Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study.

Background: At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or "Long COVID". The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. The large US RECOVER study identified four clusters of subjects with PCC according to their presenting symptoms. However, the long-term clinical implications of PCC remain unknown. Methods: We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modelled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach. Findings: The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16.5-23.5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7.6%) recovered from PCC during follow-up; almost all of them (n = 24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC. Interpretation: Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, are associated with the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems. Funding: Fundació Lluita contra les Infeccions.

Fulminant myocarditis following SARS-CoV-2 mRNA vaccination rescued with venoarterial ECMO: A report of two cases.

INTRODUCTION: Cases of myocarditis after COVID-19 messenger RNA (mRNA) vaccines administration have been reported. Although the majority follow a mild course, fulminant presentations may occur. In these cases, cardiopulmonary support with venoarterial extracorporeal membrane oxygenation (V-A ECMO) may be needed. RESULTS: We present two cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-CoV2 vaccine. One of the cases was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab using the Seldinger technique. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Whereas an endomyocardial biopsy was performed in both, a definite microscopic diagnosis just could be reached in one of them. Treatment was the same, using 1000mg of methylprednisolone/day for three days. A cardiac magnetic resonance was performed ten days after admission, showing a significant improvement of the left ventricular ejection fraction and diffuse oedema and subepicardial contrast intake in different segments. Both cases were discharged fully recovered, with CPC 1. CONCLUSIONS: COVID-19 vaccine-associated fulminant myocarditis has a high morbidity and mortality but presents a high potential for recovery. V-A ECMO should be established in cases with refractory cardiogenic shock during the acute phase.

Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals.

Mass vaccination campaigns reduced COVID-19 incidence and severity. Here, we evaluated the immune responses developed in SARS-CoV-2-uninfected patients with predominantly antibody-deficiencies (PAD) after three mRNA-1273 vaccine doses. PAD patients were classified based on their immunodeficiency: unclassified primary antibody-deficiency (unPAD, n = 9), common variable immunodeficiency (CVID, n = 12), combined immunodeficiency (CID, n = 1), and thymoma with immunodeficiency (TID, n = 1). unPAD patients and healthy controls (HCs, n = 10) developed similar vaccine-induced humoral responses after two doses. However, CVID patients showed reduced binding and neutralizing titers compared to HCs. Of interest, these PAD groups showed lower levels of Spike-specific IFN-γ-producing cells. CVID individuals also presented diminished CD8+T cells. CID and TID patients developed cellular but not humoral responses. Although the third vaccine dose boosted humoral responses in most PAD patients, it had limited effect on expanding cellular immunity. Vaccine-induced immune responses in PAD individuals are heterogeneous, and should be immunomonitored to define a personalized therapeutic strategies.

Efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies: A cross sectional study.

SARS-CoV-2 vaccination is the most effective strategy to protect individuals with haematologic malignancies against severe COVID-19, while eliciting limited vaccine responses. We characterized the humoral responses following 3 mo after mRNA-based vaccines in individuals at different plasma-cell disease stages: monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma on first-line therapy (MM), compared with a healthy population. Plasma samples from uninfected MM patients showed lower SARS-CoV-2-specific antibody levels and neutralization capacity compared with MGUS, SMM, and healthy individuals. Importantly, COVID-19 recovered MM individuals presented significantly higher plasma neutralization capacity compared with their uninfected counterparts, highlighting that hybrid immunity elicit stronger immunity even in this immunocompromised population. No differences in the vaccine-induced humoral responses were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, MGUS and SMM patients could be SARS-CoV-2 vaccinated following the vaccine recommendations for the general population, whereas a tailored monitoring of the vaccine-induced immune responses should be considered in uninfected MM patients.

Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities.

BACKGROUND: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine. METHODS: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group. RESULTS: three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels. CONCLUSIONS: although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.

Diagnóstico ecográfico de la insuficiencia respiratoria postoperatoria aguda tras timectomía / Role of ecography in diagnostic of postoperative acute respiratory failure after timectomy / Diagnóstico ultrassonográfico da insuficiência respiratória aguda pós-operatória após timectomia

Resumen: La miastenia gravis es una enfermedad autoinmune que puede alterar las capacidades físicas de los pacientes. La timectomía es una de las opciones terapéuticas. Su postoperatorio puede ser complicado por la propia enfermedad o por lesiones intraoperatorias de estructuras nerviosas. Presentamos a una mujer de 66 años intervenida de timectomía por timoma que causa miastenia gravis. Durante la intervención se reseca el nervio frénico izquierdo. En el postoperatorio inmediato presenta insuficiencia respiratoria aguda, por lo que se realiza ecografía pulmonar anodina y ecografía diafragmática que muestra fracción de acortamiento de 10% en el lado derecho y ausencia de contractilidad en el lado izquierdo. La paciente precisó ventilación mecánica no invasiva durante seis días y traqueotomía para avanzar en el destete respiratorio, siendo dada de alta a planta finalmente en respiración espontánea con cánula fenestrada por traqueotomía. La ecografía diafragmática supone una técnica diagnóstica disponible a la cabecera del paciente, útil en situaciones urgentes gracias a su rápida realización y a que complementa la valoración clínica en el diagnóstico de la insuficiencia respiratoria aguda postquirúrgica.

Abstract: Myasthenia gravis is an autoimmune disease that can alter the physical abilities of patients. Thymectomy is one of the therapeutic options. The postoperatory may be complicated by the disease itself or by intraoperative lesions of nerve structures. Case of 66-year-old woman with myasthenia gravis undergoing thymectomy. The left phrenic nerve was resected. In the immediate postoperative period, the patient presented acute respiratory failure. A lung ultrasound is performed, being anodyne. The diaphragmatic ultrasound proved a 10% of thickening fraction on the right side and absence of contractility on the left side. The patient required non-invasive mechanical ventilation for six days, tracheotomy was performed to succeed the respiratory weaning. The patient was transferred to ward in spontaneous ventilation. The diaphragmatic ultrasound is a useful and portable diagnostic technique, mainly in urgent situations due to the rapidity of its implementation. It complements the clinical assessment in the diagnosis of acute postoperative respiratory failure.

Resumo: A miastenia gravis é uma doença auto-imune que pode alterar as capacidades físicas dos pacientes. A timectomia é uma das opções de tratamento. O pós-operatório pode ser complicado pela própria doença ou por lesões intra-operatória de estruturas nervosas. Apresentamos uma mulher de 66 anos submetida a timectomia por timoma que causa miastenia gravis. Durante a cirurgia, o nervo frênico esquerdo é ressecado. No pós-operatório imediato, a paciente apresentou insuficiência respiratória aguda, de modo que foram realizadas uma ultrassonografia pulmonar anódino e ecografia diafragmática, mostrando uma fração de encurtamento de 10% no lado direito e ausência de contratilidade no lado esquerdo. A paciente requeriu de ventilação mecânica não invasiva por 6 dias e a realização de uma traqueotomia para avançar no desmame respiratório, sendo dada de alta da UTI respirando espontâneamente com uma cânula de traqueostomia fenestrada. O ultrassom diafragmático é uma técnica de diagnóstico disponível à beira do leito, útil em situações urgentes devido à rapidez do seu desempenho e que complementa a avaliação clínica no diagnóstico de insuficiência respiratória aguda pós-operatória.

Antipsychotic medication and oropharyngeal dysphagia: systematic review.

The association between antipsychotics (also known as neuroleptics) and oropharyngeal dysphagia (OD) has been suggested in several case reports. The purpose of this systematic review was to examine the effect of antipsychotic medication on OD. A systematic literature search was carried out according to PRISMA guidelines using the electronic databases Pubmed and Embase. In Pubmed, we used the MeSH terms 'antipsychotic agents' OR 'tranquilizing agents' combined with 'deglutition disorders' OR 'deglutition'. In Embase, we used the Emtree terms 'neuroleptic agents' combined with 'swallowing' OR 'dysphagia'. Two reviewers assessed the eligibility of each report independently. The level of evidence of the included studies was also assessed according to pre-established criteria. Case reports were excluded. We found 18 clinical studies of dysphagia related to antipsychotics: 12 were related both to typical and atypical antipsychotics, four to atypical antipsychotics and two to typical antipsychotics. According to the clinical studies included, prevalence of patients with swallowing problems taking antipsychotics ranged from 21.9 to 69.5% whereas prevalence of patients without swallowing problems taking antipsychotics ranged from 5 to 30.5%. The available evidence suggests considering an etiology of dysphagia in patients with swallowing problems who are taking antipsychotics, even if no other symptoms are present. Although few general conclusions can be drawn from current evidence, both typical and atypical antipsychotics can be associated with OD.

Association of screen time use and language development in Hispanic toddlers: a cross-sectional and longitudinal study.

This study examined the association between screen media use, media content, and language development among 119 Hispanic infants and toddlers. Children and their caregivers were recruited through an urban, Early Head Start program. Duration and content of screen media exposure was measured through a 24-hour recall questionnaire, and language development was measured at baseline and at 1-year follow up. Children in the sample spent an average of 3.29 hours engaged with screen media (median 2.5 hours per day). In both cross-sectional and longitudinal analyses, children who watched over 2 hours of television per day had increased odds of low communication scores. Whereas child-directed media was associated with low language scores, adult-directed media was not. Our findings support the mounting literature on the deleterious impacts of screen media in toddler's language development. Guidance and alternatives to screen media use should be available to families in pediatric practices and early childhood centers.