Genomic characterization of Influenza A (H1N1)pdm09 and SARS-CoV-2 from Influenza Like Illness (ILI) and Severe Acute Respiratory Illness (SARI) cases reported between July-December, 2022.

Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) cases are more prone to Influenza and SARS-CoV-2 infection. Accordingly, we genetically characterized Influenza and SARS-CoV-2 in 633 ILI and SARI cases by rRT-PCR and WGS. ILI and SARI cases showed H1N1pdm09 prevalence of 20.9% and 23.2% respectively. 135 (21.3%) H1N1pdm09 and 23 (3.6%) H3N2 and 5 coinfection (0.78%) of H1N1pdm09 and SARS-CoV-2 were detected. Phylogenetic analysis revealed H1N1pdm09 resemblance to clade 6B.1A.5a.2 and their genetic relatedness to InfA/Perth/34/2020, InfA/Victoria/88/2020 and InfA/Victoria/2570/2019. Pan 24 HA and 26 NA nonsynonymous mutations and novel HA (G6D, Y7F, Y78H, P212L, G339R, T508K and S523T) and NA (S229A) mutations were observed. S74R, N129D, N156K, S162N, K163Q and S164T alter HA Cb and Sa antibody recognizing site. Similarly, M19T, V13T substitution and multiple mutations in transmembrane and NA head domain drive antigenic drift. SARS-CoV-2 strains genetically characterized to Omicron BA.2.75 lineage containing thirty nonsynonymous spike mutations exhibited enhanced virulence and transmission rates. Coinfection although detected very minimal, the mutational changes in H1N1pdm09 and SARS-CoV-2 virus infected individuals could alter antibody receptor binding sites, allowing the viruses to escape immune response resulting in better adaptability and transmission. Thus continuous genomic surveillance is required to tackle any future outbreak.

Individual and contextual factors associated with the survival of patients with severe acute respiratory syndrome by COVID-19 in Brazil.

OBJECTIVE: To analyze the influence of individual and contextual factors of the hospital and the municipality of care on the survival of patients with Severe Acute Respiratory Syndrome due to COVID-19. METHODS: Hospital cohort study with data from 159,948 adults and elderly with Severe Acute Respiratory Syndrome due to COVID-19 hospitalized from January 1 to December 31, 2022 and reported in the Influenza Epidemiological Surveillance Information System. The contextual variables were related to the structure, professionals and equipment of the hospital establishments and socioeconomic and health indicators of the municipalities. The outcome was hospital survival up to 90 days. Survival tree and Kaplan-Meier curves were used for survival analysis. RESULTS: Hospital lethality was 30.4%. Elderly patients who underwent invasive mechanical ventilation and were hospitalized in cities with low tax collection rates had lower survival rates compared to other groups identified in the survival tree (p<0.001). CONCLUSION: The study indicated the interaction of contextual factors with the individual ones, and it shows that hospital and municipal characteristics increase the risk of death, highlighting the attention to the organization, operation, and performance of the hospital network.

Proporção de casos nosocomiais de COVID-19 no Brasil: análise de seus fatores associados em 1.631.47 registros de 2020 a 2022 / Proporción de casos nosocomiales de COVID-19 en Brasil: análisis de sus factores asociados en 1.631.47 registros de 2020 a 2022 / Proportionof nosocomial cases of COVID-19 in Brazil: analysisof1.631.47 case records from 2020 to 2022

Introdução: Infecções nosocomiais, adquiridas após a internação hospitalar, são o evento adverso mais comum que ameaça a saúde dos pacientes hospitalizados, sendo a pneumonia, incluindo a causada pelo SARS-Cov-2, responsável por mais de 80% das infecções nosocomiais. A pandemia declarada pela OMS em março de 2020 reflete o rápido aumento de casos, impulsionado pela disseminação do vírus através de gotículas e aerossóis. A transmissão nosocomial do SARS-Cov-2 foi observada desde o início do surto em Wuhan, representando um desafio adicional na qualidade de vida dos pacientes. Estudos internacionais em hospitais reportam incidências de infecção nosocomial por COVID-19 entre 11% e 44%.Objetivo: Identificar a proporção de infecção nosocomial por SARS-COV-2 no Brasil entre março de 2020 até dezembro de 2022.Metodologia:Trata-se de um estudo analítico, retrospectivo, de corte transversal, sobre a proporção de infecção nosocomial por Sars-Cov-2 no Brasil, através de dados secundários oriundos do Sistema de Informação da Vigilância Epidemiológica da Gripe. No presente estudo a variável dependente analisada foi a proporção de infecção nosocomial por Sars-cov-2. Como variáveis independentes exploratórias foram utilizadas: faixa etária, sexo, comorbidades e macrorregião de residência. Resultados: O estudo identificou uma proporção de casos nosocomiais de 2,58%, sendo maior no terceiro ano da pandemia 2022 (5,5%) na região Norte (7,57%), entre os indivíduos de 18-59 anos de idade (6,93%)Conclusões: Este estudo sobre casos nosocomiais de COVID-19 no Brasil revela uma proporção de 2,58% entre 2020 e 2022, com associações identificadas em relação à região, idade e comorbidades. Diferenças em relação a estudos internacionais sugerem questões metodológicas específicas. Essa pesquisa é de importância crítica, visto ser de abrangência nacional com grande amplitude, e estabelece uma base sólida para futuros estudos epidemiológicos (AU).

Introduction: Nosocomial infections, acquired after hospital admission, are the most common adverse events threatening patient health, with pneumonia, including that caused by SARS-CoV-2, responsible for over 80% of nosocomial infections. The pandemic declared by the WHO in March 2020 reflects the rapid rise in cases driven by the virus's spread through droplets and aerosols. Nosocomial transmission of SARS-CoV-2 has been observed since the outbreak's onset in Wuhan, posing an additional challenge to patient quality of life. International hospital studies report nosocomial COVID-19 infection rates between 11% and 44%. Objective: Identifying the proportion of nosocomial SARS-CoV-2 infection in Brazil between March 2020 and December 2022.Methodology:This is an analytical, retrospective, cross-sectional study on the proportion of nosocomial SARS-CoV-2 infection in Brazil, using secondary data from the Influenza Epidemiological Surveillance Information System. In this study, the analyzed dependent variable was the proportionof nosocomial SARS-CoV-2 infection. The exploratory independent variables included: age group, gender, comorbidities, and macro-region of residence.Results:The study identified a proportion of nosocomial cases of 2.58%, with a higher proportion in the third year of the pandemic, 2022 (5.5%) in the North region (7.57%), among individuals aged 18-59 years (6.93%). Conclusions: This study on nosocomial cases of COVID-19 in Brazil reveals a proportion of 2.58% between 2020 and 2022, with associations identified regarding region, age, and comorbidities. Differences compared to international studies suggest specific methodological issues. This research is of critical importance, given its national scope and broad coverage, and establishes a solid foundation for future epidemiological studies (AU).

Introducción: Las infecciones nosocomiales, adquiridas tras la hospitalización, son el evento adverso más común que amenaza la salud de los pacientes hospitalizados, siendo la neumonía, incluida la causada por el SARS-Cov-2, la responsable de más del 80% de las infecciones. La pandemia declarada por la OMS en marzo de 2020 refleja el rápido aumento de casos, impulsado por la propagación del virus a través de gotitas y aerosoles. La transmisión nosocomial del SRAS-Cov-2 se ha observado desde el inicio del brote en Wuhan, lo que supone un reto adicional para la calidad de vida de los pacientes. Estudios internacionales realizados en hospitales informan de incidencias de infecciones nosocomiales por COVID-19 de entre el 11% y el 44%. Objetivo: Identificar la proporción de infección nosocomial por SARS-CoV-2 en Brasil entre marzo de 2020 y diciembre de 2022. Metodología: Se trata de un estudio analítico, retrospectivo y transversal sobre la proporción de infección nosocomial por SARS-CoV -2 en Brasil, utilizando datos secundarios del Sistema de Información de Vigilancia Epidemiológica de Influenza. La variable dependiente analizada fue la proporción de infección nosocomial por SARS-CoV-2. Como variables independientes exploratorias se utilizaron: grupo de edad, sexo, comorbilidades y macrorregión de residencia. Resultados:El estudio identificó una proporción de casos nosocomiales del 2,58%, siendo mayor en el tercer año de la pandemia de 2022 (5,5%) en la región Norte (7,57%), entre individuos de 18 a 59 años (6,93%). Conclusiones:Este estudio de casos de COVID-19 hospitalizados en Brasil revela una proporción de 2,58% entre 2020 y 2022, con asociaciones identificadas en relación a la región, edad y comorbilidades. Las disparidades en relación a estudios internacionales sugieren la presencia de cuestiones metodológicas específicas. Esta investigación es de extrema importancia para orientar estrategias preventivas y mejorar el control de las infecciones hospitalarias (AU).

Virus removal by high-efficiency air (HEPA) filters and filtration capacity enhancement by nanotextiles: a pilot study.

Portable household air purifiers are widely used devices designed to maintain a high-quality level of indoor air. Portable air purifiers equipped with the high-efficiency air (HEPA) filter served 100 h in a household space occupied by two adults without any symptoms of respiratory tract infection. The main objective of the study was to determine microbial contamination on the HEPA filter and to investigate if the selected nanotextile monolayer made of polyamide 6 (PA6) nanofibers can capture potential microorganisms when installed downstream of the HEPA filter as the final filtration medium. Samples were taken from the inlet and outlet surfaces. Samples from the nanotextile were collected in the same manner as from the HEPA filter. QIAStat DX® 1.0 Analyzer using the Respiratory SARS CoV-2 Panel multiplex PCR detection system was selected for microorganism detection. Adenovirus was detected on the inlet surface of the HEPA filter. The outlet surface of the filter contained no viruses included in the Respiratory SARS CoV-2 Panel portfolio. The nanotextile monolayer was replaced twice during the 100 h of operation, so three pieces were used and all contained coronavirus 229 E. Coronavirus 229 E was then detected in the nasopharynx of one of the members of the household as well. It may be assumed that the selected nanotextile is capable of capturing a virus of a small size.

Multimerization of the heptad repeat regions of the SARS-CoV 2 spike protein.

The heptad repeat 1 and 2 (HR1, HR2) regions in the spike protein of SARS-CoV 2 play a key role in the fusogenic mechanism of the virus with the host cell. During the fusion process they are thought to rearrange into an interdomain multimer. Functional fragments of the heptad repeat 1 and 2 regions in the spike protein of SARS-CoV 2 were chemically synthesized, labeled with nitrofurazone (NBD) and their interactions investigated by fluorescence spectroscopy. Steady state emission, fluorescence quenching, anisotropy and lifetime measurements in combination with a fluorophore dilution scheme were used to dissect multimer formation of HR1 and HR2 in quantitative detail. In addition, the investigation of the multimers by homo-FRET (via anisotropy) and lifetime measurements reveals new insights into the mechanism of fluorophore-fluorophore interactions in biological samples.

Comparative analysis of Respiratory Syncytial Virus frequency rates and viral load in different patient cohorts in a University Hospital in São Paulo, Brazil, over an eight-year period (2005-2013).

Respiratory Syncytial Virus (RSV) poses a global health concern, particularly affecting young children, the elderly, and immunosuppressed individuals. RSV viral load is essential for understanding transmission, disease severity, prevention, and treatment. This retrospective study aimed to analyze the frequency rates and viral loads of RSV infections in different patient cohorts and age groups over an eight-year period in a university hospital in São Paulo, Brazil. This study analyzed 1380 Immunocompetent (IC) and Immunosuppressed (IS) patients with acute respiratory tract infections. IC included patients with chronic Heart Disease (HD), Primary Care service recipients (PC), and a subgroup suspected of having Severe Acute Respiratory Syndrome caused by Influenza A (H1N1)pdm09 virus (SARS H1N1). IS comprised transplant patients and those with HIV infection. Respiratory samples were collected between February 2005 and October 2013, with RSV detection and viral load quantification (Log10 copies of RNA/mL) using RT-qPCR. Overall RSV infection rate was 17.3 %, with higher rates in children (23.9 %) than in adults (12.9 %), particularly in children under two years of age (28.2 %). Children in the SARS H1N1 and PC subgroups had higher infection rates (16.4 % and 34.9 %, respectively), with the highest rate in PC children aged 1 to < 2 years (45.45 %). Adults with HD had a significantly higher frequency rate (27.83 %) than those in the SARS H1N1 (2.65 %) and IS (15.16 %) subgroups and higher hospitalization rate among adults under 65 years. RSV viral load ranged from 2.43 to 10.15 Log10 RNA copies/mL (mean ± SD 5.82 ± 2.19), with hospitalized patients exhibiting significantly higher viral loads (7.34 ± 1.9) than outpatients (4.38 ± 1.89). Elderly bone marrow transplant patients also had significantly higher viral loads (7.57 ± 2.41) than younger adults (5.12 ± 1.87). This study provides insights into the RSV infection patterns in different patient cohorts in Brazil. Further investigations are needed to understand susceptibility and risk factors associated with RSV infection. In conclusion, high RSV viral load among hospitalized patients could serve as a surrogate marker of disease severity. Additionally, patients with chronic heart disease deserve greater attention regarding complications associated with RSV infection.

Development, Histological, and Ultrastructural Evaluation of Sheep Hyperimmune Serum Therapy for COVID-19 / Desarrollo, Evaluación Histológica y Ultraestructural de la Terapia con Suero Hiperinmune de Oveja para COVID-19

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

A comprehensive dataset of animal-associated sarbecoviruses.

Zoonotic spillover of sarbecoviruses (SarbeCoVs) from non-human animals to humans under natural conditions has led to two large-scale pandemics, the severe acute respiratory syndrome (SARS) pandemic in 2003 and the ongoing COVID-19 pandemic. Knowledge of the genetic diversity, geographical distribution, and host specificity of SarbeCoVs is therefore of interest for pandemic surveillance and origin tracing of SARS-CoV and SARS-CoV-2. This study presents a comprehensive repository of publicly available animal-associated SarbeCoVs, covering 1,535 viruses identified from 63 animal species distributed in 43 countries worldwide (as of February 14,2023). Relevant meta-information, such as host species, sampling time and location, was manually curated and included in the dataset to facilitate further research on the potential patterns of viral diversity and ecological characteristics. In addition, the dataset also provides well-annotated sequence sets of receptor-binding domains (RBDs) and receptor-binding motifs (RBMs) for the scientific community to highlight the potential determinants of successful cross-species transmission that could be aid in risk estimation and strategic design for future emerging infectious disease control and prevention.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18-70 Years; A Randomized, Double-Blind Clinical Trial.

BACKGROUND: This study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. METHOD: In a randomized, double-blind, placebo-controlled trial, adults aged 18-70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. RESULT: Between May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02-6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. CONCLUSION: RCP vaccine is safe and creates strong and durable humoral and cellular immunity. TRIAL REGISTRATION: (IRCT20201214049709N2).

Clinical and sociodemographic aspects of cases of severe acute respiratory syndrome in southern Brazil / Aspectos clínicos e sociodemográficos dos casos de Síndrome Respiratória Aguda Grave no sul do Brasil / Aspectos clínicos y sociodemográficos de casos de Síndrome Respiratorio Agudo Severo en el sur de Brasil

Background and objectives: to compare the clinical and sociodemographic aspects of individuals with SARS reported in the countryside of Rio Grande do Sul in 2020 and 2021. Methods: a cross-sectional study, from March 2020 to October 2021. Clinical and sociodemographic variables of individuals with SARS symptoms were analyzed, compared through descriptive, univariate analyses, according to the year of reporting. Results: a total of 4,710 cases of SARS were reported; 53.4% were SARS related to COVID-19 in 2020 and 87.5% in 2021 (p<0.001). Comparing 2020 and 2021, the sociodemographic profile changed in terms of age group, skin color and education (p<0.001). Regarding clinical aspects, there was a reduction in prevalence of pre-existing health conditions, except obesity, changes in reported signs and symptoms and reduction in hospital and Intensive Care Unit admissions. Conclusion: the changes in the profile may reflect the effect of the different variants and the start of immunization for SARS-CoV-2.(AU)

Justificativa e objetivos: comparar, entre os anos de 2020 e 2021, os aspectos clínicos e sociodemográficos dos indivíduos com Síndrome Respiratória Aguda Grave (SRAG) notificados em uma região de saúde do interior do Rio Grande do Sul. Métodos: estudo transversal descritivo, realizado de março de 2020 a outubro de 2021. Foram analisadas variáveis clínicas e sociodemográficas de indivíduos com sintomas de SRAG, comparadas através de análises descritivas, univariadas, conforme o ano de notificação. Resultados: foram notificados 4.710 casos com SRAG; 53,4% foram SRAG relacionados à COVID-19 em 2020 e, 87,5%, em 2021 (p<0,001). Comparando os anos 2020 e 2021, o perfil sociodemográfico modificou quanto faixa etária, cor da pele e escolaridade (p<0,001). Quanto aos aspectos clínicos, houve redução da prevalência de condições de saúde preexistente, exceto obesidade, alterações nos sinais e sintomas relatados e diminuição de internações hospitalares e na Unidade de Terapia Intensiva. Conclusão: as mudanças no perfil podem refletir o efeito das diferentes variantes e o início da imunização para SARS-CoV-2.(AU)

Justificación y objetivos: comparar los aspectos clínicos y sociodemográficos de individuos con SARS notificados en el interior de Rio Grande do Sul en los años 2020 y 2021. Métodos: estudio descriptivo transversal, realizado de marzo de 2020 a octubre de 2021. Se analizaron variables clínicas y sociodemográficas de individuos con síntomas de SARS, comparadas mediante análisis descriptivos univariados, según el año de notificación. Resultados: se notificaron 4.710 casos de SARS; el 53,4% fueron SARS relacionados con COVID-19 en 2020 y el 87,5% en 2021 (p<0,001). Comparando los años 2020 y 2021, el perfil sociodemográfico cambió en cuanto a grupo de edad, color de piel y escolaridad (p<0,001). En cuanto a los aspectos clínicos, hubo reducción en la prevalencia de condiciones de salud preexistentes, excepto obesidad, cambios en los signos y síntomas reportados y reducción en los ingresos hospitalarios y en la Unidad de Cuidados Intensivos. Conclusión: los cambios en el perfil pueden reflejar el efecto de las diferentes variantes y el inicio de la inmunización para el SARS-CoV-2.(AU)

Mpox: Aspectos epidemiológicos, imunopatogênicos e manejo pré e pós-infecção / Mpox: Epidemiological, immunopathogenic aspects and pre- and post-infection management

Mpoxou Varíola M é uma zoonose causada por vírus do gênero Orthopoxvirus, causadores também da varíola comum. É uma doença considerada rara e autolimitada, sendo endêmica em países africanos. Entretanto, no ano de 2022 ganhou destaque devido ao surto global que se iniciou, quando o mundo ainda se recuperava da pandemia da COVID-19. Dessa forma, por se tratar de uma doença emergente, a presente revisão visa pontuar aspectos gerais do que se sabe até o momento sobre a Mpox, desde sua imunopatogenia até as formas atuais de prevenção e cuidados pós-infecção

Mpox or Variola M is a zoonosis caused by viruses of the genus Orthopoxvirus, which also cause smallpox. It is a disease considered rare and self-limiting, being endemic in African countries. However, in 2022, it gained prominence due to the global outbreak that began when the world was still recovering from the COVID-19 pandemic. Thus, as it is an emerging disease, this review aims to point out general aspects of what is known so far about Mpox, from its immunopathogenesis to current forms of prevention and post-infection care

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

[Predictive value of postoperative serum procalcitonin concentration for moderate to severe acute respiratory distress syndrome in patients undergoing cardiopulmonary bypass surgery].

OBJECTIVE: To explore the changes of serum procalcitonin (PCT) level in patients with moderate and severe acute respiratory distress syndrome (ARDS) after cardiac surgery under cardiopulmonary bypass (CPB), and try to find out the best cut-off of PCT to predict the progression to moderate and severe ARDS. METHODS: Medical records of patients undergoing cardiac surgery with CPB in Fujian Provincial Hospital from January 2017 to December 2019 were retrospectively analyzed. Adult patients who were admitted in intensive care unit (ICU) for more than 1 day and had PCT values on the first postoperative day were enrolled. Clinical data such as patient demographics, past history, diagnosis, and New York Heart Association (HYHA) classification, and the operation mode, procedure duration, CPB duration, aortic clamp duration, intraoperative fluid balance, calculation of 24 hours postoperative fluid balance and vasoactive-inotropic score (VIS); 24 hours postoperative C-reactive protein (CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP) and PCT levels were collected. Two clinicians independently made the diagnosis of ARDS according to the Berlin definition, and the diagnosis was established only in patients with a consistent diagnosis. The differences in each parameter were compared between patients with moderate to severe ARDS and those without or with mild ARDS. Analysis of the ability of PCT to predict moderate to severe ARDS was evaluated by receiver operator characteristic curve (ROC curve). Multivariate Logistic regression was conducted to determine the risk factors of the development of moderate to severe ARDS. RESULTS: 108 patients were finally enrolled, including 37 patients with mild ARDS (34.3%), 35 patients with moderate ARDS (32.4%), 2 patients with severe ARDS (1.9%), and 34 patients without ARDS. Compared with patients with no or mild ARDS, patients with moderate to severe ARDS were older (years old: 58.5±11.1 vs. 52.8±14.8, P < 0.05), with a higher proportion of combined hypertension [45.9% (17/37) vs. 25.4% (18/71), P < 0.05], longer operative time (minutes: 363.2±120.6 vs. 313.5±97.6, P < 0.05), and higher mortality (8.1% vs. 0, P < 0.05), but there were no differences in the VIS score, incidence of acute renal failure (ARF), CPB duration, aortic clamp duration, and intraoperative bleeding, transfusion volume, and fluid balance between the two groups. Serum PCT and NT-proBNP levels in patients with moderate to severe ARDS at postoperative day 1 were significantly higher than those in patients with no or mild ARDS [PCT (µg/L): 16.33 (6.96, 32.56) vs. 2.21 (0.80, 5.76), NT-proBNP (ng/L): 2 405.0 (1 543.0, 6 456.5) vs. 1 680.0 (1 388.0, 4 667.0), both P < 0.05]. ROC curve analysis showed that the area under the curve (AUC) for PCT to predict the occurrence of moderate to severe ARDS was 0.827 [95% confidence interval (95%CI) was 0.739-0.915, P < 0.05]. When PCT cut-off value was 7.165 µg/L, the sensitivity was 75.7% and the specificity was 84.5%, for differentiating patients who developed moderate to severe ARDS from who did not. Multivariate Logistic regression showed that age and the elevated PCT concentration were independent risk factors for the development of moderate to severe ARDS [age: odds ratio (OR) = 1.105, 95%CI was 1.037-1.177, P = 0.002; PCT: OR = 48.286, 95%CI was 10.282-226.753, P < 0.001]. CONCLUSIONS: Patients with moderate to severe ARDS undergoing CPB cardiac surgery have a higher serum concentration of PCT than patients with no or mild ARDS. Serum PCT level may be a promising biomarker to predict the development of moderate to severe ARDS, the cut-off value is 7.165 µg/L.

Perfil de casos e óbitos confirmados de síndrome respiratória aguda grave por covid-19 no interior da Bahia / Profile of confirmed cases and deaths of severe acute respiratory syndrome by COVID-19 in the interior of Bahia / Perfil de casos y muertes confirmadas por síndrome respiratorio agudo grave por COVID-19 en el interior de Bahía

A síndrome respiratória aguda grave (SRAG) pode ser causada pelo SARS-CoV-2, doença infectocontagiosa que afeta os pulmões, reconhecida como ameaça global e com morbimortalidade significativa. O objetivo deste estudo foi analisar o perfil epidemiológico de casos e óbitos confirmados por síndrome respiratória aguda grave por covid-19 em Juazeiro, município da Bahia, entre os meses de janeiro e dezembro de 2020. Trata-se de um estudo transversal que utilizou dados secundários dos casos notificados no Sistema de Informação da Vigilância Epidemiológica da Gripe (Sivep-Gripe) por residência. Os dados foram coletados em junho de 2021 e analisados por meio de estatística descritiva e inferencial. Os resultados apontaram 16.760 casos suspeitos de covid-19, 6.180 casos confirmados através de testes laboratoriais, e, entre os casos confirmados, 142 faleceram. A maioria dos óbitos por covid-19 foi de homens, idosos e pardos, com sintomatologia de coriza, dispneia, tosse, febre e outros sintomas. As comorbidades analisadas estavam mais presentes em mulheres, contudo, essa característica frequentemente é observada em homens. Condições como doenças cardíacas crônicas, diabetes, doenças renais em estágio avançado e obesidade predominaram em pessoas pardas que faleceram por conta da covid-19. Compreender as características dos casos de covid-19 pode fornecer subsídios para profissionais da saúde e gestores desenvolverem estratégias principalmente voltadas à prevenção de complicações e óbitos relacionados à doença.

Severe acute respiratory syndrome (SARS) can be caused by SARS-CoV-2, an infectious disease that affects the lungs, recognized as a global threat and with significant morbidity and mortality. The aim of this study was to analyze the epidemiological profile of confirmed cases and deaths of severe acute respiratory syndrome caused by COVID-19 in Juazeiro, municipality from Bahia, between January and December 2020. It is a cross-sectional study that used secondary data from cases reported in the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) by household. Data were collected in June 2021 and analyzed using descriptive and inferential statistics. Results indicated 16,760 suspected cases of COVID-19 with 6,180 cases confirmed by laboratory tests, and, of the confirmed cases, 142 died. Most deaths from COVID-19 were of male, older, and mixed race people, with symptoms of coryza, dyspnea, cough, fever, and other symptoms. The analyzed comorbidities were more present in women; however, this characteristic is often observed in men. Conditions such as chronic heart disease, diabetes, advanced kidney disease, and obesity predominated in mixed race people who died from COVID-19. Understanding these characteristics of the COVID-19 cases can provide subsidies for health professionals and managers to develop strategies mainly aimed at preventing complications and deaths related to the disease.

El síndrome respiratorio agudo grave (SRAS) es probablemente causado por el SARS-CoV-2, una enfermedad infecciosa que afecta los pulmones considerada una amenaza global, con significativa morbimortalidad. El objetivo de este estudio fue analizar el perfil epidemiológico de los casos positivados y de las muertes por síndrome respiratorio agudo grave causado por la covid-19 en Juazeiro, municipio de Bahía (Brasil), en el período entre enero y diciembre de 2020. Se trató de un estudio transversal, que utilizó datos secundarios de casos notificados en el Sistema de Información de Vigilancia Epidemiológica de Influenza (SIVEP-Gripe) por hogar. Los datos se recopilaron en junio de 2021 y se analizaron mediante estadística descriptiva e inferencial. Los resultados arrojaron 16.760 casos sospechosos de la covid-19, con 6.180 casos confirmados mediante pruebas de laboratorio; de los cuales 142 fallecieron. La mayoría de los pacientes que fallecieron por covid-19 eran del sexo masculino, de edad avanzada, pardos, con síntomas de coriza, disnea, tos, fiebre y otros síntomas. Las comorbilidades analizadas estuvieron más presentes en mujeres, sin embargo, esta característica se observa con frecuencia en hombres. Las condiciones como cardiopatía crónica, diabetes, enfermedad renal avanzada y obesidad predominaron en pardos que fallecieron por la covid-19. La comprensión de estas características puede proporcionar subsidios para que los profesionales y gestores de la salud desarrollen estrategias dirigidas principalmente a la prevención de complicaciones y muertes relacionadas con la enfermedad.

A people-centered decentralized outreach model toward HCV micro-elimination in hyperendemic areas: COMPACT study in SARS Co-V2 pandemic.

OBJECTIVES: Gaps in linkage-to-care remain the barriers toward hepatitis C virus (HCV) elimination in the directly-acting-antivirals (DAA) era, especially during SARS Co-V2 pandemics. We established an outreach project to target HCV micro-elimination in HCV-hyperendemic villages. METHODS: The COMPACT provided "door-by-door" screening by an "outreach HCV-checkpoint team" and an "outreach HCV-care team" for HCV diagnosis, assessment and DAA therapy in Chidong/Chikan villages between 2019 and 2021. Participants from neighboring villages served as Control group. RESULTS: A total of 5731 adult residents participated in the project. Anti-HCV prevalence rate was 24.0% (886/3684) in Target Group and 9.5% (194/2047) in Control group (P < 0.001). The HCV-viremic rates among anti-HCV-positive subjects were 42.7% and 41.2%, respectively, in Target and Control groups. After COMPACT engagement, 80.4% (304/378) HCV-viremic subjects in the Target group were successfully linked-to-care, and Control group (70% (56/80), P = 0.039). The rates of link-to-treatment and SVR12 were comparable between Target (100% and 97.4%, respectively) and Control (100% and 96.4%) groups. The community effectiveness was 76.4% in the COMPACT campaign, significantly higher in Target group than in Control group (78.3% versus 67.5%, P = 0.039). The community effectiveness decreased significantly during SARS Co-V2 pandemic in Control group (from 81% to 31.8%, P < 0.001), but not in Target group (80.3% vs. 71.6%, P = 0.104). CONCLUSIONS: The outreach door-by-door screen strategy with decentralized onsite treatment programs greatly improved HCV care cascade in HCV-hyperendemic areas, a model for HCV elimination in high-risk marginalized communities in SARS Co-V2 pandemic.

Enhanced stability of the SARS CoV-2 spike glycoprotein following modification of an alanine cavity in the protein core.

The spike (S) glycoprotein of SARS CoV-2 is the target of neutralizing antibodies (NAbs) that are crucial for vaccine effectiveness. The S1 subunit binds ACE2 while the S2 subunit mediates virus-cell membrane fusion. S2 is a class I fusion glycoprotein subunit and contains a central coiled coil that acts as a scaffold for the conformational changes associated with fusion function. The coiled coil of S2 is unusual in that the 3-4 repeat of inward-facing positions are mostly occupied by polar residues that mediate few inter-helical contacts in the prefusion trimer. We examined how insertion of bulkier hydrophobic residues (Val, Leu, Ile, Phe) to fill a cavity next to Ala1016 and Ala1020 in the 3-4 repeat affects the stability and antigenicity of S trimers. Substitution of Ala1016 with bulkier hydrophobic residues in the context of a prefusion-stabilized S trimer, S2P-FHA, was associated with increased thermal stability. S glycoprotein membrane fusion function was retained with Ala1016/Ala1020 cavity-filling mutations associated with improved recombinant S2P-FHA thermostability, however 2 mutants, A1016L and A1016V/A1020I, lacked ability to mediate entry of S-HIV-1 pseudoparticles into 293-ACE2 cells. When assessed as immunogens, two thermostable S2P-FHA mutants derived from the ancestral isolate, A1016L (16L) and A1016V/A1020I (VI) elicited neutralizing antibody with 50%-inhibitory dilutions (ID50s) in the range 2,700-5,110 for ancestral and Delta-derived viruses, and 210-1,744 for Omicron BA.1. The antigens elicited antibody specificities directed to the receptor-binding domain (RBD), N-terminal domain (NTD), fusion peptide and stem region of S2. The VI mutation enabled the production of intrinsically stable Omicron BA.1 and Omicron BA.4/5 S2P-FHA-like ectodomain oligomers in the absence of an external trimerization motif (T4 foldon), thus representing an alternative approach for stabilizing oligomeric S glycoprotein vaccines.

Rinovirus en pandemia. Ciudad de Santa Fe, Argentina. Bienio 2020-2021 / Rhinovirus in pandemic. Santa Fe city, Argentina. Biennium 2020-2021

En el contexto de la pandemia de COVID-19, a partir de 2020, la Unidad Centinela de Enfermedades Tipo Influenza (UC-ETI) (Santa Fe, Argentina) integró la vigilancia clínica y por laboratorio de SARS-CoV-2 y rinovirus (HRV) a la habitual vigilancia de influenza y otros virus respiratorios (OVR). El objetivo de este estudio transversal y retrospectivo fue describir las características clínico-epidemiológicas de casos de ETI de la ciudad de Santa Fe, con diagnóstico de HRV confirmado durante 2020-2021, en el marco de la UC-ETI. Del total de 600 casos de ETI cuyas muestras fueron analizadas, más del 50,0% fueron mujeres; y la mayor proporción se concentró en el grupo de 15 a 39 años (40,2%). El 33,7% registró al menos una comorbilidad o factor de riesgo, siendo la hipertensión arterial, asma, diabetes, obesidad y EPOC las más frecuentes. Además de fiebre y tos, los signos/síntomas predominantes fueron odinofagia, mialgia y cefalea. El porcentaje de positividad fue de 41,3% en 2020, 27,8% en 2021 y 35,5% en 2020-2021. De las muestras positivas del bienio (213), 59,0% fue SARS-CoV-2, 40,0% HRV y 1,0% OVR. La mayor proporción de diagnósticos positivos de SARS-CoV-2 se concentró en pacientes de 15 años y más, y la de HRV en menores de 15. Los periodos en los que predominó la circulación de HRV no lo hizo la de SARS-CoV-2, y viceversa. El aporte a la carga real de las infecciones virales respiratorias y su impacto en la salud pública destaca la importancia de sostener la vigilancia de HRV

In the context of the COVID-19 pandemic, in 2020, the influenza-like illness Sentinel Unit (ILI-SU) (Santa Fe, Argentina), integrated clinical and laboratory surveillance of SARS-CoV-2 and Rhinovirus (HRV) to the usual surveillance of Influenza and other respiratory viruses (ORV). The objective of this cross-sectional and retrospective study was to describe the clinical-epidemiological characteristics of ILI cases of Santa Fe city, who had a confirmed HRV diagnosis during 2020-2021, by the ILI-SU. Of a total of 600 ILI cases whose samples were analyzed, more than 50.0% were women; and the highest proportion was concentrated in the group between 15 and 39 years of age (40.2%). 33.7% of the cases registered at least one comorbidity or risk factor, among which arterial hypertension, asthma, diabetes, obesity and COPD were the most frequent. In addition to fever and cough, the predominant signs/symptoms were sore throat, myalgia and headache. The percentage of positivity was 41.3% in 2020, 27.8% in 2021, and 35.5% in 2020-2021. Of the biennium positive samples (213), 59.0% were SARS-CoV-2, 40.0% HRV, and 1.0% ORV. The highest proportion of SARS-CoV-2 positive diagnoses were concentrated in patients 15 years of age and older, while the highest proportion of HRV positive diagnoses were concentrated in patients under 15 years of age. The periods in which the circulation of HRV predominated did not predominated SARS-CoV-2, and vice versa. The contribution to the real burden of respiratory viral infections and its impact on public health, highlight the importance of sustaining HRV surveillance