expression, interferon response, Admission, Coronavirus-2, intensive care unit admission, Analysis, Genetic changes, Pathways, interferon pathway, Perturbation, autoantibody, mononuclear cells, mononuclear cell, acute respiratory syndrome, Factor, Exome, enzyme, genetic defects, type I, impairment, genetic change, genetic defect, interferon-stimulated gene, immunological, enzyme-linked immunosorbent, Course, healthy, the patient, reduced, indicate, demonstrated, suffered, contributing to, triggered, the interferon, acute kidney, disease-causing, 【제목키워드】 Infection, Case report, Coronavirus-2, fulminant,