Multisystem inflammatory syndrome in children and SARS-CoV-2 variants: a two-year ambispective multicentric cohort study in Catalonia, Spain.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe disease temporarily related to SARS-CoV-2. We aimed to describe the epidemiological, clinical, and laboratory findings of all MIS-C cases diagnosed in children < 18 years old in Catalonia (Spain) to study their trend throughout the pandemic. This was a multicenter ambispective observational cohort study (April 2020-April 2022). Data were obtained from the COVID-19 Catalan surveillance system and from all hospitals in Catalonia. We analyzed MIS-C cases regarding SARS-CoV-2 variants for demographics, symptoms, severity, monthly MIS-C incidence, ratio between MIS-C and accumulated COVID-19 cases, and associated rate ratios (RR). Among 555,848 SARS-CoV-2 infections, 152 children were diagnosed with MIS-C. The monthly MIS-C incidence was 4.1 (95% CI: 3.4-4.8) per 1,000,000 people, and 273 (95% CI: 230-316) per 1,000,000 SARS-CoV-2 infections (i.e., one case per 3,700 SARS-CoV-2 infections). During the Omicron period, the MIS-C RR was 8.2 (95% CI: 5.7-11.7) per 1,000,000 SARS-CoV-2 infections, which was significantly lower (p < 0.001) than that for previous variant periods in all age groups. The median [IQR] age of MIS-C was 8 [4-11] years, 62.5% male, and 80.2% without comorbidities. Common symptoms were gastrointestinal findings (88.2%) and fever > 39 °C (81.6%); nearly 40% had an abnormal echocardiography, and 7% had coronary aneurysm. Clinical manifestations and laboratory data were not different throughout the variant periods (p > 0.05).  Conclusion: The RR between MIS-C cases and SARS-CoV-2 infections was significantly lower in the Omicron period for all age groups, including those not vaccinated, suggesting that the variant could be the main factor for this shift in the MISC trend. Regardless of variant type, the patients had similar phenotypes and severity throughout the pandemic. What is Known: • Before our study, only two publications investigated the incidence of MIS-C regarding SARS-CoV-2 variants in Europe, one from Southeast England and another from Denmark. What is New: • To our knowledge, this is the first study investigating MIS-C incidence in Southern Europe, with the ability to recruit all MIS-C cases in a determined area and analyze the rate ratio for MIS-C among SARS-CoV-2 infections throughout variant periods. • We found a lower rate ratio of MISC/infections with SARS-CoV-2 in the Omicron period for all age groups, including those not eligible for vaccination, suggesting that the variant could be the main factor for this shift in the MISC trend.

Phase angle and COVID-19: A systematic review with meta-analysis.

Phase angle (PhA) has been identified as a poor prognostic factor in patients with COVID-19. This study aimed to achieve a systematic review, where we discussed the potential role of PhA value as a prognostic marker of adverse clinical outcomes such as mortality and complication in hospitalized with SARS-CoV2 infection and established the strength of recommendations for use. A systematic literature review with meta-analysis was done in the main electronic databases from 2020 to January 2023. The selected articles had to investigate adverse consequences of the COVID-19 population and raw bioimpedance parameters such as PhA and published in peer-reviewed journals. GRADE tools regarded the quality of the methodology. The review protocol was registered in PROSPERO. Only eight studies, 483 studies, were eligible for the analysis. In general, differences in PhA were seen between the comparative study groups. Patients with a low PhA experienced poor outcomes. A low PhA was associated with a significantly increased mortality risk [RR: 2.44; 95% CI (1.20-4.99), p = 0.01; I2 = 79% (p = 0.0008)] and higher complications risk [OR: 3.47, 95% CI (1.16 - 10.37), p = 0.03; I2 = 82% (p = 0.004)] in COVID-19 patients. Our analysis showed four evidence-based recommendations on the prognostic value of PhA with two strong recommendations, one of moderate and another of low-moderate quality, for predicting mortality and complications, respectively. We recommend using PhA as a prognostic marker for mortality and complications in this population. Although the results are promising, future studies must identify the PhA cut-off to guide therapeutic decisions more precisely.Registration code in PROSPERO: CRD42023391044.

Predictors of Sarcopenia in Outpatients with Post-Critical SARS-CoV2 Disease. Nutritional Ultrasound of Rectus Femoris Muscle, a Potential Tool.

Background and Objectives: The loss of muscle mass in post-critical COVID-19 outpatients is difficult to assess due to the limitations of techniques and the high prevalence of obesity. Ultrasound is an emerging technique for evaluating body composition. The aim is to evaluate sarcopenia and its risk factors, determining ultrasound usefulness as a potential tool for this purpose according to established techniques, such as the bioimpedance vector analysis (BIVA), handgrip strength, and timed up-and-go test. Methods: This is a transversal study of 30 post-critical COVID-19 outpatients. We evaluated nutritional status by ultrasound (Rectus Femoris-cross-sectional-area (RF-CSA), thickness, and subcutaneous-adipose-tissue), BIVA, handgrip strength, timed up-and-go test, and clinical variables during admission. Results: According to The European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity (ESPEN&EASO) Consensus for Sarcopenic and Obesity, in terms of excess fat mass and decreased lean mass, the prevalence of class-1 sarcopenic obesity was 23.4% (n = 7), and class-2 sarcopenic obesity was 33.3% (n = 10) in our study. A total of 46.7% (n = 14) of patients had a handgrip strength below the 10th percentile, and 30% (n = 9) achieved a time greater than 10s in the timed up-and-go test. There were strong correlations between the different techniques that evaluated the morphological (BIVA, Ultrasound) and functional measurements of muscle. Intensive care unit stay, mechanical ventilation, and age all conditioned the presence of sarcopenia in COVID-19 outpatients (R2 = 0.488, p = 0.002). Predictive models for sarcopenic diagnosis based on a skeletal muscle index estimation were established by RF-CSA (R2 0.792, standard error of estimate (SEE) 1.10, p < 0.001), muscle-thickness (R2 0.774, SEE 1.14, p < 0.001), and handgrip strength (R2 0.856, SEE 0.92, p < 0.001). RF-CSA/weight of 5.3 cm2/kg × 100 was the cut-off value for predicting sarcopenia in post-critical COVID-19 outpatients, with 88.2 sensitivity and 69.2% specificity. Conclusion: More than half of the post-critical COVID-19 survivors had sarcopenic obesity and functional impairment of handgrip strength. Intensive care unit stay, age, and mechanical ventilation all predict sarcopenia. An ultrasound, when applied to the assessment of body composition in post-critical COVID-19 patients, provided the possibility of assessing sarcopenia in this population.

Overhydration Assessed Using Bioelectrical Impedance Vector Analysis Adversely Affects 90-Day Clinical Outcome among SARS-CoV2 Patients: A New Approach.

BACKGROUND: COVID-19 has taken on pandemic proportions with growing interest in prognostic factors. Overhydration is a risk factor for mortality in several medical conditions with its role in COVID-19, assessed with bioelectrical impedance (BI), gaining research interest. COVID-19 affects hydration status. The aim was to determine the hydration predictive role on 90 d survival COVID-19 and to compare BI assessments with traditional measures of hydration. METHODS: We studied 127 consecutive COVID-19 patients. Hydration status was estimated using a 50 kHz phase-sensitive BI and estimated, compared with clinical scores and laboratory markers to predict mortality. RESULTS: Non-surviving COVID-19 patients had significantly higher hydration 85.2% (76.9-89.3) vs. 73.7% (73.2-82.1) and extracellular water/total body water (ECW/TBW) 0.67 (0.59-0.75) vs. 0.54 (0.48-0.61) (p = 0.001, respectively), compared to surviving. Patients in the highest hydration tertile had increased mortality (p = 0.012), Intensive Care Unit (ICU) admission (p = 0.027), COVID-19 SEIMC score (p = 0.003), and inflammation biomarkers [CRP/prealbumin (p = 0.011)]. Multivariate analysis revealed that hydration status was associated with increased mortality. HR was 2.967 (95%CI, 1.459-6.032, p < 0.001) for hydration and 2.528 (95%CI, 1.664-3.843, p < 0.001) for ECW/TBW, which were significantly greater than traditional measures: CRP/prealbumin 3.057(95%CI, 0.906-10.308, p = 0.072) or BUN/creatinine 1.861 (95%CI, 1.375-2.520, p < 0.001). Hydration > 76.15% or ECW/TBW > 0.58 were the cut-off values predicting COVID-19 mortality with 81.3% and 93.8% sensitivity and 64 and 67.6% specificity, respectively. Hydration status offers a sensitive and specific prognostic test at admission, compared to established poor prognosis parameters. CONCLUSIONS AND RELEVANCE: Overhydration, indicated as high hydration (>76.15%) and ECW/TBW (>0.58), were significant predictors of COVID-19 mortality. These findings suggest that hydration evaluation with 50 kHz phase-sensitive BI measurements should be routinely included in the clinical assessment of COVID-19 patients at hospital admission, to identify increased mortality risk patients and assist medical care.

Phase angle and standardized phase angle from bioelectrical impedance measurements as a prognostic factor for mortality at 90 days in patients with COVID-19: A longitudinal cohort study.

BACKGROUND & AIMS: Severe acute COVID-19 has taken on pandemic proportions with growing interest in identification of prognostic factors for mortality. Standardized bioelectrical impedance (BI) phase angle (SPhA), which is PhA adjusted by age and sex, has been related to mortality in patients with several diseases but never investigated in COVID-19. Inflammation, a consequence of COVID-19 infection, affects fluid status (hydration) and can be identified with PhA. The aim of this study was to determine the predictive role of PhA on 90 days survival of adults with COVID-19. METHODS: We studied 127 consecutive patients diagnosed with COVID-19. BI measurements determined with a 50 kHz phase-sensitive BI device, body composition parameters and laboratory markers were evaluated as predictors of mortality. RESULTS: Non-surviving COVID-19 patients had significantly lower PhA and SPhA values (p < 0.001) and increased hydration (p < 0.001) compared to surviving patients. Patients in the lowest SPhA quartile had increased (p < 0.001) mortality and hospital stay, hyperhydration (p < 0.001), increased inflammation biomarkers [CRP (p < 0.001)], decreased nutritional parameters: body mass cell index [BCMI (p < 0.001) albumin (p < 0.001)], and reduced other biomarkers [D-dimer (p = 0.002)]. Multivariate analysis (Cox regression) revealed that PhA and hydration status, adjusted for age, sex, BMI, diabetes, hypertension, dyslipidaemia or heart disease, were associated (p < 0.001) with increased mortality. The hazard ratio was 2.48 (95% CI, 1.60-3.84, p < 0.001) for PhA and 1.12 (95% CI, 1.04-1.20, p = 0.003) for hydration percentage. PhA <3.95° was the cut-off for predicting mortality in acute COVID-19 with 93.8% sensitivity and 66.7% specificity. PhA offers greater sensitivity as a predictive prognostic test at admission, compared to the established analytical parameters of poor prognosis (CRP, lymphocytes, prealbumin). CONCLUSIONS: Low PhA (<3.95°), independent of age, sex, BMI, and comorbidities, is a significant predictor of mortality risk in COVID-19. These findings suggest that the evaluation of body composition with single-frequency phase-sensitive BI measurements should be included in the routine clinical assessment of COVID-19 patients at hospital admission to identify patients at increased mortality risk.