Occurrence and outcomes of possible superadded infections in older adults with COVID-19—cohort study

Purpose: Current guidance discourages use of antibiotics in COVID-19. However, in older adults, superadded infection may be common and require treatment. Our aim was to investigate the occurrence and outcomes from possible superadded infections, occurring within 2 weeks of hospitalization, in older adults with COVID-19. Methods: This was a single centre, observational cohort study. We collected data from patients admitted to older adult wards who had tested positive for the Sars-CoV-2 virus on viral PCR between 1st October and 1st December 2020. The primary outcome was inpatient death occurring within 90 days of COVID-19 diagnosis. The secondary outcome was length of stay in hospital. Associations were described using univariable and multivariable models, and time to event data. Results: Of 266 patients with COVID-19, 43% (115) had evidence of superadded infections (91 with positive bacterial cultures and 36 instances of radiological lobar consolidation). Patients with superadded infections were more likely to die (45.2 versus 30.7%, p = 0.020) and had an increased length of stay (23 versus 18 days, p = 0.026). Conclusions: Recommendations to avoid antibiotics in COVID-19 may not be applicable to an older adult population. Assessing for possible superadded infections is warranted in this group

Comparison between first and second wave of COVID-19 outbreak in older people. The COPE multicentre European observational cohort study

Background: Effective shielding measures and virus mutations have progressively modified the disease between the waves, likewise health care systems have adapted to the outbreak. Our aim was to compare clinical outcomes for older people with COVID-19 in Wave 1 (W1) and 2 (W2). Methods: All data, including the Clinical Frailty Scale (CFS), were collected for COVID-19 consecutive patients, aged ≥65, from thirteen hospitals, in W1 (February-June 2020) and W2 (October 2020-March 2021). The primary outcome was mortality (time to mortality and 28-day mortality). Data were analysed with multilevel Cox proportional hazards, linear and logistic regression models, adjusted for wave baseline demographic and clinical characteristics. Results: Data from 611 people admitted in W2 were added to and compared with data collected during W1 (N = 1340). Patients admitted in W2 were of similar age, median [IQR], W2 = 79 [73-84]; W1 = 80 [74-86]; had a greater proportion of men (59.4% vs 53.0%); had lower 28-day mortality (29.1% vs 40.0%), compared to W1. For combined W1-W2 sample, W2 was independently associated with improved survival: time-to-mortality aHR= 0.78 (95%CI 0.65-0.93), 28-day mortality aOR = 0.80 (95%CI 0.62-1.03). W2 was associated with increased length of hospital stay aHR = 0.69 (95%CI 0.59-0.81). Patients in W2 were less frail, CFS (adjusted mean difference [aMD]=-0.50, 95%CI -0.81, -0.18), as well as presented with lower CRP (aMD=-22.52, 95%CI -32.00, -13.04). Conclusions: COVID-19 older adults in W2 were less likely to die than during W1. Patients presented to hospital during W2 were less frail and with lower disease severity and less likely to have renal decline

Prognostic value of estimated glomerular filtration rate in hospitalised older patients (over 65) with COVID-19: a multicentre, European, observational cohort study

Background: The reduced renal function has prognostic significance in COVID-19 and it has been linked to mortality in the general population. Reduced renal function is prevalent in older age and thus we set out to better understand its effect on mortality. Methods: Patient clinical and demographic data was taken from the COVID-19 in Older People (COPE) study during two periods (February–June 2020 and October 2020–March 2021, respectively). Kidney function on admission was measured using estimated glomerular filtration rate (eGFR). The primary outcomes were time to mortality and 28-day mortality. Secondary outcome was length of hospital stay. Data were analysed with multilevel Cox proportional hazards regression, and multilevel logistic regression and adjusted for individual patient clinical and demographic characteristics. Results: One thousand eight hundred two patients (55.0% male; median [IQR] 80 [73–86] years) were included in the study. 28-day mortality was 42.3% (n = 742). 48% (n = 801) had evidence of renal impairment on admission. Using a time-to-event analysis, reduced renal function was associated with increased in-hospital mortality (compared to eGFR ≥ 60 [Stage 1&2]): eGFR 45–59 [Stage 3a] aHR = 1.26 (95%CI 1.02–1.55); eGFR 30–44 [Stage 3b] aHR = 1.41 (95%CI 1.14–1.73); eGFR 1–29 [Stage 4&5] aHR = 1.42 (95%CI 1.13–1.80). In the co-primary outcome of 28-day mortality, mortality was associated with: Stage 3a adjusted odds ratio (aOR) = 1.18 (95%CI 0.88–1.58), Stage 3b aOR = 1.40 (95%CI 1.03–1.89); and Stage 4&5 aOR = 1.65 (95%CI 1.16–2.35). Conclusion: eGFR on admission is a good independent predictor of mortality in hospitalised older patients with COVID-19 population. We found evidence of a dose-response between reduced renal function and increased mortality

Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

International audiencePurpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome