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.

Assessment of the outcomes of SARS-CoV-2 infection in children and young people followed at Portuguese pediatric rheumatology clinics.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) generally appears to have milder clinical symptoms and fewer laboratory abnormalities in children. It remains unknown whether children and young people with inflammatory chronic diseases who acquire SARS-CoV-2 infection have a more severe course, due to either underlying disease or immunosuppressive treatments. OBJECTIVES: To assess the epidemiological features and clinical outcomes of children and young people with inflammatory chronic diseases followed at Pediatric Rheumatology Clinics who were infected with SARS-CoV-2. METHODS: A multicentric prospective observational study was performed. Data on demographic variables, clinical features and treatment were collected between March 2020 and September 2021, using the Rheumatic Diseases Portuguese Register (Reuma.pt) and complemented with data from the hospital clinical records. RESULTS: Thirty-four patients were included, 62% were female, with a median age of 13 [8-16] years and a median time of inflammatory chronic disease of 6 [3-10] years. The most common diagnoses were juvenile idiopathic arthritis (n=22, 64.7%), juvenile dermatomyositis (n=3, 8.8%) and idiopathic uveitis (n=3, 8.8%). Twenty patients were on conventional synthetic disease modifying drugs (csDMARDs) and 10 on biologic DMARDs (bDMARDs). Five patients had an active inflammatory disease at the time of infection (low activity). Seven patients had an asymptomatic infection while 27 patients (79%) had symptoms: cough (n=12), fever (n=11), rhinorrhea (n=10), headache (n=8), malaise (n=8), fatigue (n=7), anosmia (n=5), myalgia (n=5),dysgeusia (n=4), odynophagia (n=4), chest pain (n=2), diarrhea (n=2), arthralgia (n=1), vomiting (n=1) and conjunctivitis (n=1). No patient required hospitalization or directed treatment, and all recovered without sequelae. In 8 patients there was a change in the baseline medication during the infection: suspension of bDMARDs (n=4), reduction of bDMARDs (n=1), suspension of csDMARDs (n=4) and reduction of csDMARDs (n=2). Only in one patient with juvenile dermatomyositis (who discontinued bDMARDs and csDMARDs), the underlying disease worsened. CONCLUSIONS: This is the first study involving children with inflammatory chronic diseases followed at Rheumatology Clinics and SARS-CoV-2 infection in Portugal. In our cohort, mild illness was predominant, which is consistent with the literature. There was no need for hospitalization or specific treatment, and, in most cases, no worsening of the underlying disease was identified.

Development of a Prediction Model for COVID-19 Acute Respiratory Distress Syndrome in Patients With Rheumatic Diseases: Results From the Global Rheumatology Alliance Registry.

OBJECTIVE: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. METHODS: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. RESULTS: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. CONCLUSION: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.

Risk Factors for Infection, Predictors of Severe Disease, and Antibody Response to COVID-19 in Patients With Inflammatory Rheumatic Diseases in Portugal-A Multicenter, Nationwide Study.

Objective: To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients. Methods: Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register-Reuma.pt-during the first 6 months of the pandemic. We compared patients with COVID-19 with those who did not develop the disease and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. IgG antibodies against SARS-CoV-2 were measured ≥3 months after infection and results were compared with matched controls. Results: 162 cases of COVID-19 were registered in a total of 6,363 appointments. Patients treated with TNF inhibitors (TNFi; OR = 0.160, 95% CI 0.099-0.260, P < 0.001) and tocilizumab (OR 0.147, 95% CI 0.053-0.408, P < 0.001) had reduced odds of infection. Further, TNFi tended to be protective of severe and critical disease. Older age, major comorbidities, and rituximab were associated with an increased risk of infection and worse prognosis. Most patients with inflammatory RMDs (86.2%) developed a robust antibody response. Seroconversion was associated with symptomatic disease (OR 13.46, 95% CI 2.21-81.85, P = 0.005) and tended to be blunted by TNFi (OR 0.17, 95% CI 0.03-1.05; P = 0.057). Conclusions: TNFi and tocilizumab reduced the risk of infection by SARS-CoV-2. Treatment with TNFi also tended to reduce rates of severe disease and seroconversion. Older age, general comorbidities and rituximab were associated with increased risk for infection and worse prognosis, in line with previous reports. Most patients with RMDs developed a proper antibody response after COVID-19, particularly if they had symptomatic disease.

Anthropogenic Infection of Domestic Cats With SARS-CoV-2 Alpha Variant B.1.1.7 Lineage in Buenos Aires.

SARS-CoV-2 reverse zoonosis, particularly to domestic animals, and the potential role of infected animals in perpetuating the spread of the virus is an issue of increasing concern. In this case report, we identified the natural infection of two cats by SARS-CoV-2, in Argentina, whose owner had been previously infected by SARS-CoV-2. Viral genetic material was detected in feline oropharyngeal (OP) and rectal (R) swab by RT-qPCR, and sequence analysis revealed that the virus infecting the owner and one cat were genetically similar. The alpha variant (B.1.1.7 lineage) was identified with a unique additional mutation, strongly suggesting human-to-cat route of transmission. This study reinforces the One Health concept and the importance of integrating human, animal, and environmental perspectives to promptly address relevant health issues.

[Building COVID-19's semiology: The blind wise men and the elephant]. / Construyendo la semiología de la COVID-19: los sabios ciegos y el elefante.

OBJECTIVE: Construction of mild and moderate COVID-19's semiology between patients and professionals in primary care. METHOD: Qualitative investigation in a phenomenological theoretical frame, from an epistemic justice position, settled in Catalonia, primary care settings, during the first wave of COVID-19 pandemic (April-May 2020). 15 patients and 9 professionals participated. Data collection was done through semi-structured phone interviews to patients with a microbiological confirmed diagnostic of COVID-19 and followed at primary care and semi-structured narratives of professionals. Data were triangled by the three authors. RESULTS: We described the most common symptoms (fever, cough, shortness of breath, fatigue, loss of appetite, muscular and joint pain, and high airways symptoms), those that worry them the most, hesitancy about symptoms and semiology's temporality according to the descriptions done by patients. CONCLUSIONS: Official protocols should include other symptoms as fatigue, loss of appetite, muscle and joint aches and high airways symptoms as frequent symptoms of COVID-19 attending to the stories of patients. Those unspecified symptoms can be unnoticed by patients and professionals and can delay the detection of disease and the contact tracing in primary care. It is necessary to obtain a detailed description of the symptoms and avoid translating them into pre-established medical terms that with their meaning substitute and make the patients' report invisible, turning professionals deaf and blind to a new disease and making more difficult for them to build the narration of disease.

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

AIM: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. METHODS: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. RESULTS: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. CONCLUSIONS: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

Construyendo la semiología de la COVID-19: los sabios ciegos y el elefante Building COVID-19’s semiology: the blind men and the elephant

Objetivo: Construir entre pacientes y profesionales la semiología de la COVID-19 leve y moderada atendida en atención primaria. Método: Investigación cualitativa con enfoque teórico fenomenológico, desde un marco teórico de justicia epistémica, realizada en Cataluña, en el ámbito de la atención primaria, durante la primera ola de la pandemia (abril-mayo de 2020). Participaron 15 pacientes y 9 profesionales. La recogida de datos se realizó mediante entrevistas telefónicas semiestructuradas a pacientes con COVID-19 confirmada con prueba de reacción en cadena de la polimerasa y seguidas en atención primaria, y por las descripciones narrativas semiestructuradas de profesionales. Los datos fueron triangulados por las autoras. Resultados: Se describen los síntomas más frecuentes (fiebre, tos, disnea, cansancio, inapetencia, dolor muscular y articular, y síntomas de vías respiratorias altas) siguiendo la descripción de las personas afectadas y los síntomas que más preocupan. Se analizan las dudas sobre los síntomas y la temporalidad de la semiología. Conclusiones: Los protocolos oficiales deberían incluir el cansancio, la inapetencia, el dolor muscular y articular, y los síntomas de vías respiratorias altas, como manifestaciones frecuentes de la COVID-19, atendiendo al relato de las pacientes. Estos síntomas pueden pasar desapercibidos en las pacientes y para las profesionales puede suponer un retraso en la detección de la enfermedad y el estudio de contactos. Es necesario obtener una descripción detallada de los síntomas y evitar traducirlos a términos médicos preestablecidos, pues con su significado sustituyen e invisibilizan la narración de los pacientes, vuelven a los profesionales sordos y ciegos ante una nueva enfermedad, y dificultan la creación de un relato.

Cost-Effective Method to Perform SARS-CoV-2 Variant Surveillance: Detection of Alpha, Gamma, Lambda, Delta, Epsilon, and Zeta in Argentina.

SARS-CoV-2 variants with concerning characteristics have emerged since the end of 2020. Surveillance of SARS-CoV-2 variants was performed on a total of 4,851 samples from the capital city and 10 provinces of Argentina, during 51 epidemiological weeks (EWs) that covered the end of the first wave and the ongoing second wave of the COVID-19 pandemic in the country (EW 44/2020 to EW 41/2021). The surveillance strategy was mainly based on Sanger sequencing of a Spike coding region that allows the identification of signature mutations associated with variants. In addition, whole-genome sequences were obtained from 637 samples. The main variants found were Gamma and Lambda, and to a lesser extent, Alpha, Zeta, and Epsilon, and more recently, Delta. Whereas, Gamma dominated in different regions of the country, both Gamma and Lambda prevailed in the most populated area, the metropolitan region of Buenos Aires. The lineages that circulated on the first wave were replaced by emergent variants in a term of a few weeks. At the end of the ongoing second wave, Delta began to be detected, replacing Gamma and Lambda. This scenario is consistent with the Latin American variant landscape, so far characterized by a concurrent increase in Delta circulation and a stabilization in the number of cases. The cost-effective surveillance protocol presented here allowed for a rapid response in a resource-limited setting, added information on the expansion of Lambda in South America, and contributed to the implementation of public health measures to control the disease spread in Argentina.

Increased circulating levels of angiotensin-(1-7) in severely ill COVID-19 patients.

This letter reports an unexpected increase of the ACE2 product angiotensin-(1-7) and a parallel decrease of its substrate angiotensin II, suggesting a dysregulation of the renin-angiotensin system towards angiotensin-(1-7) formation in #COVID19 patients https://bit.ly/3xFXuTU.

ACE2 in the renin-angiotensin system.

In 2020 we are celebrating the 20th anniversary of the angiotensin-converting enzyme 2 (ACE2) discovery. This event was a landmark that shaped the way that we see the renin-angiotensin system (RAS) today. ACE2 is an important molecular hub that connects the RAS classical arm, formed mainly by the octapeptide angiotensin II (Ang II) and its receptor AT1, with the RAS alternative or protective arm, formed mainly by the heptapeptides Ang-(1-7) and alamandine, and their receptors, Mas and MrgD, respectively. In this work we reviewed classical and modern literature to describe how ACE2 is a critical component of the protective arm, particularly in the context of the cardiac function, coagulation homeostasis and immune system. We also review recent literature to present a critical view of the role of ACE2 and RAS in the SARS-CoV-2 pandemic.