Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Does Unprecedented ICU Capacity Strain, As Experienced During the COVID-19 Pandemic, Impact Patient Outcome?

OBJECTIVES: To determine whether patients admitted to an ICU during times of unprecedented ICU capacity strain, during the COVID-19 pandemic in the United Kingdom, experienced a higher risk of death. DESIGN: Multicenter, observational cohort study using routine clinical audit data. SETTING: Adult general ICUs participating the Intensive Care National Audit & Research Centre Case Mix Programme in England, Wales, and Northern Ireland. PATIENTS: One-hundred thirty-thousand six-hundred eighty-nine patients admitted to 210 adult general ICUs in 207 hospitals. INTERVENTIONS: Multilevel, mixed effects, logistic regression models were used to examine the relationship between levels of ICU capacity strain on the day of admission (typical low, typical, typical high, pandemic high, and pandemic extreme) and risk-adjusted hospital mortality. MEASUREMENTS AND MAIN RESULTS: In adjusted analyses, compared with patients admitted during periods of typical ICU capacity strain, we found that COVID-19 patients admitted during periods of pandemic high or pandemic extreme ICU capacity strain during the first wave had no difference in hospital mortality, whereas those admitted during the pandemic high or pandemic extreme ICU capacity strain in the second wave had a 17% (odds ratio [OR], 1.17; 95% CI, 1.05-1.30) and 15% (OR, 1.15; 95% CI, 1.00-1.31) higher odds of hospital mortality, respectively. For non-COVID-19 patients, there was little difference in trend between waves, with those admitted during periods of pandemic high and pandemic extreme ICU capacity strain having 16% (OR, 1.16; 95% CI, 1.08-1.25) and 30% (OR, 1.30; 95% CI, 1.14-1.48) higher overall odds of acute hospital mortality, respectively. CONCLUSIONS: For patients admitted to ICU during the pandemic, unprecedented levels of ICU capacity strain were significantly associated with higher acute hospital mortality, after accounting for differences in baseline characteristics. Further study into possible differences in the provision of care and outcome for COVID-19 and non-COVID-19 patients is needed.

Impact of the COVID-19 pandemic on in-hospital cardiac arrests in the UK.

AIMS: To compare in-hospital cardiac arrest (IHCA) rates and patient outcomes during the first COVID-19 wave in the United Kingdom (UK) in 2020 with the same period in previous years. METHODS: A retrospective, multicentre cohort study of 154 UK hospitals that participate in the National Cardiac Arrest Audit and have intensive care units participating in the Case Mix Programme national audit of intensive care. Hospital burden of COVID-19 was defined by the number of patients with confirmed SARS-CoV2 infection admitted to critical care per 10,000 hospital admissions. RESULTS: 16,474 patients with IHCA where a resuscitation team attended were included. Patients admitted to hospital during 2020 were younger, more often male, and of non-white ethnicity compared with 2016-2019. A decreasing trend in IHCA rates between 2016 and 2019 was reversed in 2020. Hospitals with higher burden of COVID-19 had the greatest difference in IHCA rates (21.8 per 10,000 admissions in April 2020 vs 14.9 per 10,000 in April 2019). The proportions of patients achieving ROSC ≥ 20 min and surviving to hospital discharge were lower in 2020 compared with 2016-19 (46.2% vs 51.2%; and 21.9% vs 22.9%, respectively). Among patients with IHCA, higher hospital burden of COVID-19 was associated with reduced survival to hospital discharge (OR = 0.95; 95% CI 0.93 to 0.98; p < 0.001). CONCLUSIONS: In comparison with 2016-2019, the first COVID-19 wave in 2020 was associated with a higher rate of IHCA and decreased survival among patients attended by resuscitation teams. These changes were greatest in hospitals with the highest COVID-19 burden.

Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.

The Ties That Cope? Reshaping Social Connections in Response to Pandemic Distress

The COVID-19 pandemic introduced unprecedented challenges for individuals in organizations to maintain their interpersonal connections, which are critical for resource exchange. Because prior research has focused on how networks gradually evolve over time, there is little insight into how an exogenous shock, such as the pandemic, would reshape informal ties among colleagues that comprise their social networks. Drawing upon the optimal matching theory of social support, we develop a psychological perspective on how individuals recalibrate their social ties to enable coping with the uncertainty and anxiety introduced by the pandemic shock. We test our theory using a three-wave network data set from a sample of colocated, full-time MBA students before and after the onset of the pandemic. Following the onset of the pandemic, we found there was an overall reduction in the maintenance of advice ties. We also found that emotional exhaustion exacerbated this effect, and when emotional exhaustion was high, racially homophilous advice ties were just as likely to be dropped as heterophilous advice ties. We also found, unexpectedly, that COVID-19 reduced the maintenance of friendship ties, perhaps because social distancing reduced emotional support opportunities. Thoughts of anticipated inclusion mitigated this negative effect, particularly for racially heterophilous friendships. Individuals in organizations have psychological agency for reordering their social networks to respond to demands created by existential crises.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions: Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures: The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results: Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.

Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study.

OBJECTIVE: To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults. DESIGN: Self-controlled case series study using national data on covid-19 vaccination and hospital admissions. SETTING: Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom's health service (NHS). PARTICIPANTS: 29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study. MAIN OUTCOME MEASURES: The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events. RESULTS: The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test. CONCLUSION: Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.

Realising the full potential of data-enabled trials in the UK: a call for action.

RATIONALE: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. APPROACH: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. REFLECTION: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. DISCUSSION: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Prognostic Factors for 30-Day Mortality in Critically Ill Patients With Coronavirus Disease 2019: An Observational Cohort Study.

OBJECTIVES: To identify characteristics that predict 30-day mortality among patients critically ill with coronavirus disease 2019 in England, Wales, and Northern Ireland. DESIGN: Observational cohort study. SETTING: A total of 258 adult critical care units. PATIENTS: A total of 10,362 patients with confirmed coronavirus disease 2019 with a start of critical care between March 1, 2020, and June 22, 2020, of whom 9,990 were eligible (excluding patients with a duration of critical care less than 24 hr or missing core variables). MEASUREMENTS AND MAIN RESULTS: The main outcome measure was time to death within 30 days of the start of critical care. Of 9,990 eligible patients (median age 60 yr, 70% male), 3,933 died within 30 days of the start of critical care. As of July 22, 2020, 189 patients were still receiving critical care and a further 446 were still in acute hospital. Data were missing for between 0.1% and 7.2% of patients across prognostic factors. We imputed missing data ten-fold, using fully conditional specification and continuous variables were modeled using restricted cubic splines. Associations between the candidate prognostic factors and time to death within 30 days of the start of critical care were determined after adjustment for multiple variables with Cox proportional hazards modeling. Significant associations were identified for age, ethnicity, deprivation, body mass index, prior dependency, immunocompromise, lowest systolic blood pressure, highest heart rate, highest respiratory rate, Pao2/Fio2 ratio (and interaction with mechanical ventilation), highest blood lactate concentration, highest serum urea, and lowest platelet count over the first 24 hours of critical care. Nonsignificant associations were found for sex, sedation, highest temperature, and lowest hemoglobin concentration. CONCLUSIONS: We identified patient characteristics that predict an increased likelihood of death within 30 days of the start of critical care for patients with coronavirus disease 2019. These findings may support development of a prediction model for benchmarking critical care providers.

Trends in Intensive Care for Patients with COVID-19 in England, Wales, and Northern Ireland.

Rationale: By describing trends in intensive care for patients with coronavirus disease (COVID-19) we aim to support clinical learning, service planning, and hypothesis generation.Objectives: To describe variation in ICU admission rates over time and by geography during the first wave of the epidemic in England, Wales, and Northern Ireland; to describe trends in patient characteristics on admission to ICU, first-24-hours physiology in ICU, processes of care in ICU and patient outcomes; and to explore deviations in trends during the peak period.Methods: A cohort of 10,741 patients with COVID-19 in the Case Mix Program national clinical audit from February 1 to July 31, 2020, was used. Analyses were stratified by time period (prepeak, peak, and postpeak periods) and geographical region. Logistic regression was used to estimate adjusted differences in 28-day in-hospital mortality between periods.Measurements and Main Results: Admissions to ICUs peaked almost simultaneously across regions but varied 4.6-fold in magnitude. Compared with patients admitted in the prepeak period, patients admitted in the postpeak period were slightly younger but with higher degrees of dependency and comorbidity on admission to ICUs and more deranged first-24-hours physiology. Despite this, receipt of invasive ventilation and renal replacement therapy decreased, and adjusted 28-day in-hospital mortality was reduced by 11.8% (95% confidence interval, 8.7%-15.0%). Many variables exhibited u-shaped or n-shaped curves during the peak.Conclusions: The population of patients with COVID-19 admitted to ICUs, and the processes of care in ICUs, changed over the first wave of the epidemic. After adjustment for important risk factors, there was a substantial improvement in patient outcomes.

Critical care outcomes, for the first 200 patients with confirmed COVID-19, in England, Wales and Northern Ireland: A report from the ICNARC Case Mix Programme.

BACKGROUND: Early in a pandemic, outcomes are biased towards patients with shorter durations of critical illness. We describe 60-day outcomes for patients critically ill with confirmed COVID-19 and explore the potential bias in the weekly reported data by ICNARC. METHODS: First 200 consecutive patients with confirmed COVID-19, admitted for critical care in England, Wales and Northern Ireland, followed-up for a minimum of 60 days from admission. Outcomes included survival and duration of critical care, receipt/duration of organ support in critical care and hospital survival. RESULTS: Mean age was 62.6 years, 70.5% were male, 52.0% were white, 39.2% obese and 9.0% had serious comorbidities. Median APACHE II score was 16 (IQR 12, 19). After 60 days, 83 (41.5%) patients had been discharged from hospital, 15 (7.5%) had been discharged from critical care but remained in hospital, 1 (0.5%) was still receiving critical care, 90 (45.0%) had died while receiving critical care and 11 (5.5%) had died in hospital after discharge from critical care. Median duration of critical care was 14.0 days (IQR 6.1, 23.0) for survivors and 10.0 days (IQR 5.0, 16.0) for non-survivors of critical care. Overall, 158 (79.0%) patients received advanced respiratory support for a median of 13 (IQR 8, 20) calendar days. Compared with weekly reports during the pandemic, critical care mortality started higher than but then decreased below that of the first 200 consecutive patients. Duration of critical care, for both survivors and non-survivors increased over time; however, both were still lower than those for the first 200 consecutive patients. Receipt and duration of organ support increased to values similar to those for the first 200 consecutive patients. CONCLUSION: COVID-19 in critical care has high mortality and places a large burden on resources. Analysis of preliminary data with limited follow-up should be interpreted with caution, particularly for future planning in a pandemic.

COVID-19 in critical care: epidemiology of the first epidemic wave across England, Wales and Northern Ireland.

PURPOSE: To describe critical care patients with COVID-19 across England, Wales and Northern Ireland and compare them with a historic cohort of patients with other viral pneumonias (non-COVID-19) and with international cohorts of COVID-19. METHODS: Extracted data on patient characteristics, acute illness severity, organ support and outcomes from the Case Mix Programme, the national clinical audit for adult critical care, for a prospective cohort of patients with COVID-19 (February to August 2020) are compared with a recent retrospective cohort of patients with other viral pneumonias (non-COVID-19) (2017-2019) and with other international cohorts of critical care patients with COVID-19, the latter identified from published reports. RESULTS: 10,834 patients with COVID-19 (70.1% male, median age 60 years, 32.6% non-white ethnicity, 39.4% obese, 8.2% at least one serious comorbidity) were admitted across 289 critical care units. Of these, 36.9% had a PaO2/FiO2 ratio of ≤ 13.3 kPa (≤ 100 mmHg) consistent with severe ARDS and 72% received invasive ventilation. Acute hospital mortality was 42%, higher than for 5782 critical care patients with other viral pneumonias (non-COVID-19) (24.7%), and most COVID-19 deaths (88.7%) occurred before 30 days. Meaningful international comparisons were limited due to lack of standardised reporting. CONCLUSION: Critical care patients with COVID-19 were disproportionately non-white, from more deprived areas and more likely to be male and obese. Conventional severity scoring appeared not to adequately reflect their acute severity, with the distribution across PaO2/FiO2 ratio categories indicating acutely severe respiratory disease. Critical care patients with COVID-19 experience high mortality and place a great burden on critical care services.

Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people.

BACKGROUND: There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission. METHODS: This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20-99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care. FINDINGS: Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group. INTERPRETATION: ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.