A high CMV-specific T cell response associates with SARS-CoV-2-specific IL-17 T cell production.

Human cytomegalovirus (CMV) is a widespread persistent herpes virus requiring lifelong immune surveillance to maintain latency. Such long-term interactions with the immune system may be associated with deleterious effects including immune exhaustion and senescence. Regarding the COVID-19 pandemic, we asked whether CMV-specific cellular and humoral activity could influence immune responses toward SARS-CoV-2 and/or disease severity. All adults with mild (n = 15) and severe (n = 14) COVID-19 were seropositive for anti-CMV IgG, but negative for IgM antibodies. Antibody titers did not correlate with COVID-19 severity. Six patients presented elevated frequencies of CMV-specific CD4 + and CD8 + T cells producing IFNγ, IL-17, and TNFα, designated as CMV high responders (hiT CMV). In comparison to low CMV responders, hiT CMV individuals exhibited higher frequencies of SARS-CoV-2-specific CD4 + IL-17 + and CD8 + IFNγ + , IL-17 + or TNFα + T cells. These results indicate that high frequencies of CMV-specific T cells may be associated with a SARS-CoV-2-reactive profile skewed toward Th17-dominated immunity.

Rhinovirus as the main co-circulating virus during the COVID-19 pandemic in children

Abstract Objective: Changes in the epidemiology of respiratory infections during the restrictions imposed as a response to the coronavirus disease 2019 (COVID-19) pandemic have been reported elsewhere. The present study's aim was to describe the prevalence of a large array of respiratory pathogens in symptomatic children and adolescents during the pandemic in Southern Brazil. Methods: Hospitalized and outpatients aged 2 months to 18 years with signs and symptoms of acute COVID-19 were prospectively enrolled in the study from May to November 2020 in two hospitals in a large metropolitan area in a Brazilian city. All participants performed a real-time PCR panel assessing 20 respiratory pathogens (three bacteria and 17 viruses). Results: 436 participants were included, with 45 of these hospitalized. Rhinovirus was the most prevalent pathogen (216/436) followed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 97/436), with a coinfection of these two viruses occurring in 31/436 participants. The remaining pathogens were found in 24 symptomatic participants (adenovirus, n = 6; Chlamydophila pneumoniae, n = 1; coronavirus NL63, n = 2; human enterovirus, n = 7; human metapneu-movirus, n = 2; Mycoplasma pneumoniae, n = 6). Hospitalization was more common among infants (p = 0.004) and those with pathogens other than SARS-CoV-2 (p = 0.001). Conclusion: During the period of social distancing in response to COVID-19, the prevalence of most respiratory pathogens was unusually low. Rhinovirus remained as the main virus co-circulating with SARS-CoV-2. COVID-19 in symptomatic children was less associated with hospitalization than with other respiratory infections in children and adolescents.

SARS-CoV-2 infected children form early immune memory responses dominated by nucleocapsid-specific CD8+ T cells and antibodies.

This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children's anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8+T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected.

Association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil: a prospective cohort study.

Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.

Association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil: a prospective cohort study

ABSTRACT Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects and methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.

Impact of rhinovirus on hospitalization during the COVID-19 pandemic: A prospective cohort study.

BACKGROUND: Although the clinical course of the COVID-19 in adults has been extensively described, the impact of the co-detection of SARS-CoV-2 and rhinovirus on severity outcomes is not understood. OBJECTIVES: This study aimed to compare the risk of hospitalization of outpatients with COVID-19 with and without the co-detection of rhinovirus in southern Brazil. Secondarily, such risk was also compared between all individuals with COVID-19 and those with single rhinovirus infection. STUDY DESIGN: Outpatients (>18 years) with acute signs of cough, fever, or sore throat were prospectively enrolled at two emergency departments from May to September 2020. Sample collection was performed to detect SARS-CoV-2 and other 20 respiratory pathogens. Participants were followed for 28 days through telephone interviews. RESULTS: 1,047 participants were screened and 1,044 were included. Of these, 4.9% were lost during follow-up, and 993/1,044 (95.1%) were included in severity-related analysis. Rhinovirus was the most prevalent pathogen (25.0%, 248/993), followed by SARS-CoV-2 (22.6%, 224/993), with coinfection of these two viruses occurring in 91/993 (9.2%) participants. The risk of COVID-19-related hospitalizations were not different between individuals with and without co-detection of rhinovirus (9.9% vs. 7.6%, respectively, P = 0.655). Conversely, subjects with COVID-19 had a higher hospitalization risk than single rhinovirus infection (8.3 vs 0.4%, respectively, P < 0.001). CONCLUSIONS: The co-detection of SARS-CoV-2 and rhinovirus did not change the risk of hospitalizations in adults. Furthermore, COVID-19 was more severe than single rhinovirus infection.

Rhinovirus as the main co-circulating virus during the COVID-19 pandemic in children.

OBJECTIVE: Changes in the epidemiology of respiratory infections during the restrictions imposed as a response to the coronavirus disease 2019 (COVID-19) pandemic have been reported elsewhere. The present study's aim was to describe the prevalence of a large array of respiratory pathogens in symptomatic children and adolescents during the pandemic in Southern Brazil. METHODS: Hospitalized and outpatients aged 2 months to 18 years with signs and symptoms of acute COVID-19 were prospectively enrolled in the study from May to November 2020 in two hospitals in a large metropolitan area in a Brazilian city. All participants performed a real-time PCR panel assessing 20 respiratory pathogens (three bacteria and 17 viruses). RESULTS: 436 participants were included, with 45 of these hospitalized. Rhinovirus was the most prevalent pathogen (216/436) followed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 97/436), with a coinfection of these two viruses occurring in 31/436 participants. The remaining pathogens were found in 24 symptomatic participants (adenovirus, n = 6; Chlamydophila pneumoniae, n = 1; coronavirus NL63, n = 2; human enterovirus, n = 7; human metapneumovirus, n = 2; Mycoplasma pneumoniae, n = 6). Hospitalization was more common among infants (p = 0.004) and those with pathogens other than SARS-CoV-2 (p = 0.001). CONCLUSION: During the period of social distancing in response to COVID-19, the prevalence of most respiratory pathogens was unusually low. Rhinovirus remained as the main virus co-circulating with SARS-CoV-2. COVID-19 in symptomatic children was less associated with hospitalization than with other respiratory infections in children and adolescents.

Low performance of a SARS-CoV-2 point-of-care lateral flow immunoassay in symptomatic children during the pandemic

Abstract Objective: to evaluate the accuracy of an antibody point-of-care lateral flow immunoassay (LFI -Wondfo Biotech Co., Guangzhou, China) in a pediatric population. Methods: children and adolescents (2 months to 18 years) with signs and symptoms suggestive of acute SARS-CoV-2 infection were prospectively investigated with nasopharyngeal RT-PCR and LFI at the emergency room. RT-PCR was performed at baseline, and LFI at the same time or scheduled for those with less than 7 days of the clinical picture. Overall accuracy, sensitivity and specificity were assessed, as well as according to the onset of symptoms (7-13 or ≥14 days) at the time of the LFI test. Results: In 175 children included, RT-PCR and LFI were positive in 51 (29.14%) and 36 (20.57%), respectively. The overall sensitivity, specificity, positive and negative predictive value was 70.6% (95%CI 56.2-82.5), 96.8% (95%CI 91.9-99.1), 90.0% (95%CI 77.2-96.0), and 88.9% (95%CI 83.9-92.5), respectively. At 7-13 and ≥14 days after the onset of symptoms, sensitivity was 60.0% (95%CI 26.2-87.8) and 73.2% (95%CI 57.1-85.8) and specificity was 97.9% (95%CI 88.7-99.9) and 96.1% (95%CI 89.0-99.2), respectively. Conclusion: Despite its high specificity, in the present study the sensitivity of LFI in children was lower (around 70%) than most reports in adults. Although a positive result is informative, a negative LFI test cannot rule out COVID-19 in children.

Diagnostic yield of multi-gene panel for muscular dystrophies and other hereditary myopathies.

Genetic testing is being considered the first-step in the investigation of hereditary myopathies. However, the performance of the different testing approaches is little known. The aims of the present study were to evaluate the diagnostic yield of a next-generation sequencing panel comprising 39 genes as the first-tier test for genetic myopathies diagnosis and to characterize clinical and molecular findings of families from southern Brazil. Fifty-one consecutive index cases with clinical suspicion of genetic myopathies were recruited from October 2014 to March 2018 in a cross-sectional study. The overall diagnostic yield of the next-generation sequencing panel was 52.9%, increasing to 60.8% when including cases with candidate variants. Multi-gene panel solved the diagnosis of 12/25 (48%) probands with limb-girdle muscular dystrophies, of 7/14 (50%) with congenital muscular diseases, and of 7/10 (70%) with muscular dystrophy with prominent joint contractures. The most frequent diagnosis for limb-girdle muscular dystrophies were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related; for congenital muscular diseases, RYR1-related-disorders; and for muscular dystrophy with prominent joint contractures, Emery-Dreifuss-muscular-dystrophy-type-1 and COL6A1-related-disorders. In summary, the customized next-generation sequencing panel when applied in the initial investigation of genetic myopathies results in high diagnostic yield, likely reducing patient's diagnostic odyssey and providing important information for genetic counseling and participation in disease-specific clinical trials.

Y380Q novel mutation in receptor-binding domain of SARS-CoV-2 spike protein together with C379W interfere in the neutralizing antibodies interaction.

We aimed to describe the SARS-CoV-2 lineages circulating early pandemic among samples with S gene dropout and characterize the receptor-binding domain (RBD) of viral spike protein. Adults and children older than 2 months with signs and symptoms of COVID-19 were prospectively enrolled from May to October in Porto Alegre, Brazil. All participants performed RT-PCR assay, and samples with S gene dropout and cycle threshold < 30 were submitted to high-throughput sequencing (HTS). 484 out of 1,557 participants tested positive for SARS-CoV-2. The S gene dropout was detected in 7.4% (36/484) and a peak was observed in August. The B.1.1.28, B.1.91 and B.1.1.33 lineages were circulating in early pandemic. The RBD novel mutation (Y380Q) was found in one sample occurring simultaneously with C379W and V395A, and the B.1.91 lineage in the spike protein. The Y380Q and C379W may interfere with the binding of neutralizing antibodies (CR3022, EY6A, H014, S304).

Diagnostic accuracy of a SARS-CoV-2 rapid test and optimal time for seropositivity according to the onset of symptoms.

Point-of-care serological tests for SARS-CoV-2 have been used for COVID-19 diagnosis. However, their accuracy over time regarding the onset of symptoms is not fully understood. We aimed to assess the accuracy of a point-of-care lateral flow immunoassay (LFI). Subjects, aged over 18 years, presenting clinical symptoms suggestive of acute SARS-CoV-2 infection were tested once by both nasopharyngeal and oropharyngeal RT-PCR and LFI. The accuracy of LFI was assessed in periodic intervals of three days in relation to the onset of symptoms. The optimal cut-off point was defined as the number of days required to achieve the best sensitivity and specificity. This cut-off point was also used to compare LFI accuracy according to participants' status: outpatient or hospitalized. In total, 959 patients were included, 379 (39.52%) tested positive for SARS-CoV-2 with RT-PCR, and 272 (28.36%) tested positive with LFI. LFI best performance was achieved after 10 days of the onset of symptoms, with sensitivity and specificity of 84.9% (95%CI: 79.8-89.1) and 94.4% (95%CI: 91.0-96.8), respectively. Although the specificity was similar (94.6% vs. 88.9%, p = 0.051), the sensitivity was higher in hospitalized patients than in outpatients (91.7% vs. 82.1%, p = 0.032) after 10 days of the onset of symptoms. Best sensitivity of point-of-care LFI was found 10 days after the onset of symptoms which may limit its use in acute care. Specificity remained high regardless of the number of days since the onset of symptoms.

Low performance of a SARS-CoV-2 point-of-care lateral flow immunoassay in symptomatic children during the pandemic.

OBJECTIVE: to evaluate the accuracy of an antibody point-of-care lateral flow immunoassay (LFI - Wondfo Biotech Co., Guangzhou, China) in a pediatric population. METHODS: children and adolescents (2 months to 18 years) with signs and symptoms suggestive of acute SARS-CoV-2 infection were prospectively investigated with nasopharyngeal RT-PCR and LFI at the emergency room. RT-PCR was performed at baseline, and LFI at the same time or scheduled for those with less than 7 days of the clinical picture. Overall accuracy, sensitivity and specificity were assessed, as well as according to the onset of symptoms (7-13 or ≥14 days) at the time of the LFI test. RESULTS: In 175 children included, RT-PCR and LFI were positive in 51 (29.14%) and 36 (20.57%), respectively. The overall sensitivity, specificity, positive and negative predictive value was 70.6% (95%CI 56.2-82.5), 96.8% (95%CI 91.9-99.1), 90.0% (95%CI 77.2-96.0), and 88.9% (95%CI 83.9-92.5), respectively. At 7-13 and ≥14 days after the onset of symptoms, sensitivity was 60.0% (95%CI 26.2-87.8) and 73.2% (95%CI 57.1-85.8) and specificity was 97.9% (95%CI 88.7-99.9) and 96.1% (95%CI 89.0-99.2), respectively. CONCLUSION: Despite its high specificity, in the present study the sensitivity of LFI in children was lower (around 70%) than most reports in adults. Although a positive result is informative, a negative LFI test cannot rule out COVID-19 in children.

Diagnostic accuracy of a SARS-CoV-2 rapid test and optimal time for seropositivity according to the onset of symptoms / Acurácia diagnóstica de um teste rápido para SARS-CoV-2 e tempo ótimo para a soropositividade a partir do início dos sintomas / Precisión diagnóstica del test rápido SARS-CoV-2 y período óptimo para la seropositividad según la aparición de síntomas

Point-of-care serological tests for SARS-CoV-2 have been used for COVID-19 diagnosis. However, their accuracy over time regarding the onset of symptoms is not fully understood. We aimed to assess the accuracy of a point-of-care lateral flow immunoassay (LFI). Subjects, aged over 18 years, presenting clinical symptoms suggestive of acute SARS-CoV-2 infection were tested once by both nasopharyngeal and oropharyngeal RT-PCR and LFI. The accuracy of LFI was assessed in periodic intervals of three days in relation to the onset of symptoms. The optimal cut-off point was defined as the number of days required to achieve the best sensitivity and specificity. This cut-off point was also used to compare LFI accuracy according to participants' status: outpatient or hospitalized. In total, 959 patients were included, 379 (39.52%) tested positive for SARS-CoV-2 with RT-PCR, and 272 (28.36%) tested positive with LFI. LFI best performance was achieved after 10 days of the onset of symptoms, with sensitivity and specificity of 84.9% (95%CI: 79.8-89.1) and 94.4% (95%CI: 91.0-96.8), respectively. Although the specificity was similar (94.6% vs. 88.9%, p = 0.051), the sensitivity was higher in hospitalized patients than in outpatients (91.7% vs. 82.1%, p = 0.032) after 10 days of the onset of symptoms. Best sensitivity of point-of-care LFI was found 10 days after the onset of symptoms which may limit its use in acute care. Specificity remained high regardless of the number of days since the onset of symptoms.

Os testes sorológicos no local de atendimento (point-of-care) para a infecção pelo SARS-CoV-2 têm sidos utilizados para o diagnóstico da COVID-19. Entretanto, não está plenamente elucidada a acurácia dos testes ao longo do tempo em relação ao início dos sintomas. Nosso objetivo foi de avaliar a acurácia, no local de atendimento, do imunoensaio de fluxo lateral (LFI). Pacientes com ≥ 18 anos de idade que apresentavam sintomas clínicos sugestivos de infecção aguda pelo SARS-CoV-2 foram testados uma vez com RT-PCR da nasofaringe e orofaringe, além do LFI. A acurácia do LFI foi avaliada com intervalos periódicos de 3 dias a partir do início dos sintomas. O ponto de corte ótimo foi definido como o número necessário de dias para atingir a melhor sensibilidade e especificidade. Esse ponto foi utilizado também para comparar a acurácia do LFI de acordo com a situação do paciente (ambulatorial ou hospitalizado). Foram incluídos 959 pacientes, dos quais 379 (39,52%) testaram positivos para SARS-CoV-2 pelo RT-PCR e 272 (28,36%) pelo LFI. Foi atingido o melhor desempenho para o LFI com 10 dias a partir do início dos sintomas, com sensibilidade e especificidade de 84,9% (IC95%: 79,8-89,1) e 94,4% (IC95%: 91,0-96,8), respectivamente. Embora a especificidade não tenha sido diferente entre os grupos de pacientes (94,6% vs. 88,9%, p = 0,051), a sensibilidade foi mais alta nos pacientes hospitalizados que nos ambulatoriais (91,7% vs. 82,1%, p = 0,032) no dia 10 depois do início dos sintomas. A melhor sensibilidade do LFI no local de atendimento ocorre 10 dias depois do início dos sintomas, o que pode limitar seu uso no atendimento agudo. A especificidade permanece alta, independentemente do número de dias desde o início dos sintomas.

Los puestos de atención para pruebas serológicas del SARS-CoV-2 han sido usado para la diagnosis de la COVID-19. No obstante, su precisión a lo largo del tiempo, en lo que respecta a la aparición de los síntomas, no se ha comprendido completamente. Nuestro objetivo fue evaluar la precisión de un puesto de atención de inmunoanálisis de flujo lateral (LFI). Se hizo pruebas a individuos ≥ 18 años, presentando síntomas clínicos compatibles con una infección aguda de SARS-CoV-2, tanto vía nasofaríngea y orofaríngea RT-PCR, como LFI. La precisión de LFI fue evaluada en intervalos periódicos de 3 días con respecto a la aparición de los síntomas. El punto óptimo de corte se definió como el número de días requerido para alcanzar la mejor sensibilidad y especificidad. Este punto también se usó para comparar la precisión del LFI, según el estatus de los participantes: ambulatorios u hospitalizados. Se incluyeron a 959 pacientes, 379 (39,52%) dieron positivo en las pruebas de SARS-CoV-2 RT-PCR, y 272 (28,36%) fueron positivos en los LFI. Se alcanzó el mejor rendimiento de los LFI tras 10 días de la aparición de los síntomas, con una sensibilidad y especificidad de un 84,9% (IC95%: 79,8-89,1) y 94,4% (IC95%: 91,0-96,8), respectivamente. A pesar de que la especificidad no fue diferente (94,6% vs. 88,9%, p = 0,051), la sensibilidad fue mayor en pacientes hospitalizados que en los ambulatorios (91,7% vs. 82,1%, p = 0,032) tras 10 días desde la aparición de los síntomas. La mejor sensibilidad LFI del puesto de cuidado se produce tras 10 días de la aparición de los síntomas, lo que quizás limite su uso en el cuidado de urgencias. La especificidad permanece alta independientemente del número de días desde la aparición de los síntomas.

Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses.

COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children's non-specific immune profile is dominated by naive lymphocytes and HLA-DRhighCX3CR1low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8+TNF+ T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus.

Children Have Similar Reverse Transcription Polymerase Chain Reaction Cycle Threshold for Severe Acute Respiratory Syndrome Coronavirus 2 in Comparison With Adults.

BACKGROUND: The viral dynamics and the role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not completely understood. Our aim was to evaluate reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) values among children with confirmed SARS-CoV-2 compared with that of adult subjects. METHODS: Patients (from 2 months to ≤18 years of age and adults) with signs and symptoms of acute SARS-CoV-2 infection for less than 7 days were prospectively enrolled in the study from May to November 2020. All participants performed RT-PCR assay for SARS-CoV-2 detection; Ct values of ORF1ab, N and S gene targets and the average of all the 3 probes were used as surrogates of viral load. RESULTS: There were 21 infants (2 months to <2 years), 40 children (≥2 to <12 years), 22 adolescents (≥12 to <18 years) and 293 adults of 376 participants with confirmed SARS-CoV-2 infections. RT-PCR Ct values from all participants less than 18 years of age, as well as from all childhood subgroups, were not significantly different from adults, comparing ORF1ab, N, S and all the gene targets together (P = 0.453). CONCLUSIONS: Ct values for children were comparable with that of adults. Although viral load is not the only determinant of SARS-CoV-2 transmission, children may play a role in the spread of coronavirus disease 2019 in the community.

Absence of detection of RSV and influenza during the COVID-19 pandemic in a Brazilian cohort: Likely role of lower transmission in the community.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are prevalent seasonal community viruses. Although not completely understood, SARS-CoV-2 may have the same means of transmission. Preventive social measures aimed at preventing SARS-CoV-2 spread could impact transmission of other respiratory viruses as well. The aim of this study is to report the detection of RSV and influenza during the period of social distancing due to COVID-19 pandemic in a heavily affected community. METHODS: Prospective study with pediatric and adult populations seeking care for COVID-19-like symptoms during the fall and winter of 2020 at two hospitals in Southern Brazil. RT-PCR tests for SARS-CoV-2, influenza A (Flu A), influenza B (Flu B) and respiratory syncytial virus (RSV) was performed for all participants. RESULTS: 1435 suspected COVID-19 participants (1137 adults, and 298 children). were included between May and August. Median age was 37.7 years (IQR = 29.6-47.7), and 4.92 years (IQR = 1.96-9.53), for the adult and child cohorts, respectively. SARS-CoV-2 was positive in 469 (32.7%) while influenza and RSV were not detected at all. CONCLUSIONS: Measures to reduce SARS-CoV-2 transmission likely exerted a huge impact in the spread of alternate respiratory pathogens. These findings contribute to the knowledge about the dynamics of virus spread. Further, it may be considered for guiding therapeutic choices for these other viruses.

Free carnitine and branched chain amino acids are not good biomarkers in Huntington's disease.

BACKGROUND: Huntington's disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. OBJECTIVE: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. METHODS: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured. Baseline and longitudinal analysis were performed. RESULTS: Seventy-four symptomatic carriers, 20 asymptomatic carriers, and 22 non-carriers were included. At baseline, valine levels were reduced in symptomatic and asymptomatic HD carriers when compared to non-carriers. No difference in free carnitine or isoleucine+leucine levels were observed between groups. BMI of symptomatic individuals was lower than those of non-carriers. Valine levels correlated with BMI. Follow-up evaluation was performed in 43 symptomatic individuals. UHDRS total motor score increased 4.8 points/year on average. No significant reductions in BMI or valine were observed, whereas free carnitine and isoleucine+leucine levels increased. CONCLUSIONS: Although valine levels were lower in HD carriers and were related to BMI losses observed in pre-symptomatic individuals, none of these metabolites seem to be biomarkers for HD.

Free carnitine and branched chain amino acids are not good biomarkers in Huntington's disease / Carnitina livre e aminoácidos de cadeia ramificada não são bons biomarcadores na doença de Huntington

ABSTRACT Background: Huntington's disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. Objective: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. Methods: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured. Baseline and longitudinal analysis were performed. Results: Seventy-four symptomatic carriers, 20 asymptomatic carriers, and 22 non-carriers were included. At baseline, valine levels were reduced in symptomatic and asymptomatic HD carriers when compared to non-carriers. No difference in free carnitine or isoleucine+leucine levels were observed between groups. BMI of symptomatic individuals was lower than those of non-carriers. Valine levels correlated with BMI. Follow-up evaluation was performed in 43 symptomatic individuals. UHDRS total motor score increased 4.8 points/year on average. No significant reductions in BMI or valine were observed, whereas free carnitine and isoleucine+leucine levels increased. Conclusions: Although valine levels were lower in HD carriers and were related to BMI losses observed in pre-symptomatic individuals, none of these metabolites seem to be biomarkers for HD.

RESUMO Introdução: A doença de Huntington (DH), causada por uma repetição CAG expandida no HTT, não possui tratamento e biomarcadores são necessários para futuros ensaios clínicos. Objetivo: Nosso objetivo foi verificar se os níveis de carnitina livre e aminoácidos de cadeia ramificada se comportam como potenciais biomarcadores na DH. Métodos: Portadores sintomáticos e assintomáticos e controles foram recrutados. Idade, sexo, índice de massa corporal (IMC), idade de início, duração da doença, escores UHDRS e trato CAG expandido foram obtidos; valina, leucina, isoleucina e carnitina livre foram medidas. Foram realizadas análises basal e longitudinal. Resultados: Setenta e quatro portadores sintomáticos, 20 portadores assintomáticos e 22 não portadores foram incluídos. No início do estudo, os níveis de valina estavam reduzidos em portadores de DH sintomáticos e assintomáticos quando comparados aos não portadores. Não foram observadas diferenças nos níveis de carnitina livre ou isoleucina + leucina entre os grupos. O IMC dos indivíduos sintomáticos foi menor que o dos não portadores. Níveis de valina correlacionaram-se com o IMC. Avaliação de acompanhamento foi realizada em 43 indivíduos sintomáticos. A pontuação do escore motor total da UHDRS aumentou 4,8 pontos/ano em média. Não foram observadas reduções significativas no IMC ou na valina, enquanto os níveis de carnitina livre e isoleucina+leucina aumentaram. Conclusões: Embora os níveis de valina tenham sido menores nos portadores de DH e estivessem relacionados às perdas de IMC observadas em indivíduos pré-sintomáticos, nenhum desses metabólitos parece ser biomarcador para a DH.

Prevalence of oropharyngeal dysphagia in hereditary spastic paraplegias / Prevalência de disfagia orofaríngea nas paraparesias espásticas hereditárias

ABSTRACT Hereditary spastic paraplegias (HSP) are a group of genetic diseases characterized by lower limb spasticity with or without additional neurological features. Swallowing dysfunction is poorly studied in HSP and its presence can lead to significant respiratory and nutritional complications. Objectives: The aim of this study was to evaluate the frequency and clinical characteristics of dysphagia in different types of HSP. Methods: A two-center cross-sectional prevalence study was performed. Genetically confirmed HSP patients were evaluated using the Northwestern Dysphagia Patient Check Sheet and the Functional Oral Intake Scale. In addition, self-perception of dysphagia was assessed by the Eat Assessment Tool-10 and the Swallowing Disturbance Questionnaire. Results: Thirty-six patients with spastic paraplegia type 4 (SPG4), five with SPG11, four with SPG5, four with cerebrotendinous xanthomatosis (CTX), three with SPG7, and two with SPG3A were evaluated. Mild to moderate oropharyngeal dysphagia was present in 3/5 (60%) of SPG11 and 2/4 (50%) of CTX patients. A single SPG4 (2%) and a single SPG7 (33%) patient had mild oropharyngeal dysphagia. All other evaluated patients presented with normal or functional swallowing. Conclusions: Clinically significant oropharyngeal dysphagia was only present in complicated forms of HSP Patients with SPG11 and CTX had the highest risks for dysphagia, suggesting that surveillance of swallowing function should be part of the management of patients with these disorders.

RESUMO As paraparesias espásticas hereditárias (PEH) são um grupo de doenças genéticas caracterizado por espasticidade dos membros inferiores com ou sem características neurológicas adicionais. A disfunção da deglutição é pouco estudada nas PEH e sua presença pode levar a complicações respiratórias e nutricionais significativas. Objetivo: O objetivo deste estudo foi avaliar a frequência e a caracterização clínica da disfagia em diferentes tipos de PEH. Métodos: Foi realizado um estudo transversal em dois centros. Os pacientes com PEH confirmados geneticamente foram avaliados pelo Northwestern Dysphagia Patient Check Sheet e pela Escala Funcional de Ingestão Oral. Além disso, a autopercepção da disfagia foi avaliada pelo Eat Assessment Tool-10 e pelo Swallowing Disturbance Questionnaire. Resultados: Trinta e seis pacientes com paraplegia espástica tipo 4 (SPG4), cinco com SPG11, quatro com SPG5, quatro com xantomatose cerebrotendinosa (CTX), três com SPG7 e dois com SPG3A foram avaliados. Disfagia orofaríngea leve a moderada estava presente em 3/5 (60%) dos pacientes com SPG11 e 2/4 (50%) dos pacientes com CTX. Um único SPG4 (2%) e um único SPG7 (33%) apresentaram disfagia orofaríngea leve. Todos os outros pacientes avaliados apresentaram deglutição normal ou funcional. Conclusão: Disfagia orofaríngea clinicamente significativa estava presente apenas nas formas complicadas de PEH. A SPG11 e CTX apresentaram maiores riscos de disfagia, sugerindo que a avaliação da deglutição deve fazer parte do manejo dos pacientes com essas condições.

Minimal prevalence of Huntington's disease in the South of Brazil and instability of the expanded CAG tract during intergenerational transmissions.

Huntington's disease (HD) is due to dominant expansions of the CAG repeat of the HTT gene. Meiotic instability of the (CAG)n might impact the disorder frequency. We report on HD minimal prevalence in Rio Grande do Sul (RS) state, Brazil, and on intergenerational instability of the (CAG)n in HD families. Symptomatic and at-risk subjects from 179 HD families were ascertained between 2013 and 2016. Clinical, molecular and family history data were obtained. Expanded (CAG)n length differences between parent and child (delta-expanded-(CAG)n) were calculated. Effect of parental age on the (CAG)n instability upon transmission was inferred by correlating delta-expanded-(CAG)n between siblings to their age differences. HD minimal prevalence in RS state was estimated as 1.85:100,000 inhabitants. Alleles with (CAG)27-35 were found on 21/384 non-disease associated chromosomes (5.5%); among 253 expanded alleles, four (1.6%) were within reduced penetrance range with (CAG)36-39. In 32 direct transmissions, mean instability was larger among paternal than maternal transmissions. In direct transmissions and in 51 sibling pairs, parental age at the time of child birth were not correlated with delta-expanded-(CAG)n. Briefly, HD prevalence in RS state was lower than those reported for European populations. Expanded (CAG)n transmissions were unstable and not associated to parental age.