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Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation

Published online by Cambridge University Press:  06 May 2022

Geraldo F. Busatto*
Affiliation:
Departamento e Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil Diretoria Executiva dos LIMs, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Adriana Ladeira de Araujo
Affiliation:
Diretoria Executiva dos LIMs, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
João Mauricio Castaldelli-Maia
Affiliation:
Departamento e Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil Departamento de Neurociências, Centro Universitário da Faculdade de Medicina do ABC, São Paulo, SP, Brasil
Rodolfo Furlan Damiano
Affiliation:
Departamento e Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Marta Imamura
Affiliation:
Departamento de Medicina Legal, Etica Medica e Medicina Social e do Trabalho, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Bruno F. Guedes
Affiliation:
Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Fabio de Rezende Pinna
Affiliation:
Departamento de Oftalmologia e Otorrinolaringologia, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Marcio Valente Yamada Sawamura
Affiliation:
Departamento de Radiologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Márcio C. Mancini
Affiliation:
Unidade de Obesidade e Síndrome Metabólica, Disciplina de Endocrinologia e Metabologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Katia R. da Silva
Affiliation:
Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Michelle L. Garcia
Affiliation:
Divisão de Pneumologia, Instituto do Coração, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
Nairo Sumita
Affiliation:
Departamento de Patologia Clínica, LIM/03 – Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
Andre Russowsky Brunoni
Affiliation:
Departamento de Clínica Médica, LIM/27 – Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
Alberto J. da Silva Duarte
Affiliation:
Departamento de Dermatologia, Laboratório de Dermatologia e Imunodeficiências, LIM-56, Faculdade de Medicina e Instituto de Medicina Tropical de São Paulo, São Paulo, SP, Brasil
Emmanuel A. Burdmann
Affiliation:
Departamento de Clínica Médica, LIM/12 – Laboratório de Pesquisa Básica em Doenças Renais, Disciplina de Nefrologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
Esper G. Kallas
Affiliation:
Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
Giovanni G. Cerri
Affiliation:
Departamento de Radiologia, Faculdade de Medicina, LIM/44, Laboratório de Ressonância Magnética em Neurorradiologia Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
Ricardo Nitrini
Affiliation:
Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Ricardo F. Bento
Affiliation:
Departamento de Oftalmologia e Otorrinolaringologia, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil Divisão de Otorrinolaringologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Vanderson Geraldo Rocha
Affiliation:
Serviço de Hematologia, Hemoterapia e Terapia Celular, Divisão de Clínica Médica I do ICHC, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Heraldo Possolo de Souza
Affiliation:
Departamento de Clínica Médica, Disciplina de Emergências Clínicas, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Euripedes C. Miguel
Affiliation:
Departamento e Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Carlos R. R. de Carvalho
Affiliation:
Divisão de Pneumologia, Instituto do Coração, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
Orestes V. Forlenza
Affiliation:
Departamento e Instituto de Psiquiatria, Laboratório de Neurociências – LIM-27, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
Linamara Rizzo Batistella
Affiliation:
Departamento de Medicina Legal, Etica Medica e Medicina Social e do Trabalho, Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brasil
*
Author for correspondence: Geraldo F. Busatto, E-mail: [email protected]

Abstract

Background

Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce.

Methods

We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6–11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment.

Results

The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215–0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123–0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities.

Conclusions

Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Type
Original Article
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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Footnotes

*

Equal contribution

**

The HCFMUSP COVID-19 Study Group is Eloisa Bonfá, Edivaldo M. Utiyama, Aluisio C. Segurado, Beatriz Perondi, Anna Miethke-Morais, Amanda C. Montal, Leila Harima, Solange R.G.Fusco, Marjorie F. Silva, Marcelo C. Rocha, Izabel Marcilio, Izabel Cristina Rios, Fabiane Yumi Ogihara Kawano, Maria Amélia de Jesus, Carolina Carmo, Clarice Tanaka, Julio F. M. Marchini, Juliana C Ferreira, Anna Sara Levin, Maura Salaroli Oliveira, Thaís Guimarães, Carolina dos Santos Lázari, Ester Sabino, Marcello M. C. Magri, Tarcisio E. P. Barros-Filho, Maria Cristina Peres Braido Francisco, Silvia Figueiredo Costa

This article has been updated since its original publication. A correction notice detailing the changes can be found here: https://doi.org/10.1017/S0033291722001799

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