Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series
Various authors have hypothesized carotid body (CB) involvement in Coronavirus Disease 2019 (COVID-19), through direct invasion or indirect effects by systemic stimuli (‘cytokine storm’, angiotensin-converting enzyme [ACE]1/ACE2 imbalance). However, empirical evidence is limited or partial. Here, we...
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| Format: | Article |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.736529/full |
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| author | Andrea Porzionato Aron Emmi Martina Contran Elena Stocco Silvia Riccetti Alessandro Sinigaglia Veronica Macchi Luisa Barzon Raffaele De Caro |
| author_facet | Andrea Porzionato Aron Emmi Martina Contran Elena Stocco Silvia Riccetti Alessandro Sinigaglia Veronica Macchi Luisa Barzon Raffaele De Caro |
| author_sort | Andrea Porzionato |
| collection | DOAJ |
| description | Various authors have hypothesized carotid body (CB) involvement in Coronavirus Disease 2019 (COVID-19), through direct invasion or indirect effects by systemic stimuli (‘cytokine storm’, angiotensin-converting enzyme [ACE]1/ACE2 imbalance). However, empirical evidence is limited or partial. Here, we present an integrated histopathological and virological analysis of CBs sampled at autopsy from four subjects (2 males and 2 females; age: >70 years old) who died of COVID-19. Histopathological, immunohistochemical and molecular investigation techniques were employed to characterize Severe Acute Respiratory Syndrome – Coronavirus 2 (SARS-CoV2) viral invasion and inflammatory reaction. SARS-CoV2 RNA was detected in the CBs of three cases through Real-Time Reverse Transcription Polymerase Chain Reaction (RT-PCR). In these cases, positive immunostaining for Nucleocapsid and Spike protein were also demonstrated, mainly at the level of large roundish cells consistent with type I cells, confirming direct CB invasion. In these cases, T lymphocytes showed focal aggregations in the CBs, suggestive of local inflammatory reaction. Blood congestion and microthrombosis were also found in one of the positive cases. Intriguingly, microthrombosis, blood congestion and microhaemorrages were also bilaterally detected in the CBs of the negative case, supporting the possibility of COVID-19 effects on the CB even in the absence of its direct invasion. SARS-CoV-2 direct invasion of the CB is confirmed through both immunohistochemistry and RT-PCR, with likely involvement of different cell types. We also reported histopathological findings which could be ascribed to local and/or systemic actions of SARS-CoV-2 and which could potentially affect chemoreception. |
| first_indexed | 2024-12-14T08:30:23Z |
| format | Article |
| id | doaj.art-6decc62ac60c4b6bb56ecdbff2d9a60c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T08:30:23Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6decc62ac60c4b6bb56ecdbff2d9a60c2022-12-21T23:09:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.736529736529Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case SeriesAndrea Porzionato0Aron Emmi1Martina Contran2Elena Stocco3Silvia Riccetti4Alessandro Sinigaglia5Veronica Macchi6Luisa Barzon7Raffaele De Caro8Department of Neuroscience, Section of Human Anatomy, University of Padova, Padova, ItalyDepartment of Neuroscience, Section of Human Anatomy, University of Padova, Padova, ItalyDepartment of Neuroscience, Section of Human Anatomy, University of Padova, Padova, ItalyDepartment of Neuroscience, Section of Human Anatomy, University of Padova, Padova, ItalyDepartment of Molecular Medicine, University of Padova, Padova, ItalyDepartment of Molecular Medicine, University of Padova, Padova, ItalyDepartment of Neuroscience, Section of Human Anatomy, University of Padova, Padova, ItalyDepartment of Molecular Medicine, University of Padova, Padova, ItalyDepartment of Neuroscience, Section of Human Anatomy, University of Padova, Padova, ItalyVarious authors have hypothesized carotid body (CB) involvement in Coronavirus Disease 2019 (COVID-19), through direct invasion or indirect effects by systemic stimuli (‘cytokine storm’, angiotensin-converting enzyme [ACE]1/ACE2 imbalance). However, empirical evidence is limited or partial. Here, we present an integrated histopathological and virological analysis of CBs sampled at autopsy from four subjects (2 males and 2 females; age: >70 years old) who died of COVID-19. Histopathological, immunohistochemical and molecular investigation techniques were employed to characterize Severe Acute Respiratory Syndrome – Coronavirus 2 (SARS-CoV2) viral invasion and inflammatory reaction. SARS-CoV2 RNA was detected in the CBs of three cases through Real-Time Reverse Transcription Polymerase Chain Reaction (RT-PCR). In these cases, positive immunostaining for Nucleocapsid and Spike protein were also demonstrated, mainly at the level of large roundish cells consistent with type I cells, confirming direct CB invasion. In these cases, T lymphocytes showed focal aggregations in the CBs, suggestive of local inflammatory reaction. Blood congestion and microthrombosis were also found in one of the positive cases. Intriguingly, microthrombosis, blood congestion and microhaemorrages were also bilaterally detected in the CBs of the negative case, supporting the possibility of COVID-19 effects on the CB even in the absence of its direct invasion. SARS-CoV-2 direct invasion of the CB is confirmed through both immunohistochemistry and RT-PCR, with likely involvement of different cell types. We also reported histopathological findings which could be ascribed to local and/or systemic actions of SARS-CoV-2 and which could potentially affect chemoreception.https://www.frontiersin.org/articles/10.3389/fimmu.2021.736529/fullcarotid bodyCOVID-19nervous systemsilent hypoxiaperipheral arterial chemoreceptorschemosensitivity |
| spellingShingle | Andrea Porzionato Aron Emmi Martina Contran Elena Stocco Silvia Riccetti Alessandro Sinigaglia Veronica Macchi Luisa Barzon Raffaele De Caro Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series Frontiers in Immunology carotid body COVID-19 nervous system silent hypoxia peripheral arterial chemoreceptors chemosensitivity |
| title | Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series |
| title_full | Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series |
| title_fullStr | Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series |
| title_full_unstemmed | Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series |
| title_short | Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series |
| title_sort | case report the carotid body in covid 19 histopathological and virological analyses of an autopsy case series |
| topic | carotid body COVID-19 nervous system silent hypoxia peripheral arterial chemoreceptors chemosensitivity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.736529/full |
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