A prevalência de transtorno mental comum neste grupo de pacientes pós-covid foi 32,2%, maior do que o relatado na população geral brasileira (26,8%).
This is a republication of the article below, complemented by an excerpt of the original publication.
Revista Medicina SA
11 de Fevereiro de 2022
Um estudo feito pela Faculdade de Medicina da Universidade de São Paulo (FMUSP) mostrou que pessoas que tiveram Covid-19 de forma moderada ou grave passaram a registrar maior incidência de transtornos psiquiátricos após a contaminação.
O artigo sobre a pesquisa foi publicado na revista científica General Hospital Psychiatry.
Foram avaliados 425 adultos, depois de seis a nove meses da alta hospitalar por causa da covid-19. Todos foram pacientes internados no Hospital das Clínicas da USP por pelo menos 24 horas, entre março e setembro de 2020.
Aqueles que precisaram de tratamento em unidade de terapia intensiva (UTI) foram considerados casos graves e os demais, moderados. Os pacientes foram submetidos a entrevista psiquiátrica estruturada, testes psicométricos e bateria cognitiva.
De acordo com o estudo, a prevalência de transtorno mental comum neste grupo de pacientes pós-covid foi 32,2%, maior do que o relatado na população geral brasileira (26,8%).
Quanto ao diagnóstico de depressão, houve prevalência de 8%, superior ao da população geral brasileira (em torno de 4% e 5%).
Transtornos de ansiedade generalizada estavam presentes em 14,1%, resultado também superior à prevalência na população geral brasileira (9,9%).
Segundo a pesquisa, os resultados psiquiátricos não foram associados a nenhuma variável clínica relacionada à gravidade da doença em fase aguda, ou seja, não foram mais preponderantes naqueles pacientes que apresentaram grau de inflamação maior, por exemplo.
“Os comprometimentos psiquiátricos e cognitivos observados a longo prazo após covid-19 moderada ou grave podem ser vistos como uma expressão dos efeitos do SARS-CoV-2 na homeostase [equilíbrio] cerebral ou uma representação de manifestações psiquiátricas inespecíficas secundárias à diminuição do estado geral de saúde”, diz o texto da pesquisa, que tem Rodolfo Damiano, médico residente do Instituto de Psiquiatria da Faculdade de Medicina da USP como primeiro autor.
Os resultados da pesquisa, que contou com apoio da Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp), podem ser vistos aqui. (Com informações da Agência Brasil)
Originally published at https://medicinasa.com.br on February 11, 2022.
ORIGINAL PUBLICATION
Post-COVID-19 psychiatric and cognitive morbidity: Preliminary findings from a Brazilian cohort study
Elsevier
General Hospital Psychiatry
5 February 2022
on behalf ofHCFMUSP COVID-19 Study Group1
Received 13 July 2021, Revised 31 December 2021, Accepted 4 January 2022, Available online 6 January 2022, Version of Record 5 February 2022.
Highlights
- This is the first study to capture psychiatric diagnosis in a large cohort of post-COVID-patients using clinical interview.
- We found a high prevalence of psychiatric diagnosis as well cognitive issues 6 to 9 months post-COVID-19.
- There was no relationship between disease severity at baseline and the degree of mental and cognitive impairment.
ABSTRACT
Objective
The present study aims to investigate the occurrence of psychiatric and cognitive impairments in a cohort of survivors of moderate or severe forms of COVID-19.
Method
425 adults were assessed 6 to 9 months after hospital discharge with a structured psychiatric interview, psychometric tests and a cognitive battery.
A large, multidisciplinary, set of clinical data depicting the acute phase of the disease, along with relevant psychosocial variables, were used to predict psychiatric and cognitive outcomes using the ‘Least Absolute Shrinkage and Selection Operator’ (LASSO) method.
Results
Diagnoses of ‘depression’, ‘generalized anxiety disorder’ and ‘post-traumatic stress disorder’ were established respectively in 8%, 15.5% and 13.6% of the sample.
After pandemic onset (i.e., within the previous year), the prevalence of ‘depression’ and ‘generalized anxiety disorder’ were 2.56% and 8.14%, respectively.
Memory decline was subjectively reported by 51.1% of the patients.
Psychiatric or cognitive outcomes were not associated with any clinical variables related to the severity of acute-phase disease, nor by disease-related psychosocial stressors.
Conclusions
This is the first study to access rates of psychiatric and cognitive morbidity in the long-term outcome after moderate or severe forms of COVID-19 using standardized measures.
As a key finding, there was no significant association between clinical severity in the acute-phase of SARS-CoV-2 infection and the neuropsychiatric impairment 6 to 9 months thereafter.
1. Introduction
There is an urgent need for a better characterization of the profile of acute and chronic psychiatric and neuropsychological morbidity among COVID-19 victims and the role played by multiple pathophysiological components related to disease severity/staging and individuals’ clinical characteristics.
Cross-sectional studies addressing the incidence of psychiatric and cognitive abnormalities in the acute and severe cases of SARS-CoV-2 infection highlight the occurrence of delirium, encephalopathy, cognitive impairment, insomnia, psychosis and mood symptoms [1].
Regarding chronic symptoms, longitudinal studies conducted in post-COVID-19 cohorts have presented preliminary evidence of a high prevalence of psychiatric symptoms in the ‘long phase’ of the disease, namely anxiety, depression, fatigue, and post-traumatic stress disorder (PTSD) [[2], [3], [4], [5], [6]], though recent studies indicated that these symptoms tend to wane in the following months [7].
These large longitudinal studies are important but fail in differentiating infected from non-infected individuals as well as patients with asymptomatic, mild, moderate, and severe cases, who might present with different phenomenological characteristics [8,9].
Psychiatric and cognitive morbidity following SARS-CoV-2 infection may emerge from multiple factors as part of what is being referred to as post-acute COVID-19 syndrome (PACS) or “long COVID” [10].
Psychosocial stress represents an important mechanism that predisposes COVID-19 victims to emotional suffering, some of whom will ultimately present with signs and symptoms of major psychiatric disorders [11].
However, recent evidence indicates that neuropsychiatric outcomes may also represent features of systemic and central nervous system (CNS) involvement in the pathophysiology of COVID-19, resulting largely from indirect mechanisms mediated by inflammation, hypercoagulability, vascular, and immunological pathways, in addition to possible direct invasion of the brain by the coronavirus [4,12].
According to current knowledge, the interaction of multiple COVID-19-related pathophysiological mechanisms disrupts brain homeostasis, causing dysfunctions/injuries that will ultimately present as symptoms of mental and cognitive impairment (‘neurocovid’) [13].
A recent perspective piece suggested that, in vulnerable populations (particularly the elderly), SARS-CoV-2 infection may hasten underlying brain pathologies and increase the risk of late-life cognitive decline and progression to dementia [14].
The available knowledge on the so-called ‘neurocovid’ hypothesis was largely built from the clinical analysis of case series and uncontrolled studies conducted amidst the pandemic.
In spite of the inherent methodological difficulties of carrying out research in this context, the current body of evidence about COVID-19-related neuropsychiatric morbidity does encourage the implementation of more refined symptom assessment protocols to address this matter in greater depth.
Most studies so far have methodological limitations, such as cross-sectional design [15] and lack of standardized SARS-CoV-2 infection determination [16] and lack of severity markers [17].
Furthermore, the assessment of the mental state has been generally based on small arrays of neuropsychiatric symptoms [18], frequently assessed by self-report questionnaires [19], electronic databases [20], or by the attending physician’s clinical impression [1], therefore restricted to dimensional or non-validated symptomatic scales [5,7,21].
Finally, most of the available literature was published in populations from Eastern and European countries, which may constrain the generalizability of findings [5].
The primary objective of the present study is to ascertain the mental and cognitive state of COVID-19 survivors after 6 to 9 months of the acute episode, with emphasis on the assessment of patients who recovered from moderate or severe forms of the disease requiring hospitalization, using a comprehensive protocol composed by objective and validated psychometric instruments.
As a secondary and exploratory goal, we determined the extent to which these impairments were correlated with the severity of the acute disease, as well as with the occurrence of stressful events related to the COVID-19 pandemic, trying to predict potential variables associated with a worse neuropsychiatric morbidity.
2. Methods
See the original publication
4. Discussion
The present study provides original data highlighting the high prevalence of neuropsychiatric impairment in the long-term outcome of moderate or severe forms of SARS-CoV-2 infection.
To the best of our knowledge, the objective assessment of mental state with the aid of validated diagnostic instruments is a relevant and original contribution in the characterization of psychiatric and cognitive impairments among COVID-19 survivors; most of the previous studies dedicated to the assessment of long-term post-COVID-19 neuropsychiatric morbidity were based solely on unstructured questionnaires, self-report tests, telephone-based interviews or other forms of remote assessment, yielding at best a preliminary overview of complaints and symptoms.
Moreover, studies that proposed to assess potential predictors of psychiatric and cognitive morbidity included only a few variables, most of them assessed retrospectively.
The protocol that we used in the present study was built to provide diagnostic classification and to depict a more detailed symptomatic profile of post-COVID-19 psychiatric and cognitive morbidity.
A comprehensive array of clinical and functional variables that had been previously tabulated during hospital treatment, along with a set of COVID-19 related psychosocial stressors, were used to evaluate the contribution of these acute-phase variables to the long-term psychiatric outcomes.
The CIS-R diagnoses of ‘common mental disorder’, ‘anxiety’ and ‘PTSD’ were highly prevalent.
Also, we found that roughly one-third of the new diagnoses of ‘depression’ and ‘obsessive-compulsive disorder’, and the majority of diagnoses of ‘generalized anxiety disorder’ were established within the previous year in our sample of post-COVID-19 survivors.
This is in line with previous studies that called attention to the high prevalence of mental health problems in the course of COVID-19 [26,27].
The prevalence of ‘common mental disorder’ in this post-COVID-19 cohort (32.2%) was higher than previously reported in the Brazilian general population (26.8%), as indicated by epidemiological studies using the CIS-R schedule, [28].
Regarding the CIS-R diagnosis of ‘depression’, prevalence in the present sample (8.0%) was higher than expected in epidemiological studies concerning high- and low-income countries (respectively 5.5% and 5.9%, 12-month prevalence), as well as in general Brazilian population using the same instrument (around 4 and 5%) [29].
The CIS-R diagnosis of ‘generalized anxiety disorder’ (GAD) in the present sample (14.1%) was considerably higher than the 12-month prevalence in the European general population (0.2–4.3%) [30], in Brazilian general population (9.9%) and in Brazilian individuals with coronary heart disease (10.2%), both using the same instrument [31].
A recent study using the same structured interview (CIS-R) in representative sample of Brazilian general population during COVID-19 pandemic found lower rates than reported in this manuscript, with 21.1% of common mental disorders, 2.8% of depressive disorders and 8% of anxiety disorders, highlighting high prevalence in our sample [32].
Even though the cross-sectional nature of the psychiatric data acquisition precludes the assessment of incidence rates, we were able to determine the prevalence of new psychiatric diagnoses.
Our data indicate a high prevalence of new diagnoses of ‘depression’, ‘generalized anxiety disorder’ and ‘obsessive compulsive disorder’, contrasting with the findings of a recent meta-analysis of longitudinal studies that found only a small increase on mental health issues among general population pre- and post-COVID-19 pandemic [33].
Noteworthy, our sample is older and represented by COVID-19 survivors, and therefore more prone to be clinically impaired.
We understand that the high proportion of new psychiatric diagnoses in our sample can be related to the severity of COVID-19 morbidity, but may also contain an indirect effect of controversial policies in Brazil during the COVID-19 crisis [34], given that the appropriateness of public policies has been shown to moderate mental health burden in the general population during COVID-19 pandemic [35].
The impact of the actual COVID-19 infection on new psychiatric diagnoses was challenged by a recent meta-analysis, although not controlling for the severity of the acute disease [36].
We found high rates of lifetime delusions (8.7%) and hallucinations (12.5%) in the present sample.
Even though there are some reports of psychotic symptoms following COVID-19 [37], there are several reports indicating high rates of lifetime psychotic symptoms in the general population, ranging from 7.2 to 12.5% [38,39], consistent with our findings.
In our study, ‘delusions of religious content’ accounted for a substantial proportion of the latter classification (6.15%), and we perceived that, in many such cases, non-delusional religious beliefs (e.g., acknowledging any form of spiritual interference or guidance as key to surviving the disease) could have led to an overestimation of this item.
Therefore, after withdrawing ‘delusions of religious content’ from the former estimate, the overall prevalence of delusions was downgraded to 6.35%.
Impairments in several cognitive domains were found in our sample, especially executive and attentional deficits.
Likewise, previous studies in COVID-19 survivors have pointed out to impairments in several cognitive domains in acute forms of the disease [4,40], particularly logical memory and executive functions (attention and cognitive flexibility), which were interpreted as possibly related to the systemic inflammatory process [40].
Long-term studies following patients with severe acute illnesses and acute respiratory distress syndrome point to cognitive decline and executive dysfunction as well [41,42].
Contrary to what we expected, cognitive morbidity after six months of SARS-CoV-2 infection was unrelated to any of the multiple clinical parameters relative to the acute phase of the disease, nor to any of psychiatric diagnoses that were established after six months of hospital discharge.
Disorientation was only associated with pre-existing dementia or stroke, presumably reflecting cognitive impairment prior to COVID-19.
Older age and disorientation (according to MMSE) were associated with worse performance in attention and verbal fluency tasks, and lower scores in verbal fluency were associated with frailty.
In a recent study, Jaywant et al. [43] evaluated cognitive impairment prior to hospital discharge in a cross-section of 57 inpatients recovering from severe COVID-19, and, similar to our findings, the authors found high rates of attention and executive dysfunction unrelated to clinical severity.
Conversely, Taquet et al. [20] in a large retrospective cohort study, found a positive association between disease severity and neuropsychiatric symptomatology using a large electronic health record.
The presence and severity of psychiatric manifestations were unrelated to two important psychosocial stressors (i.e., ‘death of a close relative’ or ‘financial loss’), nor to any of the multiple clinical parameters relative to the acute phase of the disease.
Psychosocial stressors [11] such as death of a close relative [44] or major financial loss [45] are reputed to be powerful triggers of psychiatric morbidity; however, these variables were not associated with a worse neuropsychiatric outcome in our sample.
In the absence of any such associations between risk factors and observed outcomes, psychiatric and cognitive impairments observed in the long-term after moderate or severe COVID-19 could be viewed either as an expression of SARS-CoV-2 effects on brain homeostasis or a representation of non-specific psychiatric manifestations secondary to diminished general health status, given that these disorders are correlated with general health status regardless of the cause of diminished general health [46].
Surprisingly though, patients who had been submitted to hemodialysis during ICU treatment for COVID-19 performed better on the verbal fluency test.
We do not have a prompt interpretation for this putative ‘protective’ effect of hemodialysis on this specific cognitive domain, although the beneficial effect of dialysis on the clearance of systemic toxins could be regarded as advantageous in relation to severely ill patients who remained at pre-dialytic states. Previous studies have shown that individuals discharged from ICU [47] (especially those with acute respiratory distress syndrome) may present with symptoms compatible with post-intensive care syndrome (PICS) [48], which consists in a combination of psychological, physical and cognitive impairments following conditions that did require critical care, and may persist for up to five years after ICU discharge [49].
We must also acknowledge the limitations of the present study.
First, the assessment of psychiatric and cognitive impairment in this cohort was performed after 6–9 months of the acute episode, in the absence of a similar protocol implemented at baseline, and thus precludes the characterization of changes secondary to this viral disease. However, it is noteworthy that a myriad of detailed information regarding clinical, laboratory and supplementary tests were accessible at baseline.
Second, selection bias might remove relevant cases from the study sample, given that patients with more severe consequences of the disease may be less prone to accept enrolment to the study and/or to comply with the procedures. Regarding psychiatric diagnoses, we acknowledge that the CIS-R interview focuses predominantly on mood and affective symptoms, without covering other relevant psychiatric domains. Because of that, we tried to buffer our assessment battery with other questionnaires and psychometric tests. In this regard, the assessment of psychotic symptoms based on the SCID-5-RV (Module B, Psychotic and Associated symptoms) may have been too specific to be implemented in a non-psychiatric sample. Even though all raters were trained for reliability, it is plausible that the lack of experience in the assessment of psychotic patients may have biased the completion of this questionnaire, particularly among less educated patients, to whom culture-bound and religious beliefs may have influenced their responses, causing the over-rating of psychotic symptoms.
Also, we did not include pre-existing psychiatric illness in our analysis due to lack of availability in the current dataset, though we plan to include this parameter in future analyses.
Furthermore, comparison of these results to general population prevalence rather than to the prevalence of these conditions in other patients recovering from serious illness limits one’s ability to assess the specificity of these findings. Furthermore, the category of ‘new diagnosis’ might be biased by memory recall bias.
Finally, 6 patients with high clinical suspicion of COVID-19, but without laboratory confirmation by PCR, were included. These individuals had been admitted as in-patients within the first 6 weeks after the initial preparation of HCFMUSP as a COVID-only facility, and the decision to include them was based on the fact that the in-hospital RT-PCR testing setup was not yet fully operational at that time. Nonetheless, the clinical picture of these cases was highly compatible with COVID-19 and they were treated as such throughout hospitalization.
In summary, we found a high prevalence of psychiatric and cognitive impairments following SARS-CoV-2 infection, specifically common mental disorders, depression, anxiety, PTSD, executive and attentional cognitive impairments.
These deficits seem unrelated to psychosocial stressors or clinical risk factors documented in the acute-stage of COVID-19.
The present findings should encourage longitudinal studies addressing changes in mental and cognitive state among COVID-19 survivors across distinct ranges of severity.
Received 13 July 2021, Revised 31 December 2021, Accepted 4 January 2022, Available online 6 January 2022, Version of Record 5 February 2022.
References & additional information
See the original publication
About the authors & authors information
on behalf ofHCFMUSP COVID-19 Study Group1
a Departamento e Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brazil
b Departamento de Neurologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, SP, Brazil
c Centro de Pesquisas Clínicas e Epidemiológicas, Hospital Universitário, Universidade de São Paulo, São Paulo, Brazil
d Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
e Departamento e Instituto de Psiquiatria, Laboratory of Neurosciences (LIM-27), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
f Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
g Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
h Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States
i Department of Psychiatry, Harvard Medical School, Boston, MA, United States
Received 13 July 2021, Revised 31 December 2021, Accepted 4 January 2022, Available online 6 January 2022, Version of Record 5 February 2022.
Originally published at https://www.sciencedirect.com
