Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC jFJ5cmgvvxYxHVLQTNK6fXd S0066-782X2023000500204 00204 10.36660/abc.20230282 Minieditorial O Impacto Clínico dos Sintomas Cardiovasculares na Síndrome Pós-Aguda de COVID-19 0000-0001-7668-4224 Dutra Giovanni Possamai 1 0000-0001-7443-7270 Gomes Bruno Ferraz de Oliveira 1 2 Hospital Barra D’Or Rio de Janeiro RJ Brasil Hospital Barra D’Or, Rio de Janeiro, RJ – Brasil Universidade Federal do Rio de Janeiro Rio de Janeiro RJ Brasil Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ – Brasil Correspondência: Bruno Ferraz de Oliveira Gomes • Rede D’Or Sao Luiz – Cardiologia – Av. Ayrton Senna, 3079. CEP 22775-002, Rio de Janeiro, RJ – Brasil E-mail: drbrunoferraz@gmail.com 16 06 2023 05 2023 120 5 e20230282 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. COVID-19 Pandemia Mortalidade Comorbidade Doenças Cardiovasculares Saúde Pública Doença Cardiopulmar

A pandemia de COVID-19 tem impactado intensamente a vida das pessoas em todo o mundo, gerando, além de alta mortalidade, alta morbidade tardia e afetando negativamente os sistemas de saúde, permanecendo um significativo desafio global na atualidade. Em fevereiro de 2023, os registros da Organização Mundial da Saúde apontam para mais de 756 milhões de casos confirmados e aproximadamente 6.845.000 mortes. Até o referido mês, foram notificados aproximadamente 36.961.000 casos no Brasil, com cerca de 698.000 mortes. Considerando os desafios substanciais relacionados à comorbidade entre doença cardíaca e COVID-19, que vão além da fase aguda da doença, são necessários mais estudos para abordar de forma abrangente a alta carga de sintomas cardiopulmonares. Essas investigações devem ser cuidadosamente planejadas, considerando custo-efetividade e benefícios clínicos para os pacientes para minimizar as desigualdades na atenção à saúde. Além disso, é essencial otimizar o cuidado social e mental dos pacientes. O envolvimento cardiopulmonar na COVID-19 continua a representar um grande desafio de saúde pública.1 , 2

O estudo de Kalil-Filho et al.,3 incluiu 480 sobreviventes após internação por COVID-19 e avaliou as características associadas à ocorrência de sintomas cardiopulmonares e, principalmente, síndrome pós-aguda de COVID-19 (PACS).3 Foi uma amostra com predominância de homens, obesos e com comorbidades como hipertensão, diabetes e dislipidemia. Quase um quarto dos pacientes necessitou de internação em terapia intensiva e apenas 12,2% necessitaram de suporte ventilatório mecânico. A prevalência de algum dos sintomas foi menor (32,1%) do que a encontrada na literatura, assim como a PACS relacionada a sintomas cardiopulmonares (16,3%). Notavelmente, quase dois terços da população que realizou tomografia (n=122) não demonstrou envolvimento pulmonar. Assim, observamos que a população analisada apresentou menor grau de gravidade relacionado ao COVID-19, justificando a menor prevalência de sintomas.

A síndrome pós-COVID que afeta alguns pacientes após um evento agudo de COVID-19 tem várias definições. Essa síndrome é geralmente considerada em pacientes que permanecem com sintomas após 1 a 3 meses.4 Os sintomas mais comuns, relatados em vários estudos, são fadiga, dispneia e distúrbios do sono.5 No estudo de Kalil-Filho,3 o sintoma mais prevalente foi o cansaço, presente em quase metade da população. Sintomas como dispneia e tosse foram menos prevalentes e podem estar associados à menor gravidade desses pacientes.

As variáveis mais associadas aos sintomas cardiopulmonares foram tempo de internação, necessidade de unidade de terapia intensiva (UTI) e ventilação mecânica, presença de polineuropatia de doença crítica e níveis de proteína C-reativa (PCR). Mahmud et al. encontraram resultados semelhantes.6 Neste estudo, as variáveis associadas à síndrome pós-COVID foram: sexo feminino, duração da doença, positividade do teste após 14 dias e COVID-19 grave. Em pacientes de maior gravidade, espera-se maior ativação da cascata inflamatória e indução do sistema trombótico,7 justificando assim o maior risco de manutenção dos sintomas a longo prazo.

O impacto dos sintomas cardiopulmonares também foi avaliado neste estudo. Pacientes sintomáticos apresentaram pior qualidade de vida e maior prevalência de ansiedade, depressão e transtorno de estresse pós-traumático (TEPT). Aiyegbusi et al.,8 mostraram que quase 70% dos pacientes apresentavam algum grau de limitação física após 6 meses de internação. Da mesma forma, mostrou que um quarto dos pacientes apresentava sintomas moderados a graves de TEPT. Esse diagnóstico foi mais comum em mulheres e pacientes com história de doença psiquiátrica.8 Ansiedade e depressão foram frequentes neste estudo, demonstrando a relevância do estudo de Kalil-Filho.3

Por fim, na análise multivariada, observamos que as variáveis independentes relacionadas ao diagnóstico de PACS foram sexo feminino, trombose venosa profunda, níveis de troponina e proteína C-reativa e depressão. Esses achados reforçam a importância da magnitude da resposta inflamatória e trombótica do COVID-19 no surgimento de sintomas a longo prazo.

A pandemia de COVID-19 teve um impacto significativo na saúde pública global, com alta mortalidade e morbidade tardia, incluindo a ocorrência de sintomas cardiopulmonares. Este estudo, portanto, leva à reflexão sobre a necessidade de investigações abrangentes para abordar sua alta frequência, considerando o custo-efetividade e os benefícios clínicos para os pacientes para minimizar as desigualdades na assistência à saúde. Os sintomas cardiopulmonares pós- COVID são multifatoriais e requerem uma abordagem multidisciplinar.

Referências 1. De Oliveira GMM, Pinto F. Cardiac Involvement in COVID-19: A Matter Close to the Heart; Int J Cardiovasc Sci. 2023; 36:e20230024 De Oliveira GMM Pinto F Cardiac Involvement in COVID-19: A Matter Close to the Heart Int J Cardiovasc Sci 2023 36 e20230024 2. World Health Organization. WHO Coronavirus (COVID-19) Dashboard [Internet]. Geneva: World Health Organization; 2023 [cited 2023 Feb 17]. Available from: https://covid19.who.int/ World Health Organization WHO Coronavirus (COVID-19) Dashboard Internet Geneva World Health Organization 2023 cited 2023 Feb 17 https://covid19.who.int/ 3. Kalil-Filho R, Saretta R, Franci A, Baracioli LM, Galas FRBG, Gil JS, et al. Sintomas Cardiopulmonares Pós-COVID-19: Preditores e Características de Imagem de Pacientes após a Alta Hospitalar. Arq Bras Cardiol. 2023; 120(5):e20220642. DOI: https://doi.org/10.36660/abc.20220642 Kalil-Filho R Saretta R Franci A Baracioli LM Galas FRBG Gil JS et al Sintomas Cardiopulmonares Pós-COVID-19: Preditores e Características de Imagem de Pacientes após a Alta Hospitalar Arq Bras Cardiol 2023 120 5 e20220642 https://doi.org/10.36660/abc.20220642 4. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond).2021;53(10):737-54. doi: 10.1080/23744235.2021.1924397. Yong SJ Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments Infect Dis (Lond) 2021 53 10 737 754 10.1080/23744235.2021.1924397 5. Malik P, Patel K, Pinto C, Jaiswal R, Tirupathi R, Pillai S, Patel U. Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis. J Med Virol. 2022 Jan;94(1):253-62. doi: 10.1002/jmv.27309. Malik P Patel K Pinto C Jaiswal R Tirupathi R Pillai S Patel U Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis J Med Virol 2022 01 94 1 253 262 10.1002/jmv.27309 6. Mahmud R, Rahman MM, Rassel MA, Monayem FB, Sayeed SKJB, Islam MS, Islam MM. Post-COVID-19 syndrome among symptomatic COVID-19 patients: A prospective cohort study in a tertiary care center of Bangladesh. PLoS One. 2021 Apr 8;16(4):e0249644. doi: 10.1371/journal.pone.0249644. Mahmud R Rahman MM Rassel MA Monayem FB Sayeed SKJB Islam MS Islam MM Post-COVID-19 syndrome among symptomatic COVID-19 patients: A prospective cohort study in a tertiary care center of Bangladesh PLoS One 2021 04 8 16 4 e0249644 10.1371/journal.pone.0249644 7. Nascimento JHP, Gomes BFO, Carmo Júnior PRD, Petriz JLF, Rizk SI, Costa IBSDS, Lacerda MVG, et al. COVID-19 and Hypercoagulable State: A New Therapeutic Perspective. Arq Bras Cardiol. 2020 Jun 1;114(5):829-33. doi: 10.36660/abc.20200308. Nascimento JHP Gomes BFO Carmo PRD Júnior Petriz JLF Rizk SI Costa IBSDS Lacerda MVG et al COVID-19 and Hypercoagulable State: A New Therapeutic Perspective Arq Bras Cardiol 2020 06 1 114 5 829 833 10.36660/abc.20200308 8. Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, et al. TLC Study Group. Symptoms, complications and management of long COVID: a review. J R Soc Med. 2021 Sep;114(9):428-42. doi: 10.1177/01410768211032850. Aiyegbusi OL Hughes SE Turner G Rivera SC McMullan C Chandan JS et al TLC Study Group Symptoms, complications and management of long COVID: a review J R Soc Med 2021 09 114 9 428 442 10.1177/01410768211032850

Minieditorial referente ao artigo: Sintomas Cardiopulmonares Pós-COVID-19: Preditores e Características de Imagem de Pacientes após a Alta Hospitalar

Short Editorial The Clinical Impact of Cardiovascular Symptoms on Post-Acute COVID-19 Syndrome 0000-0001-7668-4224 Dutra Giovanni Possamai 1 0000-0001-7443-7270 Gomes Bruno Ferraz de Oliveira 1 2 Brasil Hospital Barra D’Or, Rio de Janeiro, RJ – Brasil Brasil Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ – Brasil Mailing Address: Bruno Ferraz de Oliveira Gomes • Rede D’Or Sao Luiz – Cardiologia – Av. Ayrton Senna, 3079. Postal code 22775-002, Rio de Janeiro, RJ – Brasil E-mail: drbrunoferraz@gmail.com COVID-19 Pandemics, Mortality Comorbidity Cardiovascular Diseases Public Health Pulmonary Heart Disease

The COVID-19 pandemic has intensely impacted people’s lives worldwide, generating, in addition to high mortality, high late morbidity, and negatively affecting health systems, remaining a significant global challenge today. In February 2023, World Health Organization records point to more than 756 million confirmed cases and approximately 6,845,000 deaths. Until the abovementioned month, approximately 36,961,000 cases were reported in Brazil, with about 698,000 deaths. Considering the substantial challenges related to comorbidity between heart disease and COVID-19, which go beyond the acute phase of the disease, further studies are needed to address the high burden of cardiopulmonary symptoms comprehensively. These investigations must be carefully planned, considering cost-effectiveness and clinical benefits for patients, to minimize inequalities in health care. In addition, it is essential to optimize social and mental care for patients. Cardiopulmonary involvement in COVID-19 continues to pose a major public health challenge.1 , 2

The study by Kalil-Filho et al.3 included 480 survivors after hospitalization due to COVID-19 and evaluated the characteristics associated with the occurrence of cardiopulmonary symptoms and, especially, post-acute COVID-19 syndrome (PACS).3 It was a sample with a predominance of men, obese and with comorbidities such as hypertension, diabetes, and dyslipidemia. Almost a quarter of patients required intensive care admission, and only 12.2% required mechanical ventilation support. The prevalence of any of the symptoms was lower (32.1%) than that found in the literature, as well as PACS related to cardiopulmonary symptoms (16.3%). Notably, almost two-thirds of the population that underwent tomography (n=122) did not demonstrate pulmonary involvement. Thus, we observed that the analyzed population had a lower degree of severity related to COVID-19, justifying the lower prevalence of symptoms.

The post-COVID syndrome that affects some patients after an acute COVID-19 event has several definitions. This syndrome is generally considered in patients who remain with symptoms after 1 to 3 months.4 The most common symptoms, reported in several studies, are fatigue, dyspnea, and sleep disturbances.5 In Kalil-Filho’s study,3 the most prevalent symptom was tiredness, which was present in almost half of the population. Symptoms such as dyspnea and cough were less prevalent and may be associated with the lower severity of these patients.

The variables most associated with cardiopulmonary symptoms were the length of hospital stay, need for intensive care unit (ICU) and mechanical ventilation, presence of critical illness polyneuropathy, and C-reactive protein (CRP) levels. Mahmud et al. found similar results.6 In this study, the variables associated with the post-COVID syndrome were female gender, duration of illness, test positivity after 14 days, and severe COVID-19. In patients with greater severity, greater activation of the inflammatory cascade and induction of the thrombotic system is expected,7 thus justifying the greater risk of maintaining symptoms in the long term.

The impact of cardiopulmonary symptoms was also evaluated in this study. Symptomatic patients had worse quality of life and a higher prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD). Aiyegbusi et al.8 showed that almost 70% of patients had some degree of physical limitation after 6 months of hospitalization. Likewise, it showed that a quarter of patients had moderate to severe symptoms of PTSD. This diagnosis was more common in women and patients with a history of psychiatric illness.8 Anxiety and depression were frequent in this study, demonstrating the relevance of Kalil-Filho’s study.3

Finally, in the multivariate analysis, we observed that the independent variables related to the diagnosis of PACS were female gender, deep vein thrombosis, troponin and C-reactive protein levels, and depression. These findings support the importance of the magnitude of the inflammatory and thrombotic response of COVID-19 in the emergence of symptoms in the long term.

The COVID-19 pandemic has had a significant impact on global public health, with high mortality and late morbidity, including the occurrence of cardiopulmonary symptoms. This study, therefore, leads to reflection on the need for comprehensive investigations to address its high frequency, considering the cost-effectiveness and clinical benefits for patients to minimize inequalities in health care. Post-COVID cardiopulmonary symptoms are multifactorial and require a multidisciplinary approach.

Short Editorial related to the article: Post-COVID-19 Cardiopulmonary Symptoms: Predictors and Imaging Features in Patients after Hospital Discharge