Humoral immune response in people living with HIV after administration of SARS-CoV-2 vaccine CoronaVac or BNT162b2 or CoronaVac/BNT162b2 booster sequence: A cross-sectional study.

BACKGROUND: The evidence of SARS-CoV-2 vaccine effectiveness in people living with HIV (PLWH) is limited. This study evaluated the humoral immune response to CoronaVac™ (virus inactivated) and BNT162b2 (mRNA- based) vaccines in PLWH and HIV-negative controls, with and without a booster sequence. METHODS: We conducted a cross-sectional study on PLWH and HIV-negative controls who received CoronaVac or BNT162b2, with a subgroup receiving a CoronaVac/BNT162b2 booster. Blood samples were collected 4-6 months after primary vaccination and tested for anti-SARS-CoV-2 protein S (aSAb) and neutralizing antibodies (NtAb) using validated assays. Immune response was evaluated by age, sex, previous COVID-19 history, and CD4 + cell count. FINDINGS: One hundred and eighty nine participants were enrolled with 161 (85%) being PLWH. Among participants without previous known COVID-19, median aSAb levels were significantly lower in PLWH who received CoronaVac compared to BNT162b2 (32 U/mL vs. 587 U/mL, p < 0.001), with similar results in HIV-negative controls. NtAb presence was also significantly lower after CoronaVac compared to BNT162b2 (30% vs. 93%, p < 0.001). The booster sequence group showed a significant increase in aSAb titers in both PLWH and HIV-negative controls (from 33 U/ml to 2500 U/ml, p < 0.001), and NtAb positivity increased from 20% to 95 % in PLWH, and 27% to 100% in HIV-negative controls. Prior COVID-19 led to significantly higher post-vaccine antibody titers particularly in the BNT162b2 group. PLWH with CD4 + count < 200 cells/mL showed a weaker immune response to both vaccines. INTERPRETATION: CoronaVac resulted in a weaker immune response in both PLWH and HIV-negative controls compared to BNT162b2, particularly in immunosuppressed PLWH without prior COVID-19. Hybrid immunity and heterologous booster vaccination increased antibody levels. FUNDING: Local funding.

Post-COVID-19 condition: a sex-based analysis of clinical and laboratory trends.

Background and aim: Post-COVID-19 condition (PCC) encompasses long-lasting symptoms in individuals with COVID-19 and is estimated to affect between 31-67% of patients, with women being more commonly affected. No definitive biomarkers have emerged in the acute stage that can help predict the onset of PCC, therefore we aimed at describing sex-disaggregated data of PCC patients from a local cohort and explore potential acute predictors of PCC and neurologic PCC. Methods: A local cohort of consecutive patients admitted with COVID-19 diagnosis between June 2020 and July 2021 were registered, and clinical and laboratory data were recorded. Only those <65 years, discharged alive and followed up at 6 and 12 months after admission were considered in these analyses. Multivariable logistic regression analysis was performed to explore variables associated with PCC (STATA v 18.0). Results: From 130 patients in the cohort, 104 were contacted: 30% were women, median age of 42 years. At 6 months, 71 (68%) reported PCC symptoms. Women exhibited a higher prevalence of any PCC symptom (87 vs. 60%, p = 0.007), lower ferritin (p = 0.001) and procalcitonin (p = 0.021) and higher TNF levels (p = 0.042) in the acute phase compared to men. Being women was independently associated to 7.60 (95% CI 1.27-45.18, p = 0.026) higher risk for PCC. Moreover, women had lower return to normal activities 6 and 12 months. Conclusion: Our findings highlight the lasting impact of COVID-19, particularly in young women, emphasising the need for tailored post-COVID care. The lower ferritin levels in women are an intriguing observation, warranting further research. The study argues for comprehensive strategies that address sex-specific challenges in recovery from COVID-19.

Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study.

BACKGROUND: Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. METHODS: In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. FINDINGS: ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). INTERPRETATION: ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. FUNDING: National Institutes of Health and Agencia de Investigación y Desarrollo. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Chromosomal microarrays testing in children with developmental disabilities and congenital anomalies / Análise cromossômica por microarray em crianças com deficiências de desenvolvimento e anomalias congênitas

OBJECTIVES: Clinical use of microarray-based techniques for the analysis of many developmental disorders has emerged during the last decade. Thus, chromosomal microarray has been positioned as a first-tier test. This study reports the first experience in a Chilean cohort. METHODS: Chilean patients with developmental disabilities and congenital anomalies were studied with a high-density microarray (CytoScan(tm) HD Array, Affymetrix, Inc., Santa Clara, CA, USA). Patients had previous cytogenetic studies with either a normal result or a poorly characterized anomaly. RESULTS: This study tested 40 patients selected by two or more criteria, including: major congenital anomalies, facial dysmorphism, developmental delay, and intellectual disability. Copy number variants (CNVs) were found in 72.5% of patients, while a pathogenic CNV was found in 25% of patients and a CNV of uncertain clinical significance was found in 2.5% of patients. CONCLUSION: Chromosomal microarray analysis is a useful and powerful tool for diagnosis of developmental diseases, by allowing accurate diagnosis, improving the diagnosis rate, and discovering new etiologies. The higher cost is a limitation for widespread use in this setting. .

OBJETIVO: O uso clínico de técnicas baseadas em microarrays para a análise de transtornos de desenvolvimento tem surgido durante a última década. Assim, o microarray cromossômico tem sido posicionado como um teste de primeiro nível clínico. Relatamos a primeira experiência em uma coorte chilena. MÉTODOS: Pacientes chilenos com atraso de desenvolvimento e anomalias congênitas foram estudados com um microarray de alta densidade (CytoScan(tm) HD Array, Affymetrix, Inc., Santa Clara, CA, EUA). Pacientes tiveram estudos citogenéticos anteriores, ou um resultado normal ou de uma anomalia não bem caracterizada. RESULTADOS: Foram analisados 40 pacientes selecionados por dois ou mais critérios, incluindo: anomalias congênitas maiores, dismorfismo facial, atraso de desenvolvimento e deficiência intelectual. Uma variante do número de cópia (CNV) foi encontrada em 72,5% dos pacientes, enquanto que uma CNV patogênica foi encontrada em 25% dos pacientes e uma CNV de significado clínico incerto foi encontrada em 2,5% dos pacientes. CONCLUSÕES: A análise cromossômica microarray é uma ferramenta útil e poderosa em transtornos de desenvolvimento, permite um diagnóstico preciso, melhora a taxa de diagnóstico e descobre novas etiologias. O custo mais elevado é uma limitação para um uso difundido em nossa realidade. .

Diagnóstico de intolerancia a la lactosa en adultos: rendimiento comparativo de la clínica, test de hidrógeno espirado y test genético / Comparative performance of symptoms questionnaire, hydrogen test and genetic test for lactose intolerance

Background: Genetically programmed adult-type hypolactasia affects 56% of Chilean population. Ideally, diagnosis should be confirmed. Aim: To compare diagnostic yield of genetic test, hydrogen (H2) expiratory test and a validated symptomatic structured survey (SS). Material and Methods: Patients submitted to H2 test answered a historic (anamnestic) and current SS (after the ingestion of 25 g of lactose). A blood sample was obtained for determination of genetic polymorphisms C/T_13910, C/G_13907 and G/A_22018 by polymerase chain reaction. The gold standard for diagnosis of lactose intolerance (LI) was the agreement of at least two of three tests. Results: Sixty-one participants aged 39 ± 12 years (21 males), were studied. Anamnestic SS was diagnostic of LI in all cases (score > 7), while current SS detected LI in 27/61 (46%). H2 test (an increase > 15 ppm after ingestion of 25 g of lactose) showed LI in 31/61 (51%). The locus C/G_13907 showed no polymorphism and locus G/A_22018 was in complete linkage disequilibrium with C/T_13910. Genotype C/C_13910, associated to hypolactasia, was present in 30/58 (52%). According to the gold-standard, 32/61 (52.5%) patients were diagnosed as LI. Sensitivity and specificity were, respectively, 79% and 69% for current SS, 93% and 93% for H2 test and 97% and 93% for the genetic test. The last two showed a positive likelihood ratio (LR) > 10 and a negative LR < 0.1, figures within the range considered clinically useful. Conclusions: Genotype C/C_13910 is responsible for hypolactasia in this population. Anamnestic report of symptoms after milk ingestion and symptoms after lactose ingestion, are not accurate enough. H2 and genetic tests are simple and similarly accurate to diagnose lactose intolerance in adults.