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BackgroundHand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is associated with acute neurological disease in children.This study aimed to estimate the burden of long-term sequelae and death following severe HFMD.MethodsThis systematic review and meta-analysis pooled all reports from English and Chinese databases including MEDLINE and Wangfang on outbreaks of clinically diagnosed HFMD and/or laboratory-confirmed EV-A71 with at least 7 days' follow-up published between 1st January 1966 and 19th October 2015.Two independent reviewers assessed the literature.We used a random effects meta-analysis to estimate cumulative incidence of neurological sequelae or death.Studies were assessed for methodological and reporting quality.PROSPERO registration number: 10.15124/CRD42015021981.Findings43 studies were included in the review, and 599 children from 9 studies were included in the primary analysis.Estimated cumulative incidence of death or neurological sequelae at maximum follow up was 19.8% (95% CI:10.2%, 31.3%).Heterogeneity (Iˆ2) was 88.57%, partly accounted for by year of data collection and reporting quality of studies.Incidence by acute disease severity was 0.00% (0.00, 0.00) for grade IIa; 17.0% (7.9, 28.2) for grade IIb/III; 81.6% (65.1, 94.5) for grade IV (p = 0.00) disease.ConclusionsHFMD with neurological involvement is associated with a substantial burden of long-term neurological sequelae. Grade of acute disease severity was a strong predictor of outcome.Strengths of this study include its bilingual approach and clinical applicability.Future prospective and interventional studies must use rigorous methodology to assess long-term outcomes in survivors.FundingThere was no specific funding for this study. See below for researcher funding.

COVID-19 causes immune perturbations which may persist long-term, and patients frequently report ongoing symptoms for months after recovery. We assessed immune activation at 3-12 months post hospital admission in 187 samples from 63 patients with mild, moderate or severe disease and investigated whether it associates with long COVID. At 3 months, patients with severe disease displayed persistent activation of CD4+ and CD8+ T-cells, based on expression of HLA-DR, CD38, Ki67 and granzyme B, and elevated plasma levels of IL-4, IL-7, IL-17 and TNF-α compared to mild and/or moderate patients. Plasma from severe patients at 3 months caused T-cells from healthy donors to upregulate IL-15Rα, suggesting that plasma factors in severe patients may increase T-cell responsiveness to IL-15-driven bystander activation. Patients with severe disease reported a higher number of long COVID symptoms which did not however, correlate with cellular immune activation/pro-inflammatory cytokines after adjusting for age, sex and disease severity. Our data suggests that long COVID and persistent immune activation may correlate independently with severe disease.

Background In March 2020, Covid-19 secondary to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was declared a global pandemic. Methods This retrospective observational study included patients with Covid-19, managed in a single intensive care unit (ICU). We collected data on patient characteristics, laboratory and radiological findings and ICU management. Data are reported as median (interquartile range). Binary logistic regression modelling was used to identify variables at ICU admission associated with mortality. Results 85 patients (age 57.3 years [49.4–64.2], 75.3% male) were followed up for 34 days (26–40). The commonest comorbidities were hypertension (51.8%), obesity (48.7%), and type 2 diabetes (31.8%). Covid-19 presented with shortness of breath (89.4%), fever (82.4%), and cough (81.2%), first noted 8 days (6–10) prior to ICU admission. PaO2/FiO2-ratios at ICU admission were 8.28 kPa (7.04–11.7). Bilateral infiltrates on chest X-ray, lymphopenia, and raised C-reactive protein and ferritin were typical. 81.2% received invasive mechanical ventilation (IMV). Acute kidney injury occurred in 62.4% with renal replacement therapy required in 20.0%. By the end of the follow-up period, 44.7% had died, 30.6% had been discharged from hospital, 14.1% had been discharged from ICU but remained in hospital and 10.6% remained in ICU. ICU length of stay was 14 days (9–23). Age was the only variable at admission which was associated with mortality. PaO2/FiO2-ratio, driving pressure and peak ferritin and neutrophil count over the first 72-hours of IMV all correlated with mortality. Conclusions We report the clinical characteristics, ICU practices and outcomes of a South London cohort with Covid-19, and have identified factors which correlate with mortality. By sharing our insight, we hope to further understanding of this novel disease.