RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies
The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.824967/full |
| _version_ | 1798024857183584256 |
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| author | Tamara Caniego-Casas Tamara Caniego-Casas Tamara Caniego-Casas Laura Martínez-García Laura Martínez-García Laura Martínez-García Marina Alonso-Riaño Marina Alonso-Riaño Marina Alonso-Riaño David Pizarro David Pizarro David Pizarro Irene Carretero-Barrio Irene Carretero-Barrio Nilda Martínez-de-Castro Ignacio Ruz-Caracuel Raúl de Pablo Raúl de Pablo Raúl de Pablo Ana Saiz Ana Saiz Rosa Nieto Royo Ana Santiago Marta Rosas Marta Rosas José L. Rodríguez-Peralto José L. Rodríguez-Peralto José L. Rodríguez-Peralto Belén Pérez-Mies Belén Pérez-Mies Belén Pérez-Mies Belén Pérez-Mies Juan C. Galán Juan C. Galán Juan C. Galán José Palacios José Palacios José Palacios José Palacios |
| author_facet | Tamara Caniego-Casas Tamara Caniego-Casas Tamara Caniego-Casas Laura Martínez-García Laura Martínez-García Laura Martínez-García Marina Alonso-Riaño Marina Alonso-Riaño Marina Alonso-Riaño David Pizarro David Pizarro David Pizarro Irene Carretero-Barrio Irene Carretero-Barrio Nilda Martínez-de-Castro Ignacio Ruz-Caracuel Raúl de Pablo Raúl de Pablo Raúl de Pablo Ana Saiz Ana Saiz Rosa Nieto Royo Ana Santiago Marta Rosas Marta Rosas José L. Rodríguez-Peralto José L. Rodríguez-Peralto José L. Rodríguez-Peralto Belén Pérez-Mies Belén Pérez-Mies Belén Pérez-Mies Belén Pérez-Mies Juan C. Galán Juan C. Galán Juan C. Galán José Palacios José Palacios José Palacios José Palacios |
| author_sort | Tamara Caniego-Casas |
| collection | DOAJ |
| description | The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9–108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of <2 weeks, but in none of the 23 adult patients with an illness duration of >2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease. |
| first_indexed | 2024-04-11T18:10:33Z |
| format | Article |
| id | doaj.art-1f536eeb67b6488d9727266775fbb218 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-11T18:10:33Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-1f536eeb67b6488d9727266775fbb2182022-12-22T04:10:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-01-011310.3389/fmicb.2022.824967824967RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of AutopsiesTamara Caniego-Casas0Tamara Caniego-Casas1Tamara Caniego-Casas2Laura Martínez-García3Laura Martínez-García4Laura Martínez-García5Marina Alonso-Riaño6Marina Alonso-Riaño7Marina Alonso-Riaño8David Pizarro9David Pizarro10David Pizarro11Irene Carretero-Barrio12Irene Carretero-Barrio13Nilda Martínez-de-Castro14Ignacio Ruz-Caracuel15Raúl de Pablo16Raúl de Pablo17Raúl de Pablo18Ana Saiz19Ana Saiz20Rosa Nieto Royo21Ana Santiago22Marta Rosas23Marta Rosas24José L. Rodríguez-Peralto25José L. Rodríguez-Peralto26José L. Rodríguez-Peralto27Belén Pérez-Mies28Belén Pérez-Mies29Belén Pérez-Mies30Belén Pérez-Mies31Juan C. Galán32Juan C. Galán33Juan C. Galán34José Palacios35José Palacios36José Palacios37José Palacios38Pathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainCIBERONC, Instituto de Salud Carlos III, Madrid, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainMicrobiology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainCentro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Madrid, SpainPathology Department, Hospital Universitario 12 de Octubre, Madrid, SpainInstituto 12 de Octubre for Health Research, Madrid, SpainFaculty of Medicine, Complutense University, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainCIBERONC, Instituto de Salud Carlos III, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainFaculty of Medicine, University of Alcalá, Alcalá de Henares, Spain0Anaesthesiology and Surgical Critical Care Department, Hospital Universitario Ramón y Cajal, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainFaculty of Medicine, University of Alcalá, Alcalá de Henares, Spain1Medical Intensive Care Unit, Hospital Universitario Ramón y Cajal, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainFaculty of Medicine, University of Alcalá, Alcalá de Henares, Spain2Respiratory Department, Hospital Universitario Ramón y Cajal, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainPathology Department, Hospital Universitario 12 de Octubre, Madrid, SpainInstituto 12 de Octubre for Health Research, Madrid, SpainFaculty of Medicine, Complutense University, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainCIBERONC, Instituto de Salud Carlos III, Madrid, SpainFaculty of Medicine, University of Alcalá, Alcalá de Henares, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainMicrobiology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainCentro de Investigación Biomédica en Red en Epidemiología y Salud Pública, Madrid, SpainPathology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainInstituto Ramón y Cajal for Health Research (IRYCIS), Madrid, SpainCIBERONC, Instituto de Salud Carlos III, Madrid, SpainFaculty of Medicine, University of Alcalá, Alcalá de Henares, SpainThe exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9–108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of <2 weeks, but in none of the 23 adult patients with an illness duration of >2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease.https://www.frontiersin.org/articles/10.3389/fmicb.2022.824967/fullCOVID-19viral persistanceautopsyRNAimmunosuprression |
| spellingShingle | Tamara Caniego-Casas Tamara Caniego-Casas Tamara Caniego-Casas Laura Martínez-García Laura Martínez-García Laura Martínez-García Marina Alonso-Riaño Marina Alonso-Riaño Marina Alonso-Riaño David Pizarro David Pizarro David Pizarro Irene Carretero-Barrio Irene Carretero-Barrio Nilda Martínez-de-Castro Ignacio Ruz-Caracuel Raúl de Pablo Raúl de Pablo Raúl de Pablo Ana Saiz Ana Saiz Rosa Nieto Royo Ana Santiago Marta Rosas Marta Rosas José L. Rodríguez-Peralto José L. Rodríguez-Peralto José L. Rodríguez-Peralto Belén Pérez-Mies Belén Pérez-Mies Belén Pérez-Mies Belén Pérez-Mies Juan C. Galán Juan C. Galán Juan C. Galán José Palacios José Palacios José Palacios José Palacios RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies Frontiers in Microbiology COVID-19 viral persistance autopsy RNA immunosuprression |
| title | RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies |
| title_full | RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies |
| title_fullStr | RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies |
| title_full_unstemmed | RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies |
| title_short | RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies |
| title_sort | rna sars cov 2 persistence in the lung of severe covid 19 patients a case series of autopsies |
| topic | COVID-19 viral persistance autopsy RNA immunosuprression |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.824967/full |
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