Spatiotemporal dynamics and epidemiological impact of SARS-CoV-2 XBB lineage dissemination in Brazil in 2023.

The SARS-CoV-2 XBB is a group of highly immune-evasive lineages of the Omicron variant of concern that emerged by recombining BA.2-descendent lineages and spread worldwide during 2023. In this study, we combine SARS-CoV-2 genomic data (n = 11,065 sequences) with epidemiological data of severe acute respiratory infection (SARI) cases collected in Brazil between October 2022 and July 2023 to reconstruct the space-time dynamics and epidemiologic impact of XBB dissemination in the country. Our analyses revealed that the introduction and local emergence of lineages carrying convergent mutations within the Spike protein, especially F486P, F456L, and L455F, propelled the spread of XBB* lineages in Brazil. The average relative instantaneous reproduction numbers of XBB* + F486P, XBB* + F486P + F456L, and XBB* + F486P + F456L + L455F lineages in Brazil were estimated to be 1.24, 1.33, and 1.48 higher than that of other co-circulating lineages (mainly BQ.1*/BE*), respectively. Despite such a growth advantage, the dissemination of these XBB* lineages had a reduced impact on Brazil's epidemiological scenario concerning previous Omicron subvariants. The peak number of SARI cases from SARS-CoV-2 during the XBB wave was approximately 90%, 80%, and 70% lower than that observed during the previous BA.1*, BA.5*, and BQ.1* waves, respectively. These findings revealed the emergence of multiple XBB lineages with progressively increasing growth advantage, yet with relatively limited epidemiological impact in Brazil throughout 2023. The XBB* + F486P + F456L + L455F lineages stand out for their heightened transmissibility, warranting close monitoring in the months ahead. IMPORTANCE: Brazil was one the most affected countries by the SARS-CoV-2 pandemic, with more than 700,000 deaths by mid-2023. This study reconstructs the dissemination of the virus in the country in the first half of 2023, a period characterized by the dissemination of descendants of XBB.1, a recombinant of Omicron BA.2 lineages evolved in late 2022. The analysis supports that XBB dissemination was marked by the continuous emergence of indigenous lineages bearing similar mutations in key sites of their Spike protein, a process followed by continuous increments in transmissibility, and without repercussions in the incidence of severe cases. Thus, the results suggest that the epidemiological impact of the spread of a SARS-CoV-2 variant is influenced by an intricate interplay of factors that extend beyond the virus's transmissibility alone. The study also underlines the need for SARS-CoV-2 genomic surveillance that allows the monitoring of its ever-shifting composition.

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.

Severity of influenza illness by seasonal influenza vaccination status among hospitalised patients in four South American countries, 2013-19: a surveillance-based cohort study.

BACKGROUND: Although several studies have reported attenuated influenza illness following influenza vaccination, results have been inconsistent and have focused predominantly on adults in the USA. This study aimed to evaluate the severity of influenza illness by vaccination status in a broad range of influenza vaccine target groups across multiple South American countries. METHODS: We analysed data from four South American countries (Argentina, Brazil, Chile, and Paraguay) participating in REVELAC-i, a multicentre, test-negative design, vaccine effectiveness network including 41 sentinel hospitals. Individuals hospitalised at one of these centres with severe acute respiratory infection were tested for influenza by real-time RT-PCR, and were included in the analysis if they had complete information about their vaccination status and outcomes of their hospital stay. We used multivariable logistic regression weighted by inverse probability of vaccination and adjusted for antiviral use, duration of illness before admission, and calendar week, to calculate the adjusted odds ratios (aORs) of intensive care unit (ICU) admission and in-hospital death (and combinations of these outcomes) among influenza-positive patients by vaccination status for three target groups: young children (aged 6-24 months), adults (aged 18-64 years) with pre-existing health conditions, and older adults (aged ≥65 years). Survival curves were used to compare length of hospital stay by vaccination status in each target group. FINDINGS: 2747 patients hospitalised with PCR-confirmed influenza virus infection between Jan 1, 2013, and Dec 8, 2019, were included in the study: 649 children (70 [10·8%] fully vaccinated, 193 [29·7%] partially vaccinated) of whom 87 (13·4%) were admitted to ICU and 12 (1·8%) died in hospital; 520 adults with pre-existing medical conditions (118 [22·7%] vaccinated), of whom 139 (26·7%) were admitted to ICU and 55 (10·6%) died in hospital; and 1578 older adults (609 [38·6%] vaccinated), of whom 271 (17·2%) were admitted to ICU and 220 (13·9%) died in hospital. We observed earlier discharge among partially vaccinated children (adjusted hazard ratio 1·14 [95% CI 1·01-1·29]), fully vaccinated children (1·24 [1·04-1·47]), and vaccinated adults with pre-existing medical conditions (1·78 [1·18-2·69]) compared with their unvaccinated counterparts, but not among vaccinated older adults (0·82 [0·65-1·04]). Compared with unvaccinated individuals, lower odds of ICU admission were found for partially vaccinated children (aOR 0·64 [95% CI 0·44-0·92]) and fully vaccinated children (0·52 [0·28-0·98]), but not for adults with pre-existing conditions (1·25 [0·93-1·67]) or older adults (0·88 [0·72-1·08]). Lower odds of in-hospital death (0·62 [0·50-0·78]) were found in vaccinated versus unvaccinated older adults, with or without ICU admission, but did not differ significantly in partially vaccinated (1·35 [0·57-3·20]) or fully vaccinated young children (0·88 [0·16-4·82]) or adults with pre-existing medical conditions (1·09 [0·73-1·63]) compared with the respective unvaccinated patient groups. INTERPRETATION: Influenza vaccination was associated with illness attenuation among those hospitalised with influenza, although results differed by vaccine target group. These findings might suggest that attenuation of disease severity might be specific to certain target groups, seasons, or settings. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

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.

Low prevalence of influenza A strains with resistance markers in Brazil during 2017-2019 seasons.

The influenza A virus (IAV) is of a major public health concern as it causes annual epidemics and has the potential to cause pandemics. At present, the neuraminidase inhibitors (NAIs) are the most widely used anti-influenza drugs, but, more recently, the drug baloxavir marboxil (BXM), a polymerase inhibitor, has also been licensed in some countries. Mutations in the viral genes that encode the antiviral targets can lead to treatment resistance. Worldwide, a low prevalence of antiviral resistant strains has been reported. Despite that, this situation can change rapidly, and resistant strain surveillance is a priority. Thus, the aim of this was to evaluate Brazilian IAVs antiviral resistance from 2017 to 2019 through the identification of viral mutations associated with reduced inhibition of the drugs and by testing the susceptibility of IAV isolates to oseltamivir (OST), the most widely used NAI drug in the country. Initially, we analyzed 282 influenza A(H1N1)pdm09 and 455 A(H3N2) genetic sequences available on GISAID. The amino acid substitution (AAS) NA:S247N was detected in one A(H1N1)pdm09 strain. We also identified NA:I222V (n = 6) and NA:N329K (n = 1) in A(H3N2) strains. In addition, we performed a molecular screening for NA:H275Y in 437 A(H1N1)pdm09 samples, by pyrosequencing, which revealed a single virus harboring this mutation. Furthermore, the determination of OST IC50 values for 222 A(H1N1)pdm09 and 83 A(H3N2) isolates revealed that all isolates presented a normal susceptibility profile to the drug. Interestingly, we detected one A(H3N2) virus presenting with PA:E119D AAS. Moreover, the majority of the IAV sequences had the M2:S31N adamantanes resistant marker. In conclusion, we show a low prevalence of Brazilian IAV strains with NAI resistance markers, in accordance with what is reported worldwide, indicating that NAIs still remain an option for the treatment of influenza infections in Brazil. However, surveillance of influenza resistance should be strengthened in the country for improving the representativeness of investigated viruses and the robustness of the analysis.

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.

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.

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.

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.

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.

The Global Epidemiology of RSV in Community and Hospitalized Care: Findings From 15 Countries.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infections. To optimize control strategies, a better understanding of the global epidemiology of RSV is critical. To this end, we initiated the Global Epidemiology of RSV in Hospitalized and Community care study (GERi). METHODS: Focal points from 44 countries were approached to join GERi and share detailed RSV surveillance data. Countries completed a questionnaire on the characteristics of their surveillance system. RESULTS: Fifteen countries provided granular surveillance data and information on their surveillance system. A median (interquartile range) of 1641 (552-2415) RSV cases per season were reported from 2000 and 2020. The majority (55%) of RSV cases occurred in the <1-year-olds, with 8% of cases reported in those aged ≥65 years. Hospitalized cases were younger than those in community care. We found no age difference between RSV subtypes and no clear pattern of dominant subtypes. CONCLUSIONS: The high number of cases in the <1-year-olds indicates a need to focus prevention efforts in this group. The minimal differences between RSV subtypes and their co-circulation implies that prevention needs to target both subtypes. Importantly, there appears to be a lack of RSV surveillance data in the elderly.

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.

Defining the seasonality of respiratory syncytial virus around the world: National and subnational surveillance data from 12 countries.

BACKGROUND: Respiratory syncytial virus (RSV) infections are one of the leading causes of lower respiratory tract infections and have a major burden on society. For prevention and control to be deployed effectively, an improved understanding of the seasonality of RSV is necessary. OBJECTIVES: The main objective of this study was to contribute to a better understanding of RSV seasonality by examining the GERi multi-country surveillance dataset. METHODS: RSV seasons were included in the analysis if they contained ≥100 cases. Seasonality was determined using the "average annual percentage" method. Analyses were performed at a subnational level for the United States and Brazil. RESULTS: We included 601 425 RSV cases from 12 countries. Most temperate countries experienced RSV epidemics in the winter, with a median duration of 10-21 weeks. Not all epidemics fit this pattern in a consistent manner, with some occurring later or in an irregular manner. More variation in timing was observed in (sub)tropical countries, and we found substantial differences in seasonality at a subnational level. No association was found between the timing of the epidemic and the dominant RSV subtype. CONCLUSIONS: Our findings suggest that geographical location or climatic characteristics cannot be used as a definitive predictor for the timing of RSV epidemics and highlight the need for (sub)national data collection and analysis.

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.

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% (n=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 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, confirmados por RT-PCR, tendo como desfecho óbito por COVID-19 ou recuperado, entre 1º de março a 1º de agosto de 2020. A fonte de dados foi Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe), onde são notificados pacientes internados com Síndrome Respiratória Aguda Grave (SRAG). Considerou-se crianças aqueles 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, sendo utilizado 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). 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 se configuraram 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 crónicas e condições imunológicas especiais.