Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

ObjectiveTo characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C).DesignProspective observational cohort study with rapid data gathering and near real time analysis.Setting260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020).Participants651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2.Main outcome measuresAdmission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C.ResultsMedian age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group.ConclusionsChildren and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive).Study registrationISRCTN66726260.

On 31 March 2022, Public Health Scotland was alerted to five children aged 3–5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.

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Summary paragraphAn outbreak of acute hepatitis of unknown aetiology in children was first reported in Scotland in April 2022.1 Cases aged <16 years have since been identified in 35 countries.2 Here we report a detailed investigation of 9 early cases and 58 control subjects. Using next-generation sequencing and real-time PCR, adeno-associated virus 2 (AAV2), was detected in the plasma of 9/9 and liver of 4/4 patients but in 0/13 sera/plasma of age-matched healthy controls, 0/12 children with adenovirus (HAdV) infection and normal liver function and 0/33 children admitted to hospital with hepatitis of other aetiology. AAV2 typically requires a coinfecting ‘helper’ virus to replicate, usually HAdV or a herpesvirus. HAdV (species C and F) and human herpesvirus 6B (HHV6B) were detected in 6/9 and 3/9 affected cases, including 3/4 and 2/4 liver biopsies, respectively. The class II HLA-DRB1*04:01 allele was identified in 8/9 cases (89%), compared with a background frequency of 15.6% in Scottish blood donors, suggestive of increased susceptibility in affected cases. Acute non-A-E paediatric hepatitis is associated with the presence of AAV2 infection, which could represent a primary pathogen or a useful biomarker of recent HAdV or HHV6B infection. Population and mechanistic studies are required to explore these findings further.