Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19

The study “Persistent SARS-CoV-2 Infection in Patients Seemingly Recovered from COVID-19,” conducted by Bussani et al., was focused on understanding the pathology of COVID-19 in patients who appeared to have recovered from the acute infection but continued to deteriorate clinically and eventually died.

The key findings and methodology of the study are as follows:

  1. Study Overview: The study involved post-mortem analyses of 27 patients who had seemingly recovered from COVID-19. These patients had been PCR-negative for SARS-CoV-2 RNA for periods ranging from 11 to 300 days (average: 105.5 days), with some remaining negative for over 9 months. Despite this, they experienced progressive worsening of their clinical conditions​​.
  2. Methodology:
    • Patient Cohort: The study was conducted at the University Hospital and School of Medicine in Trieste, Italy. The patients analyzed had histories of COVID-19 of varying severities. Clinical data including age, gender, comorbidities, and therapies were collected​​.
    • Diagnostic Tests: PCR tests were performed on combined oropharyngeal and nasopharyngeal swabs, with a quantitative real-time PCR kit used for SARS-CoV-2 genome quantification​​.
    • Histological Analysis: Samples were fixed, embedded in paraffin, and stained for analysis. The severity of pneumonia and the extent of lung fibrosis were evaluated on a defined scale. Cartilage alterations were also classified​​.
  3. Key Findings:
    • Lung Pathology Similar to Acute COVID-19: Many patients exhibited lung pathology akin to that observed in acute COVID-19 cases, including interstitial pneumonia, extensive fibrotic substitution, thrombosis, vasculitis, and abnormalities in respiratory epithelium​​.
    • Viral Persistence in Specific Lung Cells: The study found that, despite PCR test negativity, there was evidence of SARS-CoV-2 infection in specific lung cells, particularly bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. This was confirmed using immunohistochemistry for spike and nucleocapsid proteins, and RT-PCR amplification in tissue lysates for viral RNA​​.
    • Implications for Long COVID: The presence of virus-infected cells, despite apparent molecular remission, suggests a potential pathogenic role for these cells in the phenomenon of long COVID, where patients continue to experience symptoms long after clearing the acute phase of the infection​​.
  4. Pathogenic Relevance: The study noted that the presence of spike protein on cell surfaces could have pathogenic relevance, affecting immune responses and promoting a pro-coagulant phenotype, potentially explaining the prolonged symptoms and deterioration in these patients​​.
  5. Support and Acknowledgments: The study was supported by various grants, including those from the Ministero della Salute Government of Italy and King’s College London. Several individuals were acknowledged for their technical support in autopsies, histology, and immunohistochemistry​​.

In summary, this study provides critical insights into the persistence of SARS-CoV-2 in certain lung cells of patients who appear to have recovered from COVID-19, contributing to the understanding of long COVID and its pathology.

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