Clinical and epidemiological aspects of severe acute respiratory infection: before and during the first year of the COVID-19 pandemic in Brazil.

BACKGROUND: Widespread respiratory infections with high morbidity rates caused by respiratory viruses represent a significant global public health problem. Our objective was to describe cases and deaths from severe acute respiratory infection (SARI) in Brazil over the past 8 y as well as changes in the distribution and risk of illness and death from SARI before and in the first year of the coronavirus disease 2019 (COVID-19) pandemic (FYP). METHODS: We performed a descriptive epidemiological study of hospitalized SARI cases and deaths between 2013 and 2020 in Brazil, separated into pre-pandemic (2013 to 2019) and FYP (2020). We estimate the increase in SARI cases and deaths in the FYP as well as the mortality and infection risks attributable to the FYP (MRAP and IRAP, respectively). RESULTS: In 2020, an excess of 425 054 cases and 109 682 deaths was observed, with a significant increase in the risk of falling ill and dying from SARI, with an IRAP of 200.06 and an MRAP of 51.68 cases per 100 000 inhabitants. The increase in SARI cases and deaths was particularly prominent among patients with COVID-19, the elderly, males, those self-identifying as mixed race and patients with heart disease and diabetes. We conclude that an important increase in morbidity and mortality due to SARI was observed in the FYP. More vulnerable groups and those living in the Southeast, North and Center-West regions of the country suffered the most.

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.

Analysis of Viral and Host Factors on Immunogenicity of 2018, 2019, and 2020 Southern Hemisphere Seasonal Trivalent Inactivated Influenza Vaccine in Adults in Brazil.

Annual vaccination against influenza is the best tool to prevent deaths and hospitalizations. Regular updates of trivalent inactivated influenza vaccines (TIV) are necessary due to high mutation rates in influenza viruses. TIV effectiveness is affected by antigenic mismatches, age, previous immunity, and other host factors. Studying TIV effectiveness annually in different populations is critical. The serological responses to Southern-Hemisphere TIV and circulating influenza strains were evaluated in 2018-2020 among Brazilian volunteers, using hemagglutination inhibition (HI) assays. Post-vaccination titers were corrected to account for pre-vaccination titers. Our population achieved >83% post-vaccination seroprotection levels, whereas seroconversion rates ranged from 10% to 46%. TIV significantly enhanced antibody titers and seroprotection against all prior and contemporary vaccine and circulating strains tested. Strong cross-reactive responses were detected, especially between H1N1 subtypes. A/Singapore/INFIMH-16-0019/2016, included in the 2018 TIV, induced the poorest response. Significant titer and seroprotection reductions were observed 6 and 12 months after vaccination. Age had a slight effect on TIV response, whereas previous vaccination was associated with lower seroconversion rates and titers. Despite this, TIV induced high seroprotection for all strains, in all groups. Regular TIV evaluations, based on regional influenza strain circulation, should be conducted and the factors affecting response studied.

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.

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.

Retrospective cohort of children and adolescents hospitalized by COVID-19 in Brazil from the beginning of the pandemic to August 1st, 2020. / Coorte retrospectiva de crianças e adolescentes hospitalizados por COVID-19 no Brasil do início da pandemia a 1º de agosto de 2020.

OBJECTIVES: To characterize the study population, estimating the in-hospital lethality rate by state and analysing associated factors with COVID-19-related deaths. METHODS: A retrospective cohort study was carried out of hospitalised children and adolescents diagnosed with COVID-19, confirmed by RT-PCR, whose outcome was death by COVID-19 or recovery, from 2020 March 1 to August 1. The data source was the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe in Brazilian acronym), where patients with Severe Acute Respiratory Syndrome (SARS) are notified. Children were defined as those between the ages of 0 and 11, and adolescents those between 12 and 18. A bi and multivariate analysis were performed using Poisson Regression with robust variance, with adjusted Relative Risk as the final association measure. RESULTS: A total of 4,930 cases were analysed; 2,553 (51.8%) were males, 2,335 (47.4%) were brown-skinned. The Federative Unit of Roraima presented the highest in-hospital case-fatality rate, with 68.8% (11/16). Multivariate analysis showed that belonging to the age group adolescent (RR = 1.59; 95%CI 1.12 - 2.25; p = 0.009), SARS-critical patient (RR = 4.56; 95%CI 2, 77 - 7.51; p < 0.001) and presenting immunological disorders (RR = 2.24; 95%CI 1.58 - 3.17; p < 0.001) as comorbidities were statistically associated factors with death by COVID-19. CONCLUSION: It was observed that adolescents, SARS-critical patients, and presence of immunological disorders were important factors associated with death. Active surveillance and differentiated care are recommended for patients with chronic diseases and special immunological conditions.

OBJETIVOS: Caracterizar a população do estudo, estimar a taxa de letalidade intra-hospitalar por estado e analisar fatores associados aos óbitos por COVID-19. MÉTODOS: Foi realizado estudo de coorte retrospectiva de crianças e adolescentes hospitalizados com diagnóstico de COVID-19 confirmado por transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR), tendo como desfecho óbito por COVID-19 ou recuperação, entre 1º de março e 1º de agosto de 2020. A fonte de dados foi o Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe), ao qual são notificados pacientes internados com Síndrome Respiratória Aguda Grave (SRAG). Consideraram-se crianças os pacientes com idade entre 0 e 11 anos completos e adolescentes aqueles com idade entre 12 e 18 anos completos. Realizou-se análise bi e multivariável por meio de Regressão de Poisson com variância robusta, utilizando-se como medida de associação final o Risco Relativo ajustado (RRa). RESULTADOS: Dos 4.930 casos analisados, 2.553 (51,8%) eram do sexo masculino. A raça/cor autodeclarada parda foi a mais frequente, com 2.335 (47,4%). A unidade federativa de Roraima apresentou a maior taxa de letalidade intra-hospitalar, com 68,8% (n = 11/16). A análise multivariada mostrou que pertencer ao grupo etário adolescente (RR = 1,59; IC95% 1,12 - 2,25; p = 0,009), ter sido classificado como SRAG-crítico (RR = 4,56; IC95% 2,77 - 7,51; p < 0,001) e apresentar imunopatia (RR = 2,24; IC95% 1,58 - 3,17; p < 0,001) como comorbidade configuraram-se como fatores associados ao óbito pela COVID-19. CONCLUSÃO: Observou-se que ser adolescente, ter classificação de SRAG-crítico e imunopatia como comorbidade foram importantes fatores associados ao óbito. Recomenda-se vigilância ativa e cuidados diferenciados a portadores de doenças crônicas e condições imunológicas especiais.

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.

Severe Acute Respiratory Syndrome Coronavirus 2 P.2 Lineage Associated with Reinfection Case, Brazil, June-October 2020.

A 37-year-old healthcare worker from the northeastern region of Brazil experienced 2 clinical episodes of coronavirus disease. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by reverse transcription PCR in samples collected 116 days apart. Whole-genome sequencing revealed that the 2 infections were caused by the most prevalent lineage in Brazil, B.1.1.33, and the emerging lineage P.2. The first infection occurred in June 2020; Bayesian analysis suggests reinfection at some point during September 14-October 11, 2020, a few days before the second episode of coronavirus disease. Of note, P.2 corresponds to an emergent viral lineage in Brazil that contains the mutation E484K in the spike protein. The P.2 lineage was initially detected in the state of Rio de Janeiro, and since then it has been found throughout the country. Our findings suggest not only a reinfection case but also geographic dissemination of the emerging Brazil clade P.2.

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.

Description of COVID-19 hospitalized health worker cases in the first nine weeks of the pandemic, Brazil, 2020. / Descrição dos casos hospitalizados pela COVID-19 em profissionais de saúde nas primeiras nove semanas da pandemia, Brasil, 2020.

OBJECTIVE: To describe COVID-19 hospitalized health worker cases in Brazil. METHODS: This was a descriptive case series study; it included cases that became ill between February 21st and April 15th, 2020 registered on the Influenza Surveillance Information System (SIVEP-Gripe, acronym in Portuguese). RESULTS: Of the 184 cases, 110 (59.8%) were female and median age was 44 years (min-max: 23-85); 89 (48.4%) were nursing professionals and 50 (27.2%) were doctors. Ninety-two (50.0%) presented comorbidity, with heart disease predominating (n=37; 40.2%). Of the 112 professionals with a record of case progression, 85 (75.9%) were cured and 27 (24.1%) died, 18 of whom were male. CONCLUSION: The profile of COVID-19 hospitalized health workers is similar to that of the general population with regard to age and comorbidities, but different in relation to sex. The most affected areas were nursing and medicine.

Descripción de los casos hospitalizados por COVID-19 en profesionales de salud en las primeras nueve semanas de la pandemia, Brasil, 2020 Description of COVID-19 hospitalized health worker cases in the first nine weeks of the pandemic, Brazil, 2020

Resumo Objetivo: Descrever os casos hospitalizados pela COVID-19 em profissionais de saúde no Brasil. Métodos: Estudo descritivo de tipo série de casos;foram incluídos aqueles com adoecimento entre 21 de fevereiro e 15 de abril de 2020, registrados no Sistema de Informação de Vigilância da Gripe (SIVEP-Gripe). Resultados: Dos 184 casos, 110 (59,8%) eram do sexo feminino, com mediana de idade de 44 anos (mínima-máxima: 23-85);89 (48,4%) eram profissionais da enfermagem e 50 (27,2%) eram médicos. Ainda, 92 (50,0%) apresentavam comorbidade, predominando cardiopatias (n=37;40,2%). Dos 112 profissionais com registro de evolução, 85 (75,9%) alcançaram cura e 27 (24,1%) foram a óbito, 18 destes do sexo masculino. Conclusão: O perfil dos profissionais de saúde hospitalizados por COVID-19 é semelhante ao da população quanto à idade e comorbidades;porém, diferente quanto ao sexo. As áreas profissionais mais acometidas foram a enfermagem e a medicina. Resumen Objetivo: Describir los casos hospitalizados por COVID-19 en profesionales de salud, en Brasil. Métodos: Estudio descriptivo del tipo serie de casos;se incluyeron aquellos que enfermaron entre el 21 de febrero y el 15 de abril de 2020, registrados en el Sistema de Información de Vigilancia de la Gripe (SIVEP-Gripe). Resultados: De los 184 (1,76%) casos 110 (59,8%) eran del sexo femenino, con promedio de edad de 44 años (mínima-máxima: 23-85), 89 (48,4%) eran profesionales de enfermería y 50 (27,2%) médicos. Además, 92 (50,0%) presentaron comorbilidad, predominando las cardiopatías (n=37;40,2%). De los 112 profesionales con un historial de evolución, 85 (75,9%) fueron curados y 27 (24,1%) murieron, 18 de los cuales era de sexo masculino. Conclusión: El perfil de los hospitalizados por COVID-19 es similar al de la población en edad y comorbilidades, aunque diferente con relación a sexo. Las áreas más afectadas fueron la enfermería y la medicina. Objective: To describe COVID-19 hospitalized health worker cases in Brazil. Methods: This was a descriptive case series study;it included cases that became ill between February 21st and April 15th, 2020 registered on the Influenza Surveillance Information System (SIVEP-Gripe, acronym in Portuguese). Results: Of the 184 cases, 110 (59.8%) were female and median age was 44 years (min-max: 23-85);89 (48.4%) were nursing professionals and 50 (27.2%) were doctors. Ninety-two (50.0%) presented comorbidity, with heart disease predominating (n=37;40.2%). Of the 112 professionals with a record of case progression, 85 (75.9%) were cured and 27 (24.1%) died, 18 of whom were male. Conclusion: The profile of COVID-19 hospitalized health workers is similar to that of the general population with regard to age and comorbidities, but different in relation to sex. The most affected areas were nursing and medicine.

Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.