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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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. |
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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><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0255950</identifier><identifier>PMID: 34506501</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2021-09, Vol.16 (9), p.e0255950-e0255950</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Santana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Santana et al 2021 Santana et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-de95e5352725bcb09c99d837ace453b2bbee96547268849f6de92450d845a7ba3</citedby><cites>FETCH-LOGICAL-c692t-de95e5352725bcb09c99d837ace453b2bbee96547268849f6de92450d845a7ba3</cites><orcidid>0000-0002-6464-3035 ; 0000-0001-6703-9565 ; 0000-0002-5398-7414 ; 0000-0002-6007-7128 ; 0000-0001-7849-6112 ; 0000-0001-7720-0869</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432786/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432786/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34506501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tan, Wenbin</contributor><creatorcontrib>Santana, Monique Freire</creatorcontrib><creatorcontrib>Frank, Carlos Henrique Michiles</creatorcontrib><creatorcontrib>Almeida, Taynná Vernalha Rocha</creatorcontrib><creatorcontrib>Jeronimo, Christiane Maria Prado</creatorcontrib><creatorcontrib>de Araújo Pinto, Rebecca Augusta</creatorcontrib><creatorcontrib>Martins, Yasmin Ferreira</creatorcontrib><creatorcontrib>de Farias, Maria Eduarda Leão</creatorcontrib><creatorcontrib>Dutra, Bruna Guimarães</creatorcontrib><creatorcontrib>Brito-Sousa, José Diego</creatorcontrib><creatorcontrib>Baía-da-Silva, Djane Clarys</creatorcontrib><creatorcontrib>Xavier, Mariana Simão</creatorcontrib><creatorcontrib>Lacerda, Marcus Vinicius Guimarães</creatorcontrib><creatorcontrib>Almeida Val, Fernando Fonseca</creatorcontrib><creatorcontrib>Monteiro, Gisely Cardoso</creatorcontrib><creatorcontrib>Sampaio, Vanderson de Souza</creatorcontrib><creatorcontrib>Monteiro, Wuelton Marcelo</creatorcontrib><creatorcontrib>Ferreira, Luiz Carlos de Lima</creatorcontrib><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</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</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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Henrique Michiles</creatorcontrib><creatorcontrib>Almeida, Taynná Vernalha Rocha</creatorcontrib><creatorcontrib>Jeronimo, Christiane Maria Prado</creatorcontrib><creatorcontrib>de Araújo Pinto, Rebecca Augusta</creatorcontrib><creatorcontrib>Martins, Yasmin Ferreira</creatorcontrib><creatorcontrib>de Farias, Maria Eduarda Leão</creatorcontrib><creatorcontrib>Dutra, Bruna Guimarães</creatorcontrib><creatorcontrib>Brito-Sousa, José Diego</creatorcontrib><creatorcontrib>Baía-da-Silva, Djane Clarys</creatorcontrib><creatorcontrib>Xavier, Mariana Simão</creatorcontrib><creatorcontrib>Lacerda, Marcus Vinicius Guimarães</creatorcontrib><creatorcontrib>Almeida Val, Fernando Fonseca</creatorcontrib><creatorcontrib>Monteiro, Gisely Cardoso</creatorcontrib><creatorcontrib>Sampaio, Vanderson de Souza</creatorcontrib><creatorcontrib>Monteiro, Wuelton Marcelo</creatorcontrib><creatorcontrib>Ferreira, Luiz Carlos de 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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> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2021-09, Vol.16 (9), p.e0255950-e0255950 |
issn | 1932-6203 1932-6203 |
language | eng |
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source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
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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