Outputs from the ISARIC4C consortium

SARS-CoV-2 antibody responses

ISARIC4C have, in this study shown discernible differences in the humoral immune responses between males and females. These differences associate with age as well as with resultant disease severity. The SARS-CoV-2 pandemic enables the analysis of ...

Adeno-associated virus 2 infection in children with non-A-E hepatitis

ISARIC4C researchers found the link between adeno-associated virus 2 (AAV2) and acute hepatitis of unknown cause in children. This publication in Nature is the first peer-reviewed and detailed investigation of this worldwide outbreak. At the heigh...

Antibody responses in dried blood spots

There is good agreement between the neutralising antibody (nAb) responses measured in eluted DBS and paired sera. This emerged from this study by ISARIC4C, supporting the use of filter paper as a viable sample collection method to study n(Ab) resp...

Genetic Variants underlying Critical COVID-19

ISARIC4C researchers and the GenOMICC team have previously shown that genetics can help us to choose which drugs might be effective in treating critically ill patients, when they discovered a genetic clue that pointed to a specific treatment for C...

Pediatric COVID-19 Severity

Measurement of COVID-19 severity in children is key to determine the implications associated with the pandemic. The results of this study highlighted the importance of considering different age groups when assessing disease severity in COVID-19. I...

Recovery from COVID-19 critical illness

Fatigue may be less severe in patients who have recovered from Covid-19 than after other illness. ISARIC4C carried out a study to compare the prevalence and severity of fatigue in 92 Covid-19 versus 240 non-Covid-19 critical illness survivors. The...

Genomic investigations of unexplained acute hepatitis in children

ISARIC4C researchers worked closely with researchers led by Prof Judith Breuer at Great Ormond Street hospital and University College London. Samples from 28 children with hepatitis were tested, five of whom required liver transplants. High levels...

Co-Infection with influenza virus is associated with worse outcomes in hospitalised Covid patients

SAGE minutes This analysis provides a clear answer to a simple question: what is the effect of co-infection with common viruses on top of Covid? We compared outcomes across people who tested positive for three different viruses (influenza (flu) v...

Sharing samples and data

ISARIC4C was designed from the outset as a foundation for the UK outbreak response, supporting researchers across the country. The 4C consortium has: Responded to clinical 120 data requests, providing data to 100 collaborators Shipped out a...

Impacting Policy

ISARIC4C Tier 0/CO-CIN fed data dynamically through the Outbreak Data Analysis Platform (ODAP) to Public Health Scotland, Public Health England, SPI-M, NERVTAG and SAGE. SPI-M have been highly productive and published several analysis that informe...

Risk prediction: the 4C Mortality Score

Using data from 57, 824 hospital admissions, we developed and validated an easy-to-use risk stratification score based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility t...

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Suppression of virus replication in COVID-19 patients

Human Leukocyte Antigen E (HLA-E) restricted T-cells could contribute to the control of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection alongside classical T cells. According to this study, ISARIC4C described five peptides f...

Characterisation of hospitalised cases of COVID-19

Within weeks of being funded, we produced the largest study anywhere in the world of COVID-19 cases, enabling us to produce the most accurate risk prediction models for the UK population. These will continue to improve. The first one shows that ob...

Genetic mechanisms of severe Covid-19

In collaboration with the ISARIC GenOMICC study we discovered multiple genes that underlie critical illness in Covid-19, including several that led directly to potential therapeutic targets. In 2244 Covid cases, we compared severely ill patients ...

Clinical characterisation of Covid-19 in children

We have comprehensively characterised the burden and patterns of disease in children in the UK, demonstrating that life-threatening disease in otherwise healthy children is extremely rare. This had direct impact on public health policy in the UK a...

Characterisation of in-hospital complications associated with COVID-19

As well as death, severe COVID-19 disease has effects on many different organ systems. In this study, published in The Lancet, we characterised the burden of complications and organ injury in 73,197 patients admitted to hospital between January an...

UK Paediatric COVID-19 cases in the first and second pandemic wave

The data from paediatric patients in the ISARIC4C study were used to help inform SAGE for the vaccination policy in children and young people earlier in 2022. Even though there was a change in the viral variant, a relaxation of shielding, and a re...

WHO guidelines on the use of chest imaging in COVID-19

The ISARIC-CCP UK study has aided in the creation of the 2022 World Health Organisation (WHO) guidelines for the use of chest imaging in COVID-19. These guidelines state that “for patients with suspected or confirmed COVID-19, not currently hospit...

Using a double binding antigen assay to detect and measure SARS-CoV-2 antibodies

Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based co...

Treating COVID-19 patients with dexamethasone and remdesivir prevents neurological complications

Preventing the development of neurological complications after severe COVID-19 infections remains an important aim for doctors. Data from the ISARIC4C study group showed that individuals who go on to have neurological issues after being hospitalis...

Circulating histones play a central role in COVID-19-associated coagulopathy and mortality

COVID-19 has highlighted the lethal consequences of immunothrombosis; i.e. the cross-talk between coagulation, inflammation and the innate immune system. These patients have significant immune cell death, which can release pro-coagulant and cytoto...

Hospital acquired COVID-19 in England during the first wave of the pandemic

Using data from the ISARIC4C UK COVID-19 Clinical Information Network study, this study identified that 1 in 5 hospitalised patients in England during the first wave of the pandemic caught the virus while hospitalised for other causes. However, th...

Long Covid in adults discharged from UK hospitals after Covid-19

It is emerging that long-term symptoms are often present in people who have had acute Covid-19 disease. We found that over half of patients reported not feeling fully recovered several months after onset of Covid-19 symptoms. The symptoms reported...

Detecting SARS-CoV-2 by non-invasive means

Finding non-invasive methods to detect the SARS-CoV-2 virus has been essential for rapid self-testing during the pandemic. This study compared gingival crevicular fluid (GCF), taken by swabbing the gums, to blood samples from patients in the ISARI...

Understanding the Omicron variant and how it responds to vaccination

The Omicron variant of the SARS-CoV-2 virus spread rapidly, even in those who had been vaccinated against it. This study examined the different DNA sequence of this viral variant to determine mutations in the virus from patient blood samples from ...

Tissue proteomic analysis identifies mechanisms and stages of immunopathology in fatal COVID-19

Peripheral blood inflammatory profiles are increasingly well characterised in Covid-19 but knowledge of the host response within inflamed tissues is lacking. Post-mortem lung and spleen whole-tissue proteomics identified differentially abundant pr...

Evaluation of effectiveness of remdesivir in treating severe COVID-19

Adults with severe COVID-19 treated with remdesivir were compared with propensity-score matched control, identified from the ISARIC-CCP UK study. Remdesivir patients were matched to controls according to baseline underlying 14-day mortality risk. ...

Distinct clinical symptom patterns in patients hospitalised with COVID-19

Although the most common symptoms of COVID-19 tend to be fever, cough, and difficulty breathing, many other symptoms have been reported, including fatigue, confusion, diarrhoea, and vomiting. Using the data from 59,011 patients in the ISARI4C stud...

Vitamin D insufficiency in COVID-19 and influenza A

Vitamin D deficiency/insufficiency was present in the majority of hospitalised patients with Covid-19 (ISARIC4C study) and influenza A (MOSAIC study, 2009-10 H1N1 pandemic), correlated with severity and persisted in non-selected critical illness s...

Non-steroidal anti-inflammatory drug use and outcomes of COVID-19

Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheuma...

Role of blood cytokines IL-6 and GM-CSF in severe COVID-19

We have identified new biomarkers of inflammation that both reveal the severity of COVID-19 and set it apart from severe influenza. Many inflammatory cytokines were found in greater numbers in severe COVID-19 and that these levels generally indica...

T cells target many different parts of the virus

) This study by Yanchung Peng, Alex Mentzer, Tao Dong and colleagues reveals that the immune system responds to many different parts of the SARS-CoV-2 virus. This will influence vaccine design, which often focuses only on the most prominent parts...

Setting Serology Standards

Setting the standard ISARIC 4C defined the international reference standard for SARS-CoV-2 serology by providing the first samples to the National Institute for Biological Standards and Control (NIBSC) from COVID-19 cases. These were used to make...

Viral spike variants evading antibody-mediated immunity

We showed that the N439K viral mutation has enhanced binding affinity to the ACE2 receptor and that this variant cause infections with similar clinical outcomes compared to the wild type. This mutation is resistant against neutralising monoclonal ...

Impact of ethnicity

We have carefully studied the effect of ethnicity on outcomes in hospitalised patients, revealing the effect of comorbidities in mediating part of the increased susceptibility in some ethic groups.

Adeno-associated virus 2 infection in children with non-A-E hepatitis

An outbreak of acute hepatitis of unknown aetiology in children was first reported in Scotland in April 2022. We carried out a detailed investigation of nine cases and 58 control subjects. Using next-generation sequencing and real-time polymerase ...

SARS-CoV-2 surface and air contamination in a healthcare setting

We have explored the mechanisms of viral transmission. Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus highlighted the potential risk from surface a...

Supporting vaccine development

At the start of the pandemic, ISARIC4C was able to provide convalescent samples of PCR-positive hospitalised patients with COVID-19 to characterise the immunological properties of COVID-19. This was essential to the development of the viral vector...

ICECAP autopsy study

ISARIC 4C resources and consortium partners supported the COVID-19 post-mortem case series. This is one of several pieces of evidence that changes the model of COVID pathogenesis, supporting a primary role for the host immune system in causing fat...

Adverse outcomes in COVID-19 patients with underlying respiratory conditions

Characterisation of 75 463 hospitalised COVID-19 patients from 258 participating health-care facilities showed that underlying respiratory symptoms is common and patients with asthma were more likely, and those with chronic pulmonary disease less ...

Co-Infections, Secondary Infections, and Antimicrobial Usage

We investigated the frequency and microbiological details of bacterial co-infection and secondary infection, in addition to antimicrobial usage in 48,902 patients hsopitalised with COVID-19 during the first pandemic wave. We found that Covid-19 re...

COVID-19 and Cancer

The ISARIC4C investigators collaborated with Prof Carlo Palmieri and team to characterise the first 1,797 hospitalised patients with cancer and COVID-19. From here a new study was launched to assess the impact of COVID-19 on people with cancer: T...

Detection of antibodies to determine population exposure

ISARIC4C provided support to this study looking at population exposure in the beginning of the outbreak showing that it is likely that SARS-CoV-2 began circulating in Scotland in late February 2020 and potentially earlier.

Developing methods of sequencing the virus

Sequencing the viral genome as the outbreak progresses is important, particularly the identification of new variants and to identify whether any changes in the genome will impair clinical testing. Using the MinION/GridIONS platform, we developed a...

Vulnerability of Down's syndrome (DS) patients to severe COVID-19

Providing data and support to the Trisomy 21 Society, a study was conducted to determine if health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. Whils...

ISARIC4C within the global ISARIC-network

An alternate weekly data share is made with global ISARIC CCP partners in 42 countries and a summary report is posted on medRxiv, the global health network (TGHN.org) and WHO. CO-CIN has contributed 82% of global data reported. Selected publicati...

Modelling the association of tiered restrictions with COVID-19 deaths and hospital admissions

To look at the impact of tiered restrictions, the team fitted a mathematical model of transmission to data on hospital admissions. Results showed that lockdown measures outperformed less stringent restrictions in reducing cumulative deaths.

Multi-model forecasts to inform the response to COVID-19 in the UK

Groups of multi-model forecasts can inform the policy response to the Covid-19 pandemic by assessing future resource needs and expected population impact of morbidity and mortality.

Testing the tests

We proposed and established a Diagnostic Evaluation Platform at the University of Oxford (led by Dr Alex Mentzer) which is already being used to provide evidence to the UK government about the performance of new diagnostic and antibody tests. This...

New immune biomarkers for COVID-19

This study looked at a specific immune process in the body, known as the complement system. This mechanism allows microbes and damaged cells to be removed from the body, attacks pathogens, and promotes inflammation. This system is more active in p...

Outcomes of COVID-19 hospitalisation among patients with HIV

Providing data and support to the British HIV Association, presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the UK, were compared. HIV-positive status was associated...

Outcomes of hospitalised COVID-19 patients with interstitial lung disease

We completed an international multicentre audit of patients with prior diagnosis of Interstitial Lung Diseases (ILD) admitted to hospital with COVID-19. We showed that these patients are at increased risk of death, particularly those with poor lun...

Pulmonary Microthrombosis and Vasculitis in Life-Threatening Respiratory Virus Diseases

This study, with support and resources provided by ISARIC4C, found evidence of thrombosis present in adults with fatal influenza and SARS, with vasculitis also reported.

Symptom clusters

Because of the large scale of the ISARIC-4C study, we were able to detect robust groupings of patients with different patterns of symptoms. We found four patterns that are strikingly differnet from the core symptom groups: gastro-intestinal disea...

Nuclear magnetic resonance signals in urine

Normalization to account for variation in urinary dilution is crucial for interpretation of urine metabolic profiles. Probabilistic quotient normalization (PQN) is used routinely in metabolomics but is sensitive to systematic variation shared acro...

Using imaging in COVID-19 -- UK National COVID-19 Chest Imaging Database

The National COVID-19 Chest Imaging Database (NCCID) is a repository of chest radiographs, CT and MRI images and clinical data from COVID-19 patients across the UK, to support research and development of AI technology and give insight into COVID-1...

Viral RNA found in blood is not infectious

Laboratory diagnosis of SARS-CoV-2 infection uses PCR to detect viral RNA (vRNA) in respiratory samples. While SARS-CoV-2 RNA has been detected in other sample types, there is very little understanding about its clinical or laboratory significance...

Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study.

Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race.

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.

To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal out...

Importance of patient bed pathways and length of stay differences in predicting COVID-19 hospital bed occupancy in England.

Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients betwe...

Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19.

Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death.

Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK.

Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in h...

Clinical features and prognostic factors in Covid-19: A prospective cohort study.

Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies.

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study.

No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and iden...

Clonal hematopoiesis is not significantly associated with COVID-19 disease severity.

A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.

COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom’s re...

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study.

The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms.

Cycle threshold values are inversely associated with poorer outcomes in hospitalized patients with COVID-19: a prospective, observational cohort study conducted at a UK tertiary hospital.

This single-centre observational study demonstrated that lower cycle threshold (Ct) values (indicating higher viral loads) on admission to hospital were associated with poorer outcomes in unvaccinated, hospitalized patients with coronavirus diseas...

A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75.

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to facilitate escape from natural and vaccine-indu...

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study.

Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions.

Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publicati...

Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study.

A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or...

The COVID-19 pandemic and global environmental change: Emerging research needs.

The outbreak of COVID-19 raised numerous questions on the interactions between the occurrence of new infections, the environment, climate and health. The European Union requested the H2020 HERA project which aims at setting priorities in research ...

Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19.

The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This ...

Fitting to the UK COVID-19 outbreak, short-term forecasts and estimating the reproductive number.

The COVID-19 pandemic has brought to the fore the need for policy makers to receive timely and ongoing scientific guidance in response to this recently emerged human infectious disease. Fitting mathematical models of infectious disease transmissio...

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2.

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance comm...

Hospital-acquired SARS-CoV-2 infection in the UK's first COVID-19 pandemic wave.

In data presented to SAGE early in 2020, but published here a year later, we were the first to show the impact of in-hospital acquisition of SARS-CoV2, leading to nationwide change in practice.

Hospital admission for symptomatic COVID-19 and impact of vaccination: analysis of linked data from the Coronavirus Clinical Information Network and the National Immunisation Management Service.

We characterise the hospitalised vaccinated population and identify the effect of the relationship between vaccination status and immunocompetence on hospital mortality using the prospective observational cohort recruited from the ISARIC4C Tier Ze...

Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 human challenge model that enables controlled i...

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognit...

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and sett...

Estimating distribution of length of stay in a multi-state model conditional on the pathway, with an application to patients hospitalised with Covid-19.

Multi-state models are used to describe how individuals transition through different states over time. The distribution of the time spent in different states, referred to as ‘length of stay’, is often of interest. Methods for estimating expected l...

Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.

This study sought to establish the long-term effects of Covid-19 following hospitalisation.

Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.

Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we perfor...

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.

Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisati...

Analysis of SARS-CoV-2 in Nasopharyngeal Samples from Patients with COVID-19 Illustrates Population Variation and Diverse Phenotypes, Placing the Growth Properties of Variants of Concern in Context with Other Lineages.

New variants of SARS-CoV-2 are continuing to emerge and dominate the global sequence landscapes. Several variants have been labeled variants of concern (VOCs) because they may have a transmission advantage, increased risk of morbidity and/or morta...

Towards nationally curated data archives for clinical radiology image analysis at scale: Learnings from national data collection in response to a pandemic.

The prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for...

Endomembrane targeting of human OAS1 p46 augments antiviral activity.

Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shiel...

Obesity, Ethnicity, and Risk of Critical Care, Mechanical Ventilation, and Mortality in Patients Admitted to Hospital with COVID-19: Analysis of the ISARIC CCP-UK Cohort.

The aim of this study was to investigate the association of obesity with in-hospital coronavirus disease 2019 (COVID-19) outcomes in different ethnic groups.

Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort.

Although age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched.

Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

We demonstrated a change in the susceptibility of SARS-CoV-2 to protective antibodies.

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.

We showed that the omicron variant escaped from pre-existing antibody-mediated immunity.

Potent cross-reactive antibodies following Omicron breakthrough in vaccinees.

Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine...

Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study.

Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunoc...

Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus.

Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repert...

COVID-19 pneumothorax in the UK: a prospective observational study using the ISARIC WHO clinical characterisation protocol.

This study examined the incidence and clinical features of pneuomothorax in patients with Covid-19.

Pregnancy and neonatal outcomes of COVID-19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries.

Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from...

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study.

To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection.

A prenylated dsRNA sensor protects against severe COVID-19.

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severit...

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission.

Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World He...

Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol.

To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19.

Remdesivir Statistical Analysis Plan

The Remdesivir Statistical Analysis Plan was approved on 16 December 2020.

SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus.

We demonstrate that viral RNA in blood is not infectious.

SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.

Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered ‘aerosol-generating procedures’ in the treatment of COVID-19.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following ho...

Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection: protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales.

SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We a...

Analysis of SARS-CoV-2 known and novel subgenomic mRNAs in cell culture, animal model, and clinical samples using LeTRS, a bioinformatic tool to identify unique sequence identifiers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a complex strategy for the transcription of viral subgenomic mRNAs (sgmRNAs), which are targets for nucleic acid diagnostics. Each of these sgmRNAs has a unique 5’ sequence, the lead...

Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19: An observational cohort.

There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an ...

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern.

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we ...

Viral Coinfections in Hospitalized Coronavirus Disease 2019 Patients Recruited to the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK Study.

We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity.