Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice (preprint)

The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x103 to 3x105 PFU/30 L) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x104 PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and were prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.

A suitable model to investigate acute neurological consequences of coronavirus infection (preprint)

Objective and design:  The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model.  Material:  Wild type C57 BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3).  Methods:  Mice were submitted to behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, synaptosome, ELISA, histopathological and immunohistochemical analysis.  Results: Increased viral titers associated with mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain, which is suggestive of excitotoxicity. Finally, behavioral analysis showed impaired motor, anhedonic and anxiety-like behaviors in animals infected with MHV-3. Conclusions: Overall, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.

Developmental Impairment in Children Exposed to Sars-Cov-2 in Utero: A Brazilian Cohort Study. (preprint)

Background The effects of in-utero exposure to maternal SARS-CoV-2 infection on the offspring's neurodevelopment are still unknown.Methods We performed a prospective cohort of babies exposed to SARS-Cov-2 during pregnancy, and a control group of unexposed babies in a low-income area in Northeastern Brazil. All data were prospectively collected from medical records. Children’s neurodevelopment was assessed using the guide for Monitoring Child Development in the IMCI context and the Ages & Stages Questionnaire (ASQ-3), at ages 4, 6, and 12 months. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS).Results We followed 127 children for one year, 69 children in the COVID-19 exposed Group (EG), and 68 in the control group (CG). All mothers were unvaccinated at the time included in the cohort. Maternal demographics were similar in the two groups, but prematurity was more prevalent in mothers infected with COVID-19 (21.7% vs. 8.8%, p = .036) and EPDS scores were also significantly higher among the EG (M = 11.00, SD = 6.00 vs. M = 8.68, SD = 4.72, p = 0.04). Both groups had similar rates of cesarean delivery, Apgar scores, average birth weight, head circumference and length at birth. 20.3% of EG children and 5.9% of the CG received a diagnosis of neurodevelopmental delay within 12 months of life (p = 0.013, RR = 3.44; 95% CI, 1.19–9.95). 10% of EG children presented abnormalities at the cranial ultrasound.Conclusions COVID-19 exposure was associated with neurodevelopmental impairment. This study highlights the importance of specific guidelines in the follow-up of children exposed to in-utero SARS-CoV-2 in order to mitigate or prevent long-term effects on children’s health.

Human endogenous retrovirus K activation in the lower respiratory tract of severe COVID-19 patients associates with early mortality (preprint)

Critically ill 2019 coronavirus disease patients (COVID-19) under invasive mechanical ventilation (IMV) are 10- to 40-times more likely to die than the general population. Although progression from mild to severe COVID-19 has been associated with hypoxia, uncontrolled inflammation and coagulopathy, the mechanisms involved in progression to severity are poorly understood. By analyzing the virome from tracheal aspirates (TA) of 25 COVID-19 patients under IMV, we found higher levels and differential expression of human endogenous retrovirus K (HERV-K) genes compared to nasopharyngeal swabs from mild cases and TA from non-COVID patients. Proteomic analysis and RT-PCR confirmed the presence of HERV-K in these patients. Moreover, increased HERV-K expression was triggered in human primary monocytes from healthy donors after experimental SARS-CoV-2 infection in vitro. In critically ill patients, higher HERV-K levels were associated with early mortality (within 14 days) in the intensive care unit. Increased HERV-K expression in deceased patients associated with IL-17-related inflammation, monocyte activation and higher consumption of clotting/fibrinolysis factors. Our data implicate the levels of HERV-K transcripts in the outcome of critical COVID-19 patients under invasive mechanical ventilation.

Renin-Angiotensin System in Central Nervous System Diseases and its Interaction with COVID-19.

BACKGROUND: The Renin-Angiotensin System (RAS) comprises a complex molecular cascade with two counter-regulatory axes, the classical and the alternative. Angiotensin II and Angiotensin-(1-7), the main peptides of the RAS, exert opposite effects in multiple organs and systems, including the cardiovascular, renal, pulmonary, and immune systems. Strong evidence supports the hypothesis of a local RAS in the Central Nervous System (CNS) and its modulatory roles in neuroendocrinology and neurotransmission. OBJECTIVE: In this narrative review, we provide a comprehensive approach to experimental and clinical data regarding RAS molecule expression and their possible roles in the physiology and physiopathology of CNS diseases. METHODS: This non-systematic review summarizes evidence on RAS implications in CNS diseases and their possible relationships with COVID-19. RESULTS: We divided the possible RAS mechanisms in distinct conditions during the lifespan, approaching from congenital infections to neurodegenerative alterations, passing through mood disorders and cerebrovascular diseases. We also gathered current evidence about the possible effects of RAS in Covid-19, particularly in cases with neurological manifestations. CONCLUSION: Although there are limitations and controversies, the analysis of RAS mechanisms in the CNS certainly represents an interesting field of research. However, further investigation is necessary to support the noteworthy interactions and provide a better comprehension of the cross-talk between RAS and the CNS. Investigations in this research field may shed light on the novel therapeutic targets.

Musical strategy to care for nursing students: experience in coping with covid-19

Objetivo relatar a experiência do uso de estratégia musical para cuidar de discentes de Enfermagem no enfrentamento da Coronavirus disease 2019 (COVID-19). Método trata-se de relato de experiência da construção de um vídeo musical, envolvendo 32 enfermeiros, docentes do curso de graduação em Enfermagem de uma Universidade pública do Sul do Brasil. Resultados o vídeo musical foi estruturado para que pudesse refletir a relevância dos discentes no cotidiano da Universidade. A música balizou os sentimentos que são necessários externalizar nesse período de pandemia, que ocasionalmente mostrou as mudanças abruptas relativas ao vivido. Conclusão a estratégia mostrou-se promotora de saúde e articuladora entre os docentes e discentes, apontando novas perspectivas de cuidado que ultrapassam as barreiras da presencialidade, vislumbrando o uso das tecnologias em prol da ampliação dos horizontes para o cuidado, em tempos de distanciamento social e quarentena. Objetivo informar la experiencia del uso de la estrategia musical para el cuidado de los estudiantes de enfermería en el enfrentamiento de la Coronavirus disease 2019 (COVID-19). Método este es un informe de experiencia de la construcción de un video musical, en el que participan 32 enfermeras, docentes del curso de graduación en Enfermería de una Universidad Pública en el Sur de Brasil. Resultados el vídeo musical se estructuró para que pudiera reflejar la relevancia de los estudiantes en la vida cotidiana de la Universidad. La música sacudió los sentimientos que se necesitan externalización en este período de pandemia, que ocasionalmente mostró los cambios abruptos relacionados con el vivido. Conclusión la estrategia resultó ser promotora y articuladora de la salud entre docentes y estudiantes, señalando nuevas perspectivas de atención que superan las barreras del presencial, vislumbrando el uso de tecnologías en favor de ampliar los horizontes para el cuidado, en tiempos de distanciamiento social y cuarentena.

Musical strategy to care for nursing students: experience in coping with covid-19

Objetivo relatar a experiência do uso de estratégia musical para cuidar de discentes de Enfermagem no enfrentamento da Coronavirus disease 2019 (COVID-19). Método trata-se de relato de experiência da construção de um vídeo musical, envolvendo 32 enfermeiros, docentes do curso de graduação em Enfermagem de uma Universidade pública do Sul do Brasil. Resultados o vídeo musical foi estruturado para que pudesse refletir a relevância dos discentes no cotidiano da Universidade. A música balizou os sentimentos que são necessários externalizar nesse período de pandemia, que ocasionalmente mostrou as mudanças abruptas relativas ao vivido. Conclusão a estratégia mostrou-se promotora de saúde e articuladora entre os docentes e discentes, apontando novas perspectivas de cuidado que ultrapassam as barreiras da presencialidade, vislumbrando o uso das tecnologias em prol da ampliação dos horizontes para o cuidado, em tempos de distanciamento social e quarentena. Objetivo informar la experiencia del uso de la estrategia musical para el cuidado de los estudiantes de enfermería en el enfrentamiento de la Coronavirus disease 2019 (COVID-19). Método este es un informe de experiencia de la construcción de un video musical, en el que participan 32 enfermeras, docentes del curso de graduación en Enfermería de una Universidad Pública en el Sur de Brasil. Resultados el vídeo musical se estructuró para que pudiera reflejar la relevancia de los estudiantes en la vida cotidiana de la Universidad. La música sacudió los sentimientos que se necesitan externalización en este período de pandemia, que ocasionalmente mostró los cambios abruptos relacionados con el vivido. Conclusión la estrategia resultó ser promotora y articuladora de la salud entre docentes y estudiantes, señalando nuevas perspectivas de atención que superan las barreras del presencial, vislumbrando el uso de tecnologías en favor de ampliar los horizontes para el cuidado, en tiempos de distanciamiento social y cuarentena.

Coronavirus Disease-2019 Conundrum: RAS Blockade and Geriatric-Associated Neuropsychiatric Disorders.

Coronavirus Disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily targets the human respiratory system and may lead to severe pneumonia and ultimately death. Mortality rate is particurlarly high among people beyond the sixth decade of life with cardiovascular and metabolic diseases. The discovery that the SARS-CoV-2 uses the renin-angiotensin system (RAS) component ACE2 as a receptor to invade host epithelial cells and cause organs damage resulted in a debate regarding the role of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) therapies during COVID-19 pandemic. Some authors proposed the discontinuation of ACEIs and ARBs for cardiovascular, kidney, and metabolic diseases, while expert opinions have discouraged that due to limited empirical evidence of their negative effect on COVID-19 outcomes, and that withdrawing treatment may contribute to clinical decompensation in high-risk patients. Moreover, as cardiovascular and metabolic diseases are associated with neurodegenerative and psychiatric disorders, especially among older adults, a critical appraisal of the potential positive effects of ACEIs and ARBs is highly needed. Herein, we aim to discuss the conundrum of ACEIs and ARBs use in high-risk patients for COVID-19, and their potential protective role on the development and/or progression of geriatric neuropsychiatric disorders.

Caring for elderly people during the COVID-19 pandemic: the experience of family caregivers.

OBJECTIVE: To build a theoretical model that represents the experience of family caregivers of elderly people during the COVID-19 pandemic. METHOD: Qualitative study that used the Grounded Theory as a methodology, carried out in Minas Gerais State in August 2020. 16 caregivers were interviewed. RESULTS: Uncomfortable emotions emerged and drove the caregivers' actions to: adopt preventive measures to protect the elderly from contracting the coronavirus; guarantee their healthcare; and make them aware of the pandemic. However, when these emotions manifested in an exacerbated manner, they needed to be alleviated so that they could adopt such initiatives. CONCLUSION: The emotions felt by caregivers can compromise their health and quality of life. Therefore, health professionals need to create strategies to ensure that they are well assisted, enabling care through telehealth. Guidance on the pandemic for caregivers could reflect better care for the elderly people.