Lung directed antibody gene transfer confers protection against SARS-CoV-2 infection.

BACKGROUND: The COVID-19 pandemic continues to be a worldwide threat and effective antiviral drugs and vaccines are being developed in a joint global effort. However, some elderly and immune-compromised populations are unable to raise an effective immune response against traditional vaccines. AIMS: We hypothesised that passive immunity engineered by the in vivo expression of anti-SARS-CoV-2 monoclonal antibodies (mAbs), an approach termed vectored-immunoprophylaxis (VIP), could offer sustained protection against COVID-19 in all populations irrespective of their immune status or age. METHODS: We developed three key reagents to evaluate VIP for SARS-CoV-2: (i) we engineered standard laboratory mice to express human ACE2 via rAAV9 in vivo gene transfer, to allow in vivo assessment of SARS-CoV-2 infection, (ii) to simplify in vivo challenge studies, we generated SARS-CoV-2 Spike protein pseudotyped lentiviral vectors as a simple mimic of authentic SARS-CoV-2 that could be used under standard laboratory containment conditions and (iii) we developed in vivo gene transfer vectors to express anti-SARS-CoV-2 mAbs. CONCLUSIONS: A single intranasal dose of rAAV9 or rSIV.F/HN vectors expressing anti-SARS-CoV-2 mAbs significantly reduced SARS-CoV-2 mimic infection in the lower respiratory tract of hACE2-expressing mice. If translated, the VIP approach could potentially offer a highly effective, long-term protection against COVID-19 for highly vulnerable populations; especially immune-deficient/senescent individuals, who fail to respond to conventional SARS-CoV-2 vaccines. The in vivo expression of multiple anti-SARS-CoV-2 mAbs could enhance protection and prevent rapid mutational escape.

Proposal for Human Respiratory Syncytial Virus Nomenclature below the Species Level.

Human respiratory syncytial virus (HRSV) is the leading viral cause of serious pediatric respiratory disease, and lifelong reinfections are common. Its 2 major subgroups, A and B, exhibit some antigenic variability, enabling HRSV to circulate annually. Globally, research has increased the number of HRSV genomic sequences available. To ensure accurate molecular epidemiology analyses, we propose a uniform nomenclature for HRSV-positive samples and isolates, and HRSV sequences, namely: HRSV/subgroup identifier/geographic identifier/unique sequence identifier/year of sampling. We also propose a template for submitting associated metadata. Universal nomenclature would help researchers retrieve and analyze sequence data to better understand the evolution of this virus.

Transposon-mediated generation of CAR-T cells shows efficient anti B-cell leukemia response after ex vivo expansion.

CAR-T-cell therapy has shown considerable advance in recent years, being approved by regulatory agencies in US, Europe, and Japan for the treatment of refractory patients with CD19+ B-cell leukemia or diffuse large B-cell lymphoma. Current methods for CAR-T-cell production use viral vectors for T-cell genetic modification and can take up to 15 days to generate the infusion product. The development of simple and less costly manufacturing protocols is needed in order to meet the increasing demand for this therapy. In this present work, we generated 19BBz CAR-T cells in 8 days using a protocol based on the non-viral transposon-based vector Sleeping Beauty. The expanded cells display mostly a central memory phenotype, expressing higher levels of inhibitory receptors when compared with mock cells. In addition, CAR-T cells were cytotoxic against CD19+ leukemia cells in vitro and improved overall survival rates of mice xenografted with human RS4;11 or Nalm-6 B-cell leukemias. Infused CAR-T cells persisted for up to 28 days, showing that they are capable of long-term persistence and antitumor response. Altogether, these results demonstrate the effectiveness of our protocol and pave the way for a broader application of CAR-T-cell therapy.

Dengue Virus 1 Outbreak in Buenos Aires, Argentina, 2016.

The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Phylogenetic, phylodynamic, and phylogeographic analyses of 82 samples from dengue patients revealed co-circulation of 2 genotype V dengue virus lineages, suggesting that this virus has become endemic to the Buenos Aires metropolitan area.

What about adolescents' mental health after the pandemics? An analyses of a grade II hospital.

OBJECTIVES: Suicidal ideation and suicide are serious situations that affect children and adolescents. The restrictions imposed by the SARS-CoV-2 pandemic have had a significant negative impact, due to social isolation, prolonged screen exposure and reduced outdoor activities. This study aims to compare the access to the Pediatric Emergency Department due to suicidal ideation and suicide attempts before and during the pandemic. METHODS: This descriptive and retrospective study analyzed clinical records of children/adolescents who attended a Level II Pediatric Emergency Department of a hospital due to suicidal ideation and/or suicide attempts, between March 2018 and March 2020 (pre-pandemic period) and April 2020 to March 2022 (pandemic period). Demographic (age and sex) and clinical (psychopharmacological therapy, discharge destination and follow-up psychiatric/psychological consultations) variables were collected. Statistical analysis was performed using Microsoft Excel 2022® and SPSS v20.0®, considering statistical significance at p<0.05. RESULTS: A total of 71 children/adolescents were admitted for suicidal ideation, with a median age of 15 years (minimum: 10 years, maximum: 17 years), 27 in pre-pandemic period and 44 in pandemic period (p<0.001). The majority were girls, with a significant increase in pandemic period (pre-pandemic: 55.6 %, pandemic: 79.6 %; p<0.05). The age group with the highest increase in admissions was 15 years. There was a significant increase in suicidal attempts among girls (p<0.05) as well as self-harm behaviors (p<0.01). There was also a significant increase in the number of psychology/child psychiatry follow-up consultations in pandemic period (p<0.05). Most patients were referred to another hospital in both periods (pre-pandemic: 55.6 %, pandemic: 68.2 %) at discharge. CONCLUSIONS: During the pandemic period, there was an increase in the number of suicidal ideation cases, particularly among females, as well as in suicide attempts cases, which appears to be correlated with the pandemic restrictions. Larger-scale studies are needed to draw more accurate conclusions.

An Outbreak of SARS-CoV-2 in Captive Armadillos Associated with Gamma Variant in Argentina.

The current pandemic produced by SARS-CoV-2 and its variants represent an example of the one health concept in which humans and animals are components of the same epidemiologic chain. Animal reservoirs of these viruses are thus the focus of surveillance programs, to monitor their circulation and evolution in potentially new hosts and reservoirs. In this work, we report the detection of the SARS-CoV-2 Gamma variant infection in four specimens of Chaetophractus villosus (big hairy armadillo/armadillo peludo) in Argentina. In addition to the finding of a new wildlife species susceptible to SARS-CoV-2 infection, the identification of the Gamma variant three months after its last detection in humans in Argentina is a noteworthy result, which can be due to alternative non-exclusive scenarios, such as unidentified viral reservoirs, unrecognized circulation in humans or species-specific variation in incubation periods.

Buried Penis: A Rare Cause of Lower Urinary Tract Symptoms in the Pediatric Population.

A buried penis is a probably underdiagnosed entity. It is defined as a penis of normal size that appears to be smaller than expected due to concealment within the pubic tissue. This case report explores the presentation of a 12-month-old male infant with exuberant ballooning of the prepuce during micturition, requiring manual expression of urine for the duration of two months prior to presentation. The penis was not visible above the skin level, with only the glands covered by prepuce protruding. However, the penis could be exposed when holding the base of the penis, revealing a regular-sized penis. The clinical diagnosis of a buried penis with megaprepuce was assumed, and the patient was referred to the pediatric surgery department for further management. Corrective surgery was performed nine months later with excellent cosmetic and functional results. The buried penis has a typical appearance with a partially visible or completely invisible penis, with only the glans covered by prepuce protruding, and it can be completely asymptomatic or cause micturition difficulties, sexual dysfunction, and recurrent urinary tract infections or balanitis. The diagnosis is clinical and the treatment is surgical, although the surgical approach is controversial.

Importance of Genetic Diagnosis in Global Developmental Delay: A Case of Cabezas Syndrome Caused by CUL4B Gene Deletion and Not Identified by Array-CHG.

Global developmental delay (GDD) and intellectual disability (ID) are common reasons for referral to neurodevelopmental assessment. The etiology of GDD and ID can be genetic, acquired, or multifactorial. We report a case of a 10-year-old boy with ID and GDD who was diagnosed with Cabezas syndrome, a rare genetic disorder caused by a deletion of the CUL4B gene. Despite normal results from previous testing, exome sequencing with copy number variation analysis led to the identification of the deletion. Early diagnosis of GDD and ID is crucial for effective patient management, including planning interventions and providing support, therapy, and genetic counseling for families.

Evolutionary dynamics of respiratory syncytial virus in Buenos Aires: Viral diversity, migration, and subgroup replacement.

Globally, the human respiratory syncytial virus (RSV) is one of the major causes of lower respiratory tract infections (LRTIs) in children. The scarcity of complete genome data limits our understanding of RSV spatiotemporal distribution, evolution, and viral variant emergence. Nasopharyngeal samples collected from hospitalized pediatric patients from Buenos Aires tested positive for RSV LRTI during four consecutive outbreaks (2014-2017) were randomly subsampled for RSV complete genome sequencing. Phylodynamic studies and viral population characterization of genomic variability, diversity, and migration of viruses to and from Argentina during the study period were performed. Our sequencing effort resulted in one of the largest collections of RSV genomes from a given location (141 RSV-A and 135 RSV-B) published so far. RSV-B was dominant during the 2014-2016 outbreaks (60 per cent of cases) but was abruptly replaced by RSV-A in 2017, with RSV-A accounting for 90 per cent of sequenced samples. A significant decrease in RSV genomic diversity-represented by both a reduction in genetic lineages detected and the predominance of viral variants defined by signature amino acids-was observed in Buenos Aires in 2016, the year prior to the RSV subgroup predominance replacement. Multiple introductions to Buenos Aires were detected, some with persistent detection over seasons, and also, RSV was observed to migrate from Buenos Aires to other countries. Our results suggest that the decrease in viral diversity may have allowed the dramatic predominance switch from RSV-B to RSV-A in 2017. The immune pressure generated against circulating viruses with limited diversity during a given outbreak may have created a fertile ground for an antigenically divergent RSV variant to be introduced and successfully spread in the subsequent outbreak. Overall, our RSV genomic analysis of intra- and inter-outbreak diversity provides an opportunity to better understand the epochal evolutionary dynamics of RSV.

Shedding of infectious SARS-CoV-2 in two asymptomatic children.

Asymptomatic infections with SARS-CoV-2 are associated with viral transmission and have a key role in the propagation of the pandemic. Understanding viral shedding during asymptomatic infections is critical. Unfortunately, data on asymptomatic SARS-CoV-2 infection in children is extremely limited. To determine the presence of viral viable shedding, we prospectively followed two healthy children of a family where both parents developed mild COVID-19 (April 2021). SARS-CoV-2 detection was made by RT-PCR and virus isolation by cell culture from saliva samples. Positive samples were sequenced to identify variants of SARS-CoV-2. Serum samples were evaluated to determine the presence of antibodies using a single enzyme-linked immunosorbent assay (ELISA, COVIDAR IgG). Both children were SARS-CoV-2 positive and asymptomatic. In addition, the virus grew in cell culture from saliva samples. Furthermore, one child showed viable SARS-CoV-2 for at least 17 days after the onset symptoms from his father. The recommended isolation period for asymptomatic contacts during the acquisition of data had been established for 10 days; however, this child remained with viable virus beyond that period. The positive samples from both children were consistent with B.1.1.28.1 lineage (Gamma). In both asymptomatic children, anti-Spike IgG was detected. Asymptomatic children may represent a source of infection that should not be underestimated during this pandemic.

Las infecciones asintomáticas por SARS-CoV-2 están asociadas a la transmisión viral y tienen un papel clave en la propagación de la pandemia. Comprender la excreción viral durante las infecciones asintomáticas es fundamental. Desafortunadamente, los datos sobre la infección asintomática por SARS-CoV-2 en niños son extremadamente limitados. Para determinar la presencia de excreción de virus viable, se siguió prospectivamente a dos niños sanos de una familia en la que ambos padres desarrollaron COVID-19 leve (abril 2021). La detección de SARS-CoV-2 se realizó por RT-PCR y el aislamiento del virus por cultivo celular a partir de muestras de saliva. Las muestras positivas se secuenciaron para identificar variantes de SARS-CoV-2. En las muestras de suero se determinó la presencia de anticuerpos utilizando un ensayo de ELISA (COVIDAR IgG). Ambos niños fueron positivos para SARS-CoV-2 y asintomáticos. Además, el virus creció en cultivos celulares a partir de muestras de saliva. Uno de los niños mantuvo SARS-CoV-2 viables durante al menos 17 días después de la aparición de los síntomas de su padre. El período de aislamiento recomendado para contactos asintomáticos durante la adquisición de datos se había establecido en 10 días, sin embargo, este niño permaneció con virus viable más allá de ese período. Las muestras positivas de estos niños correspondieron al linaje B.1.1.28.1 (Gamma). En ambos niños asintomáticos se detectó anticuerpos IgG anti-Spike. Concluimos que los niños asintomáticos pueden representar una fuente de infección que no debe subestimarse durante esta pandemia.

The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2.

New antiviral treatments are needed to deal with the unpredictable emergence of viruses. Furthermore, vaccines and antivirals are only available for just a few viral infections, and antiviral drug resistance is an increasing concern. Cyanidin (a natural product also called A18), a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, through its anti-inflammatory effects. Regarding its mechanism of action, A18 was identified as an IL-17A inhibitor, resulting in the attenuation of IL-17A signaling and associated diseases in mice. Importantly, A18 also inhibits the NF-κB signaling pathway in different cell types and conditions in vitro and in vivo. In this study, we report that A18 restricts RSV, HSV-1, canine coronavirus, and SARS-CoV-2 multiplication, indicating a broad-spectrum antiviral activity. We also found that A18 can control cytokine and NF-κB induction in RSV-infected cells independently of its antiviral activity. Furthermore, in mice infected with RSV, A18 not only significantly reduces viral titers in the lungs, but also diminishes lung injury. Thus, these results provide evidence that A18 could be used as a broad-spectrum antiviral and may contribute to the development of novel therapeutic targets to control these viral infections and pathogenesis.

Persistence of SARS-CoV-2 RNA shedding and infectivity in immunized population: Prospective study along different epidemiological periods in Argentina.

During the pandemic of COVID-19, numerous waves of infections affected the two hemispheres with different impacts on each country. Throughout these waves, and with the emergence of new variants, health systems and scientists have tried to provide real-time responses to the complex biology of SARS-CoV-2, dealing with different clinical presentations, biological characteristics, and clinical impact of these variants. In this context, knowing the extent period in which an infected individual releases infectious viral particles has important implications for public health. This work aimed to investigate viral RNA shedding and infectivity of SARS-CoV-2 beyond 10 days after symptom onset (SO). A prospective multicenter study was performed between July/2021 and February/2022 on 116 immunized strategic personnel with COVID-19 diagnosed by RT-qPCR, with asymptomatic (7%), mild (91%) or moderate disease (2%). At the time of diagnosis, 70% had 2 doses of vaccines, 26% had 2 plus a booster, and 4% had one dose. After day 10 from SO, sequential nasopharyngeal swabs were taken to perform RT-qPCR, viral isolation, and S gene sequencing when possible. Viral sequences were obtained in 98 samples: 43% were Delta, 16% Lambda, 15% Gamma, 25% Omicron (BA.1) and 1% Non-VOC/VOI, in accordance with the main circulating variants at each moment. SARS-CoV-2 RNA was detected 10 days post SO in 57% of the subjects. Omicron was significantly less persistent. Noteworthy, infective viruses could not be isolated in any of the samples. In conclusion, a 10-days isolation period was useful to prevent further infections, and proved valid for the variants studied. Recently, even shorter periods have been applied, as the Omicron variant is prevalent, and worldwide population is largely vaccinated. In the future, facing the possible emergence of new variants and considering immunological status, a return to 10 days may be necessary.

Evolution of SARS-CoV-2 during the first year of the COVID-19 pandemic in Northwestern Argentina.

Studies about the evolution of SARS-CoV-2 lineages in different backgrounds such as naive populations are still scarce, especially from South America. This work aimed to study the introduction and diversification pattern of SARS-CoV-2 during the first year of the COVID-19 pandemic in the Northwestern Argentina (NWA) region and to analyze the evolutionary dynamics of the main lineages found. In this study, we analyzed a total of 260 SARS-CoV-2 whole-genome sequences from Argentina, belonging to the Provinces of Jujuy, Salta, and Tucumán, from March 31st, 2020, to May 22nd, 2021, which covered the full first wave and the early second wave of the COVID-19 pandemic in Argentina. In the first wave, eight lineages were identified: B.1.499 (76.9%), followed by N.5 (10.2%), B.1.1.274 (3.7%), B.1.1.348 (3.7%), B.1 (2.8%), B.1.600 (0.9%), B.1.1.33 (0.9%) and N.3 (0.9%). During the early second wave, the first-wave lineages were displaced by the introduction of variants of concern (VOC) (Alpha, Gamma), or variants of interest (VOI) (Lambda, Zeta, Epsilon) and other lineages with more limited distribution. Phylodynamic analyses of the B.1.499 and N.5, the two most prevalent lineages in the NWA, revealed that the rate of evolution of lineage N.5 (7.9 × 10-4 substitutions per site per year, s/s/y) was a ∼40% faster than that of lineage B.1.499 (5.6 × 10-4 s/s/y), although both are in the same order of magnitude than other non-VOC lineages. No mutations associated with a biological characteristic of importance were observed as signatures markers of the phylogenetic groups established in Northwestern Argentina, however, single sequences in non-VOC lineages did present mutations of biological importance or associated with VOCs as sporadic events, showing that many of these mutations could emerge from circulation in the general population. This study contributed to the knowledge about the evolution of SARS-CoV-2 in a pre-vaccination and without post-exposure immunization period.

Assessing the hidden diversity underlying consensus sequences of SARS-CoV-2 using VICOS, a novel bioinformatic pipeline for identification of mixed viral populations.

INTRODUCTION: Coinfection with two SARS-CoV-2 viruses is still a very understudied phenomenon. Although next generation sequencing methods are very sensitive to detect heterogeneous viral populations in a sample, there is no standardized method for their characterization, so their clinical and epidemiological importance is unknown. MATERIAL AND METHODS: We developed VICOS (Viral COinfection Surveillance), a new bioinformatic algorithm for variant calling, filtering and statistical analysis to identify samples suspected of being mixed SARS-CoV-2 populations from a large dataset in the framework of a community genomic surveillance. VICOS was used to detect SARS-CoV-2 coinfections in a dataset of 1,097 complete genomes collected between March 2020 and August 2021 in Argentina. RESULTS: We detected 23 cases (2%) of SARS-CoV-2 coinfections. Detailed study of VICOS's results together with additional phylogenetic analysis revealed 3 cases of coinfections by two viruses of the same lineage, 2 cases by viruses of different genetic lineages, 13 were compatible with both coinfection and intra-host evolution, and 5 cases were likely a product of laboratory contamination. DISCUSSION: Intra-sample viral diversity provides important information to understand the transmission dynamics of SARS-CoV-2. Advanced bioinformatics tools, such as VICOS, are a necessary resource to help unveil the hidden diversity of SARS-CoV-2.

Omicron Waves in Argentina: Dynamics of SARS-CoV-2 Lineages BA.1, BA.2 and the Emerging BA.2.12.1 and BA.4/BA.5.

The COVID-19 pandemic has lately been driven by Omicron. This work aimed to study the dynamics of SARS-CoV-2 Omicron lineages during the third and fourth waves of COVID-19 in Argentina. Molecular surveillance was performed on 3431 samples from Argentina, between EW44/2021 and EW31/2022. Sequencing, phylogenetic and phylodynamic analyses were performed. A differential dynamic between the Omicron waves was found. The third wave was associated with lineage BA.1, characterized by a high number of cases, very fast displacement of Delta, doubling times of 3.3 days and a low level of lineage diversity and clustering. In contrast, the fourth wave was longer but associated with a lower number of cases, initially caused by BA.2, and later by BA.4/BA.5, with doubling times of about 10 days. Several BA.2 and BA.4/BA.5 sublineages and introductions were detected, although very few clusters with a constrained geographical distribution were observed, suggesting limited transmission chains. The differential dynamic could be due to waning immunity and an increase in population gatherings in the BA.1 wave, and a boosted population (for vaccination or recent prior immunity for BA.1 infection) in the wave caused by BA2/BA.4/BA.5, which may have limited the establishment of the new lineages.

Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020.

Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019-2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019-2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019-2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets.

Impact of varicella vaccination in Argentina: Seroprevalence in children and adults in a pediatric hospital.

BACKGROUND: Varicella is the primary infection caused by varicella-zoster virus (VZV). In Argentina, the varicella vaccine was introduced in the National Immunization Programme in 2015 as a single dose scheduled at 15 months of age. OBJECTIVES: To estimate VZV seroprevalence in a healthy hospital based population before and after vaccine introduction to the NIP. MATERIAL Y METHODS: Cross-sectional, observational, analytic study. Healthy subjects 1-40 years of age were included between June and December 2019 and tested for VZV-antibodies. Results were compared to data from a similar prevaccination study. RESULTS: Out of 599 samples, 11 indeterminate results were excluded, 424 were positive; overall seroprevalence rate was 72.1% (95 %CI = 68,3-75,8%). No differences were observed between pre and post vaccination studies for overall prevalence or between age groups, except for vaccinated children aged 11-15 (p = 0,005). Rates increased in both periods in subjects aged 6 years or older. Primary vaccine failures were 21%; in subjects <5 years 83% seropositive cases had been vaccinated, in >5 year-olds >90% seropositive cases were associated with a history of infection (OR: 10,4; IC95%: 6,4-16,8; p < 0,001) or household contact (OR:4,8; IC95%: 3,1-7,6; p < 0,001). Vaccination protected against disease (OR: 0.25; 95 %CI: 0.09-0.68; p = 0.004). CONCLUSION: seroprevalence was high in all age groups except in unvaccinated 12 to 15-month infants. Seropositivity was due to vaccination in 15 months to 5 year-old children and to infection in older children.

Longitudinal Study after Sputnik V Vaccination Shows Durable SARS-CoV-2 Neutralizing Antibodies and Reduced Viral Variant Escape to Neutralization over Time.

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic. However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.

First detection and molecular analysis of SARS-CoV-2 from a naturally infected cat from Argentina.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), has rapidly spread worldwide. Studies of transmission of the virus carried out in animals have suggested that certain animals may be susceptible to infection with SARS-CoV-2. The aim of the present study was to investigate the infection of SARS-CoV-2 in pets (18 cats and 20 dogs) from owners previously confirmed as COVID-19-positive. Oropharyngeal and rectal swabs were taken and analyzed by real-time RT-PCR assays, while blood samples were taken for antibody detection. Of the total pets analyzed, one cat was found reactive to SARS-CoV-2 by real-time RT-PCR of an oropharyngeal and a rectal swab. This cat presented only sneezing as a clinical sign. Serological analysis confirmed the presence of antibodies in the serum sample from this cat, as well as in the serum from another cat non-reactive to real-time RT-PCR. Complete sequence and phylogenetic analysis allowed determining that the SARS-CoV-2 genome belonged to the B.1.499 lineage. This lineage has been reported in different provinces of Argentina, mainly in the Metropolitan Area of Buenos Aires. This study notifies the first detection of the natural infection and molecular analysis of SARS-CoV-2 in a cat from Argentina whose owner where COVID-19-positive. Although there is currently no evidence that cats can spread COVID-19, results suggest that health authorities should test pets with COVID-19-positive owners.

Clinical and epidemiological study of acute lower respiratory tract infections caused by adenovirus in hospitalized children. Nineteen years of active epidemiological surveillance. / Estudio clínico-epidemiológico de las infecciones respiratorias agudas bajas causadas por adenovirus en niños hospitalizados. Diecinueve años de vigilancia epidemiológica activa.

INTRODUCTION: Acute lower respiratory tract infection (ALRTI) caused by adenovirus is a major cause of morbidity and mortality in children. OBJECTIVES: To describe the clinical and epidemiological pattern and associated factors in hospitalized children. METHODS: Cross-sectional study in children admitted due to ALRTI to Hospital de Niños "Ricardo Gutiérrez," in the Autonomous City of Buenos Aires, between 2000 and 2018. Viral diagnosis was done by indirect immunofluorescence in nasopharyngeal secretions. The clinical and epidemiological characteristics of adenovirus infection were compared to other respiratory viruses (respiratory syncytial virus, influenza, and parainfluenza). A multiple logistic regression was done to identify independent predictors of infection. RESULTS: Out of 16 018 patients with ALRTI, 13 545 were tested for respiratory viruses; 6047 (45 %) had a positive result. Adenovirus was the least common agent (4.4 % [265] of cases); it tended towards a reduction over the study period (peak in 2003) and circulated throughout the year (peak in July). In total, 63.8 % of patients were males; median age: 11 months (interquartile range: 6-20). The most common clinical presentation was pneumonia (63 %). Prior admissions due to respiratory conditions were seen in 50 %; 15.6 % were readmissions; 58.3 % had comorbidities. Ventilatory support was required by 19.2 % and complications were recorded in 44 %. The fatality rate was 7.7 %. Adenovirus infection was associated with age ≥ 12 months, male sex, clinical presentation of pneumonia, prior admissions due to respiratory conditions, and readmissions. CONCLUSIONS: Adenoviruses were less common than other respiratory viruses, although their morbidity and mortality were important.

Introducción. La infección respiratoria aguda baja por adenovirus es una importante causa de morbimortalidad en niños. Objetivos: Describir el patrón clínicoepidemiológico y los factores asociados en niños hospitalizados. Métodos. Estudio transversal en niños ingresados por infección respiratoria aguda baja al Hospital de Niños Ricardo Gutiérrez, Buenos Aires, en 2000-2018. El diagnóstico viral se realizó mediante inmunofluorescencia indirecta en secreciones nasofaríngeas. Se compararon características clínico-epidemiológicas de infección por adenovirus con otros virus respiratorios (virus sincicial respiratorio, influenza y parainfluenza). Se utilizó regresión logística múltiple para identificar predictores independientes de infección. Resultados. De 16018 pacientes con infección respiratoria aguda baja, 13545 fueron testeados para virus respiratorios y 6047 (el 45 %) fueron positivos. Adenovirus fue el agente menos frecuente [el 4,4 % (265) de los casos]; presentó una tendencia en descenso durante todo el período estudiado (pico en 2003) y circuló durante todo el año (pico en julio). El 63,8 % eran varones; mediana de edad: 11 meses (rango intercuartílico: 6-20). La presentación clínica más frecuente fue neumonía (el 63 %). El 50 % tenía internaciones previas por causa respiratoria; el 15,6 % eran reingresos; el 58,3 % tenía comorbilidades. El 19,2 % requirió asistencia ventilatoria; el 44 % registró complicaciones. La letalidad fue del 7,7 %. La infección por adenovirus se asoció a edad ≥ 12 meses, sexo masculino, presentación clínica de neumonía, internaciones previas por causas respiratorias y reinternaciones. Conclusiones. Los adenovirus fueron detectados con menor frecuencia que los otros virus respiratorios, aunque presentaron un importante perfil de morbimortalidad.