Synchronous and asynchronous tele-exercise during the coronavirus disease 2019 pandemic: Comparisons of implementation and training load in individuals with spinal cord injury.

INTRODUCTION: Tele-exercise could represent an alternative for remote care in individuals with spinal cord injury at this time of the pandemic of coronavirus disease 2019. However, the differences regarding the training loads and implementation between synchronous and asynchronous types are not yet known. The purpose of this study was to compare the implementation and training load between synchronous and asynchronous tele-exercise programs in individuals with spinal cord injury. METHODS: Forty individuals with spinal cord injury were recruited and stratified into tetraplegia and paraplegia groups. All subjects performed 3 weeks of both the synchronous and asynchronous tele-exercise programs, after two weeks of familiarization with the exercises, remote connection tools and methods to record information. The primary outcomes were training load (average daily workload and average and total weekly training load) and implementation (adherence and successful exercise recording). Demographic characteristics were obtained from participants' electronic medical records. RESULTS: Weekly mean workload, total workload, adherence and successful exercise recording presented significantly higher values in the synchronous compared to asynchronous tele-exercises. Average daily workload did not present significant differences between the tele-exercises. DISCUSSION: The training load for each training session presented no differences between synchronous and asynchronous tele-exercises. Both adherence and successful data recording showed more favourable implementation values for synchronous training, thus allowing greater weekly training loads (total and average).

SARS-CoV-2-Induced Amyloidgenesis: Not One, but Three Hypotheses for Cerebral COVID-19 Outcomes.

The main neuropathological feature of Alzheimer's disease (AD) is extracellular amyloid deposition in senile plaques, resulting from an imbalance between the production and clearance of amyloid beta peptides. Amyloid deposition is also found around cerebral blood vessels, termed cerebral amyloid angiopathy (CAA), in 90% of AD cases. Although the relationship between these two amyloid disorders is obvious, this does not make CAA a characteristic of AD, as 40% of the non-demented population presents this derangement. AD is predominantly sporadic; therefore, many factors contribute to its genesis. Herein, the starting point for discussion is the COVID-19 pandemic that we are experiencing and how SARS-CoV-2 may be able to, both directly and indirectly, contribute to CAA, with consequences for the outcome and extent of the disease. We highlight the role of astrocytes and endothelial cells in the process of amyloidgenesis, as well as the role of other amyloidgenic proteins, such as fibrinogen and serum amyloid A protein, in addition to the neuronal amyloid precursor protein. We discuss three independent hypotheses that complement each other to explain the cerebrovascular amyloidgenesis that may underlie long-term COVID-19 and new cases of dementia.

Clinical Features Related to Severity and Mortality among COVID-19 Patients in a Pre-Vaccine Period in Luanda, Angola.

BACKGROUND: Infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with clinical features of diverse severity. Few studies investigated the severity and mortality predictors of coronavirus disease 2019 (COVID-19) in Africa. Herein, we investigated the clinical features of severity and mortality among COVID-19 patients in Luanda, Angola. METHODS: This multicenter cohort study involved 101 COVID-19 patients, between December 2020 and April 2021, with clinical and laboratory data collected. Analysis was done using independent-sample t-tests and Chi-square tests. The results were deemed significant when p < 0.05. RESULTS: The mean age of patients was 51 years (ranging from 18 to 80 years) and 60.4% were male. Fever (46%), cough (47%), gastrointestinal symptoms (26.7%), and asthenia (26.7%), were the most common symptoms. About 64.4% of the patients presented coexistent disorders, including hypertension (42%), diabetes (17%), and chronic renal diseases (6%). About 23% were non-severe, 77% were severe, and 10% died during hospitalization. Variations in the concentration of neutrophil, urea, creatinine, c-reactive protein, sodium, creatine kinase, and chloride were independently associated with severity and/or mortality (p < 0.05). CONCLUSION: Several factors contributed to the severity and mortality among COVID-19 patients in Angola. Further studies related to clinical features should be carried out to help clinical decision-making and follow-up of COVID-19 patients in Angola.

Impact of SARS-CoV-2 infection during pregnancy on postnatal brain development: The potential role of glial cells

Glial cells are crucial for maintaining central nervous system (CNS) homeostasis. They actively participate in immune responses, as well as form functional barriers, such as blood-brain barrier (BBB), which restrict the entry of pathogens and inflammatory mediators into the CNS. In general, viral infections during the gestational period can alter the embryonic and fetal environment, and the related inflammatory response may affect neurodevelopment and lead to behavioral dysfunction during later stage of life, as highlighted by our group for Zika virus infection. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces a cytokine storm and, during pregnancy, may be related to a more severe form of the coronavirus disease-19 (COVID-19) and also to higher preterm birth rates. SARS-CoV-2 can also affect the CNS by inducing neurochemical remodeling in neural cells, which can compromise neuronal plasticity and synaptic function. However, the impact of SARS-CoV-2 infection during pregnancy on postnatal CNS, including brain development during childhood and adulthood, remains undetermined. Our group has recently highlighted the impact of COVID-19 on the expression of molecular markers associated with neuropsychiatric disorders, which are strongly related to the inflammatory response. Thus, based on these relationships, we discussed the impact of SARS-CoV-2 infection either during pregnancy or in critical periods of neurodevelopment as a risk factor for neurological consequences in the offspring later in life, focusing on the potential role of glial cells. Thus, it is important to consider future and long-term public health concerns associated with SARS-CoV-2 infection during pregnancy. [ FROM AUTHOR] Copyright of Biocell is the property of Tech Science Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Why antidiabetic drugs are potentially neuroprotective during the Sars-CoV-2 pandemic: The focus on astroglial UPR and calcium-binding proteins.

We are living in a terrifying pandemic caused by Sars-CoV-2, in which patients with diabetes mellitus have, from the beginning, been identified as having a high risk of hospitalization and mortality. This viral disease is not limited to the respiratory system, but also affects, among other organs, the central nervous system. Furthermore, we already know that individuals with diabetes mellitus exhibit signs of astrocyte dysfunction and are more likely to develop cognitive deficits and even dementia. It is now being realized that COVID-19 incurs long-term effects and that those infected can develop several neurological and psychiatric manifestations. As this virus seriously compromises cell metabolism by triggering several mechanisms leading to the unfolded protein response (UPR), which involves endoplasmic reticulum Ca2+ depletion, we review here the basis involved in this response that are intimately associated with the development of neurodegenerative diseases. The discussion aims to highlight two aspects-the role of calcium-binding proteins and the role of astrocytes, glial cells that integrate energy metabolism with neurotransmission and with neuroinflammation. Among the proteins discussed are calpain, calcineurin, and sorcin. These proteins are emphasized as markers of the UPR and are potential therapeutic targets. Finally, we discuss the role of drugs widely prescribed to patients with diabetes mellitus, such as statins, metformin, and calcium channel blockers. The review assesses potential neuroprotection mechanisms, focusing on the UPR and the restoration of reticular Ca2+ homeostasis, based on both clinical and experimental data.

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up.

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign. Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes. Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3-4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2. Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10-05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10-16). Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.

Individual variation in susceptibility or exposure to SARS-CoV-2 lowers the herd immunity threshold.

Individual variation in susceptibility and exposure is subject to selection by natural infection, accelerating the acquisition of immunity, and reducing herd immunity thresholds and epidemic final sizes. This is a manifestation of a wider population phenomenon known as "frailty variation". Despite theoretical understanding, public health policies continue to be guided by mathematical models that leave out considerable variation and as a result inflate projected disease burdens and overestimate the impact of interventions. Here we focus on trajectories of the coronavirus disease (COVID-19) pandemic in England and Scotland until November 2021. We fit models to series of daily deaths and infer relevant epidemiological parameters, including coefficients of variation and effects of non-pharmaceutical interventions which we find in agreement with independent empirical estimates based on contact surveys. Our estimates are robust to whether the analysed data series encompass one or two pandemic waves and enable projections compatible with subsequent dynamics. We conclude that vaccination programmes may have contributed modestly to the acquisition of herd immunity in populations with high levels of pre-existing naturally acquired immunity, while being crucial to protect vulnerable individuals from severe outcomes as the virus becomes endemic.

Population homogeneity for the antibody response to COVID-19 BNT162b2/Comirnaty vaccine is only reached after the second dose across all adult age ranges.

While mRNA vaccines are administrated worldwide in an effort to contain the COVID-19 pandemic, the heterogeneity of the humoral immune response they induce at the population scale remains unclear. Here, in a prospective, longitudinal, cohort-study, including 1245 hospital care workers and 146 nursing home residents scheduled for BNT162b2 vaccination, together covering adult ages from 19 to 99 years, we analyse seroconversion to SARS-CoV-2 spike protein and amount of spike-specific IgG, IgM and IgA before vaccination, and 3-5 weeks after each dose. We show that immunogenicity after a single vaccine dose is biased to IgG, heterogeneous and reduced with increasing age. The second vaccine dose normalizes IgG seroconversion in all age strata. These findings indicate two dose mRNA vaccines is required to reach population scale humoral immunity. The results advocate for the interval between the two doses not to be extended, and for serological monitoring of elderly and immunosuppressed vaccinees.

Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies.

Understanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, imposing the need to monitor SARS-CoV2 evolution and dynamics in the population. Determining signatures in SARS-CoV-2 that render the virus resistant to neutralizing antibodies is critical. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations in the spike protein, including all defining mutations in the variants of concern, to identify the effect of single and synergic amino acid substitutions in promoting immune escape. We confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations. In silico analysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and with mutations able to increase binding to ACE2, such as N501Y. Our analysis of synergic mutations provides a signature for hotspots for immune evasion and for targets of therapies, vaccines and diagnostics.

Impact of SARS-CoV-2 on neuropsychiatric disorders.

Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019 (COVID-19) from early disease onset. The most frequent symptoms and signs are fatigue, dizziness, impaired consciousness, ageusia, anosmia, radicular pain, and headache, as well as others. Based on the high number of series of cases reported, there is evidence for the implication of the immune system in the pathological mechanism of COVID-19. Although the exact role of the immunological mechanism is not elucidated, two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation. In the context of neurological manifestations associated with COVID-19, neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression, anxiety, mood alterations, psychosis, post-traumatic stress disorder, delirium, and cognitive impairment, which appear to be common in COVID-19 survivors. A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities. We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.

Production of high-quality SARS-CoV-2 antigens: Impact of bioprocess and storage on glycosylation, biophysical attributes, and ELISA serologic tests performance.

Serological assays are valuable tools to study SARS-CoV-2 spread and, importantly, to identify individuals that were already infected and would be potentially immune to a virus reinfection. SARS-CoV-2 Spike protein and its receptor binding domain (RBD) are the antigens with higher potential to develop SARS-CoV-2 serological assays. Moreover, structural studies of these antigens are key to understand the molecular basis for Spike interaction with angiotensin converting enzyme 2 receptor, hopefully enabling the development of COVID-19 therapeutics. Thus, it is urgent that significant amounts of this protein became available at the highest quality. In this study, we produced Spike and RBD in two human derived cell hosts: HEK293-E6 and Expi293F™. We evaluated the impact of different and scalable bioprocessing approaches on Spike and RBD production yields and, more importantly, on these antigens' quality attributes. Using negative and positive sera collected from human donors, we show an excellent performance of the produced antigens, assessed in serologic enzyme-linked immunosorbent assay (ELISA) tests, as denoted by the high specificity and sensitivity of the test. We show robust Spike productions with final yields of approx. 2 mg/L of culture that were maintained independently of the production scale or cell culture strategy. To the best of our knowledge, the final yield of 90 mg/L of culture obtained for RBD production, was the highest reported to date. An in-depth characterization of SARS-CoV-2 Spike and RBD proteins was performed, namely the antigen's oligomeric state, glycosylation profiles, and thermal stability during storage. The correlation of these quality attributes with ELISA performance show equivalent reactivity to SARS-CoV-2 positive serum, for all Spike and RBD produced, and for all storage conditions tested. Overall, we provide straightforward protocols to produce high-quality SARS-CoV-2 Spike and RBD antigens, that can be easily adapted to both academic and industrial settings; and integrate, for the first time, studies on the impact of bioprocess with an in-depth characterization of these proteins, correlating antigen's glycosylation and biophysical attributes to performance of COVID-19 serologic tests.