Hemorrhagic and thrombotic manifestations in the central nervous system in COVID-19: A large observational study in the Brazilian Amazon with a complete autopsy series

SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Neve...

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Veröffentlicht in:PloS one 2021-09, Vol.16 (9), p.e0255950-e0255950
Hauptverfasser: Santana, Monique Freire, Frank, Carlos Henrique Michiles, Almeida, Taynná Vernalha Rocha, Jeronimo, Christiane Maria Prado, de Araújo Pinto, Rebecca Augusta, Martins, Yasmin Ferreira, de Farias, Maria Eduarda Leão, Dutra, Bruna Guimarães, Brito-Sousa, José Diego, Baía-da-Silva, Djane Clarys, Xavier, Mariana Simão, Lacerda, Marcus Vinicius Guimarães, Almeida Val, Fernando Fonseca, Monteiro, Gisely Cardoso, Sampaio, Vanderson de Souza, Monteiro, Wuelton Marcelo, Ferreira, Luiz Carlos de Lima
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container_issue 9
container_start_page e0255950
container_title PloS one
container_volume 16
creator Santana, Monique Freire
Frank, Carlos Henrique Michiles
Almeida, Taynná Vernalha Rocha
Jeronimo, Christiane Maria Prado
de Araújo Pinto, Rebecca Augusta
Martins, Yasmin Ferreira
de Farias, Maria Eduarda Leão
Dutra, Bruna Guimarães
Brito-Sousa, José Diego
Baía-da-Silva, Djane Clarys
Xavier, Mariana Simão
Lacerda, Marcus Vinicius Guimarães
Almeida Val, Fernando Fonseca
Monteiro, Gisely Cardoso
Sampaio, Vanderson de Souza
Monteiro, Wuelton Marcelo
Ferreira, Luiz Carlos de Lima
description SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.
doi_str_mv 10.1371/journal.pone.0255950
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Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. 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Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibiotics</subject><subject>Autopsies</subject><subject>Autopsy</subject><subject>Biology and Life Sciences</subject><subject>Brazil - epidemiology</subject><subject>Central nervous system</subject><subject>Central Nervous System - pathology</subject><subject>Cerebrovascular disease</subject><subject>Comorbidity</subject><subject>Confidence intervals</subject><subject>Consciousness</subject><subject>Coronaviruses</subject><subject>Corticosteroids</subject><subject>COVID-19</subject><subject>COVID-19 - epidemiology</subject><subject>Diabetes mellitus</subject><subject>Diagnosis</subject><subject>Disease transmission</subject><subject>Female</subject><subject>Health 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risks</topic><topic>Hemorrhage</topic><topic>Hemorrhage - epidemiology</topic><topic>Humans</topic><topic>Infections</topic><topic>Laboratories</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Methods</topic><topic>Middle Aged</topic><topic>Nervous system</topic><topic>Neurologic manifestations of general diseases</topic><topic>Observational studies</topic><topic>Pathology</topic><topic>Patients</topic><topic>Polymerase chain reaction</topic><topic>Respiratory diseases</topic><topic>Risk assessment</topic><topic>Risk factors</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Statistical analysis</topic><topic>Statistics</topic><topic>Subarachnoid hemorrhage</topic><topic>Thrombosis - epidemiology</topic><topic>Viral diseases</topic><topic>Viruses</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Santana, Monique Freire</creatorcontrib><creatorcontrib>Frank, Carlos 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&amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Santana, Monique Freire</au><au>Frank, Carlos Henrique Michiles</au><au>Almeida, Taynná Vernalha Rocha</au><au>Jeronimo, Christiane Maria Prado</au><au>de Araújo Pinto, Rebecca Augusta</au><au>Martins, Yasmin Ferreira</au><au>de Farias, Maria Eduarda Leão</au><au>Dutra, Bruna Guimarães</au><au>Brito-Sousa, José Diego</au><au>Baía-da-Silva, Djane Clarys</au><au>Xavier, Mariana Simão</au><au>Lacerda, Marcus Vinicius Guimarães</au><au>Almeida Val, Fernando Fonseca</au><au>Monteiro, Gisely Cardoso</au><au>Sampaio, Vanderson de Souza</au><au>Monteiro, Wuelton Marcelo</au><au>Ferreira, Luiz Carlos de Lima</au><au>Tan, Wenbin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hemorrhagic and thrombotic manifestations in the central nervous system in COVID-19: A large observational study in the Brazilian Amazon with a complete autopsy series</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-09-10</date><risdate>2021</risdate><volume>16</volume><issue>9</issue><spage>e0255950</spage><epage>e0255950</epage><pages>e0255950-e0255950</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34506501</pmid><doi>10.1371/journal.pone.0255950</doi><tpages>e0255950</tpages><orcidid>https://orcid.org/0000-0002-6464-3035</orcidid><orcidid>https://orcid.org/0000-0001-6703-9565</orcidid><orcidid>https://orcid.org/0000-0002-5398-7414</orcidid><orcidid>https://orcid.org/0000-0002-6007-7128</orcidid><orcidid>https://orcid.org/0000-0001-7849-6112</orcidid><orcidid>https://orcid.org/0000-0001-7720-0869</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
Aged, 80 and over
Antibiotics
Autopsies
Autopsy
Biology and Life Sciences
Brazil - epidemiology
Central nervous system
Central Nervous System - pathology
Cerebrovascular disease
Comorbidity
Confidence intervals
Consciousness
Coronaviruses
Corticosteroids
COVID-19
COVID-19 - epidemiology
Diabetes mellitus
Diagnosis
Disease transmission
Female
Health risks
Hemorrhage
Hemorrhage - epidemiology
Humans
Infections
Laboratories
Male
Medicine and Health Sciences
Methods
Middle Aged
Nervous system
Neurologic manifestations of general diseases
Observational studies
Pathology
Patients
Polymerase chain reaction
Respiratory diseases
Risk assessment
Risk factors
Severe acute respiratory syndrome coronavirus 2
Statistical analysis
Statistics
Subarachnoid hemorrhage
Thrombosis - epidemiology
Viral diseases
Viruses
Young Adult
title Hemorrhagic and thrombotic manifestations in the central nervous system in COVID-19: A large observational study in the Brazilian Amazon with a complete autopsy series
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