Ethnic inequalities in COVID-19 infection, hospitalisation, intensive care admission, and death: a global systematic review and meta-analysis of over 200 million study participants.

Background: COVID-19 has exacerbated existing ethnic inequalities in health. Little is known about whether inequalities in severe disease and deaths, observed globally among minoritised ethnic groups, relates to greater infection risk, poorer prognosis, or both. We analysed global data on COVID-19 clinical outcomes examining inequalities between people from minoritised ethnic groups compared to the ethnic majority group. Methods: Databases (MEDLINE, EMBASE, EMCARE, CINAHL, Cochrane Library) were searched from 1st December 2019 to 3rd October 2022, for studies reporting original clinical data for COVID-19 outcomes disaggregated by ethnicity: infection, hospitalisation, intensive care unit (ICU) admission, and mortality. We assessed inequalities in incidence and prognosis using random-effects meta-analyses, with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) use to assess certainty of findings. Meta-regressions explored the impact of region and time-frame (vaccine roll-out) on heterogeneity. PROSPERO: CRD42021284981. Findings: 77 studies comprising over 200,000,000 participants were included. Compared with White majority populations, we observed an increased risk of testing positive for infection for people from Black (adjusted Risk Ratio [aRR]:1.78, 95% CI:1.59-1.99, I2 = 99.1), South Asian (aRR:3.00, 95% CI:1.59-5.66, I2 = 99.1), Mixed (aRR:1.64, 95% CI:1.02-1.67, I2 = 93.2) and Other ethnic groups (aRR:1.36, 95% CI:1.01-1.82, I2 = 85.6). Black, Hispanic, and South Asian people were more likely to be seropositive. Among population-based studies, Black and Hispanic ethnic groups and Indigenous peoples had an increased risk of hospitalisation; Black, Hispanic, South Asian, East Asian and Mixed ethnic groups and Indigenous peoples had an increased risk of ICU admission. Mortality risk was increased for Hispanic, Mixed, and Indigenous groups. Smaller differences were seen for prognosis following infection. Following hospitalisation, South Asian, East Asian, Black and Mixed ethnic groups had an increased risk of ICU admission, and mortality risk was greater in Mixed ethnic groups. Certainty of evidence ranged from very low to moderate. Interpretation: Our study suggests that systematic ethnic inequalities in COVID-19 health outcomes exist, with large differences in exposure risk and some differences in prognosis following hospitalisation. Response and recovery interventions must focus on tackling drivers of ethnic inequalities which increase exposure risk and vulnerabilities to severe disease, including structural racism and racial discrimination. Funding: ESRC:ES/W000849/1.

Ethnic inequalities in COVID-19 infection, hospitalisation, intensive care admission, and death: a global systematic review and meta-analysis of over 200 million study participants

Background COVID-19 has exacerbated existing ethnic inequalities in health. Little is known about whether inequalities in severe disease and deaths, observed globally among minoritised ethnic groups, relates to greater infection risk, poorer prognosis, or both. We analysed global data on COVID-19 clinical outcomes examining inequalities between people from minoritised ethnic groups compared to the ethnic majority group. Methods Databases (MEDLINE, EMBASE, EMCARE, CINAHL, Cochrane Library) were searched from 1st December 2019 to 3rd October 2022, for studies reporting original clinical data for COVID-19 outcomes disaggregated by ethnicity: infection, hospitalisation, intensive care unit (ICU) admission, and mortality. We assessed inequalities in incidence and prognosis using random-effects meta-analyses, with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) use to assess certainty of findings. Meta-regressions explored the impact of region and time-frame (vaccine roll-out) on heterogeneity. PROSPERO: CRD42021284981. Findings 77 studies comprising over 200,000,000 participants were included. Compared with White majority populations, we observed an increased risk of testing positive for infection for people from Black (adjusted Risk Ratio [aRR]:1.78, 95% CI:1.59–1.99, I2 = 99.1), South Asian (aRR:3.00, 95% CI:1.59–5.66, I2 = 99.1), Mixed (aRR:1.64, 95% CI:1.02–1.67, I2 = 93.2) and Other ethnic groups (aRR:1.36, 95% CI:1.01–1.82, I2 = 85.6). Black, Hispanic, and South Asian people were more likely to be seropositive. Among population-based studies, Black and Hispanic ethnic groups and Indigenous peoples had an increased risk of hospitalisation;Black, Hispanic, South Asian, East Asian and Mixed ethnic groups and Indigenous peoples had an increased risk of ICU admission. Mortality risk was increased for Hispanic, Mixed, and Indigenous groups. Smaller differences were seen for prognosis following infection. Following hospitalisation, South Asian, East Asian, Black and Mixed ethnic groups had an increased risk of ICU admission, and mortality risk was greater in Mixed ethnic groups. Certainty of evidence ranged from very low to moderate. Interpretation Our study suggests that systematic ethnic inequalities in COVID-19 health outcomes exist, with large differences in exposure risk and some differences in prognosis following hospitalisation. Response and recovery interventions must focus on tackling drivers of ethnic inequalities which increase exposure risk and vulnerabilities to severe disease, including structural racism and racial discrimination. Funding 10.13039/501100000269ESRC:ES/W000849/1.

Long title: Exhaled SARS-CoV-2 RNA viral load kinetics measured by facemask sampling associates with household transmission.

OBJECTIVES: No studies have examined longitudinal patterns of naturally exhaled SARS-CoV-2 RNA viral load (VL) during acute infection. We report this using facemask sampling (FMS) and assessed the relationship between emitted RNA VL and household transmission. METHODS: Between December 2020 and February 2021, we recruited participants within 24 hours of a positive RT-qPCR on upper respiratory tract sampling (URTS) (day 0). Participants gave FMS (for 1 hour) and URTS (self-taken) on 7 occasions up to day 21. Samples were analysed by RT-qPCR (from sampling matrix strips within the mask) and symptom diaries recorded. Household transmission was assessed through reporting of positive URTS RT-qPCR in household contacts. RESULTS: Analysis of 203 FMS and 190 URTS from 34 participants showed that RNA VL peaked in the first five days following sampling. Concomitant URTS, FMS RNA VL and symptom scores however were poorly correlated, but a higher severity of reported symptoms was associated with FMS positivity up to day 5. Of 28 participants who had household contacts, 12 (43%) reported transmission. Frequency of household transmission was associated with the highest (peak) FMS RNA VL obtained (negative copies/strip: 0% household transmission; 1-1000 copies/strip: 20%; 1001 - 10,000 copies/strip: 57%; >10,000 copies/strip: 75%; p=0.048; age adjusted odds ratio of transmission per log increase in copies/strip: 4.97; 95% CI: 1.20-20.55, p=0.02) but this was not observed with peak URTS RNA VL. CONCLUSIONS: Exhaled RNA VL measured by FMS is highest in early infection, can be positive in symptomatic patients with concomitantly negative URTS and is strongly associated with household transmission.

Prevalence of long COVID-19 among healthcare workers: a systematic review and meta-analysis protocol.

INTRODUCTION: A proportion of those who survive the acute phase of COVID-19 experience prolonged symptoms, commonly known as long COVID-19. Given that healthcare workers (HCWs) face an elevated risk of acute COVID-19 compared with the general population, the global burden of long COVID-19 in HCWs is likely to be large; however, there is limited understanding of the prevalence of long COVID-19 in HCWs, or its symptoms and their clustering. This review will aim to estimate the pooled prevalence and the symptoms of long COVID-19 among HCWs infected with SARS-CoV-2 globally, and investigate differences by country, age, sex, ethnicity, vaccination status and occupation. METHODS AND ANALYSIS: A systematic review and meta-analysis will be conducted. Medline (via Ovid), CINAHL (via EBSCO), Embase (via Ovid), PsycINFO (via EBSCO), OpenGrey (grey literature) and medRxiv (preprint server) will be searched from the 31 December 2019 onward. All research studies and preprint articles reporting any primary data on the prevalence and/or the symptoms of long COVID-19 among adult HCWs will be included. Methodological quality will be assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Outcomes are anticipated to be the prevalence of long COVID-19 among HCWs around the world and trajectory of symptoms. Data synthesis will include random-effect meta-analysis for studies reporting prevalence data of long COVID-19 following SARS-CoV-2 infection among HCWs. The results will be presented with a 95% CI as an estimated effect across studies. Heterogeneity will be assessed using I² statistic. Where meta-analysis is inappropriate, a narrative synthesis of the evidence will be conducted. ETHICS AND DISSEMINATION: Ethical approval is not needed as data will be obtained from published articles. We will publish our findings in a peer-reviewed journal and disseminate the results of our review at conferences. PROSPERO REGISTRATION NUMBER: CRD42022312781.

Overstimulation of the ergoreflex-A possible mechanism to explain symptoms in long COVID.

Long COVID refers to a multitude of symptoms that persist long after SARS-CoV-2 infection. Fatigue and breathlessness are the most common symptoms of long COVID across a range of studies. They are also cardinal symptoms of chronic heart failure (CHF). In this review, we propose that fatigue and breathlessness in patients with long COVID may be explained by skeletal muscle abnormalities, in a manner similar to patients with CHF. The ergoreflex is a cardiorespiratory reflex activated by exercise, which couples ventilation and cardiovascular function to exercise intensity. At least part of the symptomatology of CHF is related to abnormal skeletal muscle and an enhanced ergoreflex, resulting in heightened sympathetic, vasoconstrictor and ventilator drives. Similarly, SARS-CoV-2 infection results in a hyperinflammatory and hypercatabolic state. This leads to reduction in skeletal muscle mass and altered function. We postulate that the ergoreflex is chronically overstimulated, resulting in fatigue and breathlessness. Exercise training preserves muscle mass and function as well as reduces ergoreflex activation; therefore may have a role in improving symptoms associated with long COVID. Should the ergoreflex be proven to be an important pathophysiological mechanism of long COVID, tailored exercise interventions should be trialed with the aim of improving both symptoms and perhaps outcomes in patients with long COVID.

The new UK SARS-CoV-2 variant and lockdown - causes and consequences.

The new variant of concern (VOC), B.1.1.7, has a distinct set of mutations in nucleotides encoding the spike (S) protein on the surface of SARS-CoV-2. SARS-CoV-2 previously accumulated mutations at a much slower rate, of 1-2 per month; the sudden appearance of a large cluster of mutations was thought to be unusual. We now suspect that VOC may have arisen from immunosuppressed individuals who shed virus for longer periods. Epidemiological analyses estimate VOC to be more infectious; this is of most concern because these estimates were calculated during periods where many regions of the UK were in high social distancing restrictions. Therefore, the previous 'tiered' system implemented in the UK was ineffective at containing VOC. The most likely reason for this is that previous restrictions, no matter how strict, still allowed for gatherings in certain places. VOC also has implications for the national vaccination programme - a higher proportion of people will need to be vaccinated with a more infectious virus. Prolongation of the second dose of vaccines to increase vaccine uptake has understandably caused concern, but is based on sound immunological principles. There is now an urgent need to monitor the effect of new variants on vaccine efficacy - marking a new chapter in the global fight against COVID-19.

Exhaled SARS-CoV-2 quantified by face-mask sampling in hospitalised patients with COVID-19.

BACKGROUND: Human to human transmission of SARS-CoV-2 is driven by the respiratory route but little is known about the pattern and quantity of virus output from exhaled breath. We have previously shown that face-mask sampling (FMS) can detect exhaled tubercle bacilli and have adapted its use to quantify exhaled SARS-CoV-2 RNA in patients admitted to hospital with Coronavirus Disease-2019 (COVID-19). METHODS: Between May and December 2020, we took two concomitant FMS and nasopharyngeal samples (NPS) over two days, starting within 24 h of a routine virus positive NPS in patients hospitalised with COVID-19, at University Hospitals of Leicester NHS Trust, UK. Participants were asked to wear a modified duckbilled facemask for 30 min, followed by a nasopharyngeal swab. Demographic, clinical, and radiological data, as well as International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) mortality and deterioration scores were obtained. Exposed masks were processed by removal, dissolution and analysis of sampling matrix strips fixed within the mask by RT-qPCR. Viral genome copy numbers were determined and results classified as Negative; Low: ≤999 copies; Medium: 1000-99,999 copies and High ≥ 100,000 copies per strip for FMS or per 100 µl for NPS. RESULTS: 102 FMS and NPS were collected from 66 routinely positive patients; median age: 61 (IQR 49 - 77), of which FMS was positive in 38% of individuals and concomitant NPS was positive in 50%. Positive FMS viral loads varied over five orders of magnitude (<10-3.3 x 106 genome copies/strip); 21 (32%) patients were asymptomatic at the time of sampling. High FMS viral load was associated with respiratory symptoms at time of sampling and shorter interval between sampling and symptom onset (FMS High: median (IQR) 2 days (2-3) vs FMS Negative: 7 days (7-10), p = 0.002). On multivariable linear regression analysis, higher FMS viral loads were associated with higher ISARIC mortality (Medium FMS vs Negative FMS gave an adjusted coefficient of 15.7, 95% CI 3.7-27.7, p = 0.01) and deterioration scores (High FMS vs Negative FMS gave an adjusted coefficient of 37.6, 95% CI 14.0 to 61.3, p = 0.002), while NPS viral loads showed no significant association. CONCLUSION: We demonstrate a simple and effective method for detecting and quantifying exhaled SARS-CoV-2 in hospitalised patients with COVID-19. Higher FMS viral loads were more likely to be associated with developing severe disease compared to NPS viral loads. Similar to NPS, FMS viral load was highest in early disease and in those with active respiratory symptoms, highlighting the potential role of FMS in understanding infectivity.

Ethnicity and clinical outcomes in COVID-19: A systematic review and meta-analysis.

BACKGROUND: Patients from ethnic minority groups are disproportionately affected by Coronavirus disease (COVID-19). We performed a systematic review and meta-analysis to explore the relationship between ethnicity and clinical outcomes in COVID-19. METHODS: Databases (MEDLINE, EMBASE, PROSPERO, Cochrane library and MedRxiv) were searched up to 31st August 2020, for studies reporting COVID-19 data disaggregated by ethnicity. Outcomes were: risk of infection; intensive therapy unit (ITU) admission and death. PROSPERO ID: 180654. FINDINGS: 18,728,893 patients from 50 studies were included; 26 were peer-reviewed; 42 were from the United States of America and 8 from the United Kingdom. Individuals from Black and Asian ethnicities had a higher risk of COVID-19 infection compared to White individuals. This was consistent in both the main analysis (pooled adjusted RR for Black: 2.02, 95% CI 1.67-2.44; pooled adjusted RR for Asian: 1.50, 95% CI 1.24-1.83) and sensitivity analyses examining peer-reviewed studies only (pooled adjusted RR for Black: 1.85, 95%CI: 1.46-2.35; pooled adjusted RR for Asian: 1.51, 95% CI 1.22-1.88). Individuals of Asian ethnicity may also be at higher risk of ITU admission (pooled adjusted RR 1.97 95% CI 1.34-2.89) (but no studies had yet been peer-reviewed) and death (pooled adjusted RR/HR 1.22 [0.99-1.50]). INTERPRETATION: Individuals of Black and Asian ethnicity are at increased risk of COVID-19 infection compared to White individuals; Asians may be at higher risk of ITU admission and death. These findings are of critical public health importance in informing interventions to reduce morbidity and mortality amongst ethnic minority groups.

COVID-19 pandemic personal development plan: A model for maximising higher specialty training.

The coronavirus disease 2019 (COVID-19) pandemic has led to multiple service delivery changes across acute care sectors in the UK. Due to increased responsibility for care of COVID-19 patients, medical trainees across all specialties might experience difficulty in achieving certain competencies for their training curriculum due to changes in learning opportunities. While there might be a tendency to perceive these changes negatively in terms of the impact on training, we think this unprecedented situation might present a unique learning opportunity. A group of geriatric medicine trainees and trainers devised an innovative, forward-thinking specific training plan based on existing Joint Royal Colleges of Physicians Training Board geriatric medicine curricula, encouraging development of a personal development plan (PDP) tailored to the pandemic. This model could be considered for all specialty training curricula, providing a proactive approach to optimising training during the pandemic. By formulating a 'pandemic PDP' early and considering methods to maximise learning, training needs can be met even in these extraordinary times.