Persistent and fatal severe acute respiratory syndrome coronavirus 2 infection in a patient with severe hypogammaglobulinemia: a case report

Abstract

Background: Viruses are constantly changing as a result of mutations, and new viral variants are expected to appear over time. The virus that causes coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, is not excluded from this condition. Patients with some types of immunodeficiency have been reported to experience symptoms that vary from mild to severe, or even death, after being infected with severe acute respiratory syndrome coronavirus 2. We report a case of a woman with severe hypogammaglobulinemia who developed a prolonged and fatal severe acute respiratory syndrome coronavirus 2 infection.

Case presentation: A 60-year-old mestizo female with a previous history of severe hypogammaglobulinemia manifested by recurrent pulmonary infections and follicular bronchiolitis. She received a monthly treatment of intravenous immunoglobulins and was admitted after report of a neurological manifestation related to a left thalamic inflammatory lesion, for a duration of 2 weeks of hospitalization, indicated for the study of her neurological condition, including brain biopsy. Both on admission and 1 week later, nasopharyngeal polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 were performed and reported negative. In the third week of hospitalization, she developed pulmonary symptoms, and a positive test result for severe acute respiratory syndrome coronavirus 2 was evidenced. On Day 3, the patients' condition worsened as the infection progressed to respiratory failure and required mechanical ventilation. On Day 8 after the coronavirus disease 2019 diagnosis, the polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 showed persistent detection of the virus. Various bacterial coinfections, including Klebsiella pneumoniae and Enterobacter cloacae, were diagnosed and treated. On Day 35, her pulmonary symptoms worsened, and the results of the severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test remained positive. On Day 36, despite all the respiratory support, the patient died. The severe acute respiratory syndrome coronavirus 2 virus was sequenced at the beginning and 8 days after the onset of the disease, and the strain, without obvious mutations in the gene that encodes spike protein, was identified.

Conclusions: This clinical case showed persistent severe acute respiratory syndrome coronavirus 2 detection after 35 days of infection in a patient with severe hypogammaglobulinemia. The sequencing of the virus showed no mutations on the spike protein at 8 days, indicating that, in this case, the persistence of the viral detection was associated with immunodeficiency instead of changes in the viral components.

Keywords: COVID-19; Immunodeficiency; Mutations; Variants.

Fig. 1

Timeline of persistent COVID-19-related lung infection in a woman with severe hypogammaglobulinemia. Lung x-ray: A Extensive bilateral mixed opacities. Subpleural alveolar patches in both lungs. B Diffusely distributed mixed opacities with alveolar foci leading to consolidation in the left retrocardiac region. C Mixed opacities with bilateral patchy distribution with alveolar foci in both lower lobes and a tendency toward consolidation in the left retrocardiac region. D Diffuse mixed reticular and alveolar opacities, with areas of bilateral basal consolidation. Effacement of the right costophrenic angle, probably secondary to consolidation. PaFi arterial oxygen pressure/inspired oxygen fraction, RT–PCR reverse transcription-polymerase chain reaction

Fig. 2

SARS-CoV-2 genomic map. A Consensus mutations in the two sequenced samples. B All nucleotide substitutions (NT) are shown. Amino acid substitutions (AAs) are indicated for all nonsynonymous substitutions. ORF open reading frame, S spike protein, M membrane protein E, envelope protein, N nucleocapsid protein, NSP nonstructural protein