COVID-19 Literature Digest – 25/06/2021 Dear all,

Please find today’s report below. PHE’s COVID-19 Literature Digest has been produced since February 2020. A selection of our previous Digests can be found here. This resource aims to highlight a small selection of recent COVID-19 papers that are relevant to UK settings, contain new data, insights or emerging trends. The Digest Team generate a report once per week (Fri). The reports include both preprints, which should be treated with caution as they are NOT peer-reviewed and may be subject to change, and also research that has been subject to peer review and wider scrutiny. The Digest is very rapidly produced and does not claim to be a perfect product; the inclusion or omission of a publication should not be viewed as an endorsement or rejection by PHE. We do not accept responsibility for the availability, reliability or content of the items included in this resource. To join our email distribution list please send a request to COVID.LitDigest@phe.gov.uk. If you are interested in papers relating to behaviour and social science please contact COVID19.behaviouralscience@phe.gov.uk to sign up to receive the PHE Behavioural Sciences Weekly Report. Best wishes, Emma Farrow, James Robinson, Kester Savage, Rachel Gledhill, Nicola Pearce-Smith, Michael Cook On behalf of the PHE COVID-19 Literature Digest Team _____________________________________________

Report for 25.06.2021 (please note that papers that have NOT been peer-reviewed are highlighted in red). Sections: Serology and immunology Vaccines Diagnostics and genomics Epidemiology and clinical - children and pregnancy Epidemiology and clinical - long-term complications / sequelae Epidemiology and clinical - risk factors Epidemiology and clinical - other Infection control / non-pharmaceutical interventions

Transmission Treatment Modelling Guidance and consensus statements (no digest) Overviews, comments and editorials (no digest) Serology and immunology

Publication Date

Title/URL Journal / Article type Digest

22.06.2021 Seroprevalence of SARS-CoV-2 among Blood Donors and Changes after Introduction of Public Health and Social Measures, London, UK

Emerg Infect Dis / Article • An analysis of blood donor samples collected in London at three time points during the pandemic, commencing 23.03.2021, using three different assays; two commercially available from Euronimmun and Abbot and a third developed in the Virus Reference Department at Public Health England • In London, ≈14% donors had evidence of infection by week 18, the highest for any region of England. • The sensitivity analysis indicates that the assay targeting the nucleoprotein identifies early infections; the assays targeting the spike protein are more reliable in picking up late infections, demonstrating the value in combining data from different serologic assays with different target proteins for determining seroprevalence. • The results also confirm transmission slowed substantially after lockdown measures were put in place, plateauing from weeks 15–16 to 18.

18.06.2021 Immunological imprinting of the antibody response in COVID-19 patients

Nat Commun / Article • Longitudinal profile of the early humoral immune response against SARS-CoV-2 in In a cohort of 37 hospitalised COVID-19 patients, to quantify pre-existing immunity to other seasonal coronaviruses, HKU1, OC43 and 229E • Whilst all patients developed antibody responses against SARS-CoV-2 antigens and specific neutralizing antibodies, findings provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

17.06.2021 One year later: SARS-CoV-2 immune response and vaccination of healthcare workers post-infection

J Infect / Letter to the editor • Study of 276 seropositive healthcare workers (HCWs) in France found that binding and neutralising antibodies persist for up to one year post-infection; data suggests vaccinating individuals who have

already been infected induces a higher level of protection than that following infection alone.

23.06.2021 Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients

N Engl J Med / Correspondence • Reports humoral response in 101 solid-organ transplant recipients in France, given three doses of the BNT162b2 (Pfizer–BioNTech) Covid-19 vaccine. • Prevalence of anti–SARS-CoV-2 antibodies was 0% before the first dose, 4% before the second dose, 40% before the third dose, and 68% four weeks after the third dose. • Among 59 patients seronegative before the third dose, 26 (44%) were seropositive 4 weeks after the third dose. • Patients who did not have an antibody response were older, had higher degree of immunosuppression, and had lower estimated glomerular filtration rate. • At time of writing, Covid-19 had not developed in any patients after receiving the three vaccine doses. No serious adverse events reported.

11.06.2021 Memory B cells targeting SARS-CoV-2 spike protein and their dependence on CD4(+) T cell help

Cell Rep / Article • Authors investigate SARS-CoV-2 spike-specific memory B cells and their dependence on CD4+ T cell help in different settings of COVID-19. • Compared with severely ill individuals, those who recovered from mild COVID-19 develop fewer but functionally superior spike-specific memory B cells. • Severe COVID-19 causes excessive activation and exhaustion of B cells. • Membrane-specific CD4+ T cells are strongly associated with spike-specific B cells.

23.06.2021 Detection of serum cross-reactive antibodies and memory response to SARS-CoV-2 in pre-pandemic and post-COVID-19 convalescent samples

J Infect Dis / Article • Research demonstrates pre-existing cross-reactive anti-SARS-CoV-2 antibodies in around 40% pre-pandemic serum samples from children and young adults, which were likely derived from infection with common endemic beta coronaviruses • The presence of cross-reactive antibodies was found to be rare in the pre-pandemic serum samples of the healthy adult volunteers • These findings may form part of the explanation for the lower susceptibility to severe disease found in children, and promoting this cross-reactive immunity may be an effective strategy against SARS-CoV-2 and future novel coronaviruses

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Vaccines

Publication Date

Title/URL Journal / Article type Digest

23.06.2021 Effectiveness of BNT162b2 and ChAdOx1 nCoV-19 COVID-19 vaccination at preventing hospitalisations in people aged at least 80 years: a test-negative, case-control study

Lancet Infect Dis / Article • UK study to determine effectiveness of one vaccine dose in reducing COVID-19-related admissions to hospital in older people (80 years or older) with many comorbidities. • Between Dec 18, 2020 - Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). • 9 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2 [Pfizer]: vaccine effectiveness was 71·4%. • Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19 [AstraZeneca]: vaccine effectiveness was 80·4%. • When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3%. • One dose of either vaccine resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years.

23.06.2021 Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study

Lancet Infect Dis / Article • In a cohort study of 10,412 older adults living in Long-Term Care Facilities across England, a first dose of BNT162b2 [Pfizer] vaccine (n=3,022) or ChAdOx1 nCoV-19 [AstraZeneca] vaccine (n=6,138) was associated with substantially reduced SARS-CoV-2 infection risk from 4 weeks to at least 7 weeks. • Preprint previously included

16.06.2021 CureVac Provides Update on Phase 2b/3 Trial of First-Generation COVID-19 Vaccine Candidate, CVnCoV

CureVac (non-peer reviewed) / Press Release

• Interim analysis of phase 2b/3 trial of COVID-19 vaccine candidate CVnCoV (CureVac); approximatively 40,000 participants in ten countries in Latin America and Europe (the HERALD study). • In the unprecedented context of at least 13 variants circulating within the study population subset assessed at this interim analysis, CVnCoV demonstrated interim vaccine efficacy of 47% against COVID-19 disease of any severity; favourable safety profile was confirmed.

18.06.2021 Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS-CoV-2

Ann Rheum Dis / Article • Study of humoral response after two doses of Pfizer vaccine in 264 patients with inflammatory rheumatic diseases (IRD) treated with immunomodulating drugs. • 227 patients (86%) mounted IgG Ab against SARS-CoV-2. Of 37 (14%) who didn't, 22/37 were treated with B cell-depleting agents. • The reported side effects of the vaccine were minor. The rheumatic disease remained stable in all patients.

Back to menu Diagnostics and genomics

Publication Date

Title/URL Journal / Article type Digest

21.06.2021 Real-time Alerting System for COVID-19 Using Wearable Data

medRxiv (non-peer reviewed) / Article

• Authors describe an open-source, scalable, real-time smartwatch-based alerting system for detection of aberrant physiological and activity signals (e.g. resting heart rate, steps) associated with early COVID-19 infection. • In a cohort of 3,246 participants, alerts were generated for pre-symptomatic and asymptomatic COVID-19 infections in 78% of cases; pre-symptomatic signals were observed a median of three days prior to symptom onset. • Examination of over 100,000 survey annotations suggests other respiratory infections as well as events not associated with COVID-19 (e.g. stress, alcohol consumption, travel) could trigger alerts, albeit at a lower mean period (1.9 days) than those observed in COVID-19 cases (4.3 days).

24.06.2021 Test, trace, isolate: evidence for declining SARS-CoV-2 PCR sensitivity in a clinical cohort

Diagn Microbiol Infect Dis / Research article

• In a cohort of 644 patients that presented with clinically suspected COVID-19 testing was carried out by real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples. • A decrease in sensitivity with decreasing disease severity was observed, as well as an increase in sensitivity in immunocompromised patients and a rapid decline of sensitivity in time post onset of symptoms, but only in outpatients. • Whilst the analytical sensitivity of PCRs generally approaches 100%, meaning tests are able to detect a single viral genome copy in the reaction volume, the clinical sensitivity may be substantially lower, with ramifications for screening, treatment and isolation measures in hospitals and the general population.

12.06.2021 Rapid COVID-19 Risk Screening by Eye-region Manifestations

ArXiv (non-peer reviewed) / Article • The authors describe a new fast method of COVID-19 rapid pre-screening which analyses eye-region images, captured by common CCD and CMOS cameras; the model is lower cost, fully self-performed, non-invasive and real-time.

• Pilot experiments demonstrate the model is usable in many surveillance scenarios, such as infrared temperature measurement device at airports and stations, or as a targeted smartphone application.

18.06.2021 Generation and transmission of inter-lineage recombinants in the SARS-CoV-2 pandemic

medRxiv (non-peer reviewed) / Article

• Presents evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. • Genomes carry single nucleotide polymorphisms and deletions characteristic of VOC B.1.1.7, but lack the full complement of lineage-defining mutations; the remainder of their genomes share contiguous genetic variation with non-B.1.1.7 viruses circulating in the same geographic area at the same time as the recombinants; this is evidence for onward transmission of a recombinant-origin virus in four instances. • Inferred genomic locations of recombination breakpoints suggest every community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage.

Back to menu Epidemiology and clinical - children and pregnancy

Publication Date

Title/URL Journal / Article type Digest

21.06.2021 Association Between Race and COVID-19 Outcomes Among 2.6 Million Children in England

JAMA Pediatr / Original Investigation • Cohort study of 2,576,353 children (0-18 years of age) from participating family practices in England [24 January - 30 November 2020]. • SARS-CoV-2 testing varied across race: White children 17.1%; Asian children 13.6%; Black children 8.3%; children of mixed or other races 12.9%. • Compared with White children, Asian children were more likely to have COVID-19 hospital admissions (adjusted odds ratio [OR] 1.62), whereas Black children (adjusted OR 1.44) and children of mixed or other races (adjusted OR 1.40) had comparable hospital admissions. • Asian children were more likely to be admitted to intensive care (adjusted OR 2.11), and Black children (adjusted OR 2.31) and

children of mixed or other races (adjusted OR 2.14) had longer hospital admissions (≥36 hours). • Ascertainment bias and residual confounding in this study should be considered before drawing any further conclusions. • Associated editorial: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2780971

22.06.2021 Report of a Confirmed SARS-CoV-2 Positive Newborn after Delivery Despite Negative SARS-CoV-2 Testing on Both Parents

AJP Rep / Case report • Case report of an infant born to an asymptomatic mother who required immediate transfer to neonatal ICU for respiratory distress. • The infant tested positive for SARS-CoV-2 by RT-PCR at 24 hours of life. This was repeated on day of life 4, which confirmed a positive diagnosis. • Both parents remained asymptomatic and tested negative for SARS-CoV-2 on two separate occasions. • This case raises the concerns of the unreliability of negative maternal COVID-19 testing and the potential of nosocomial infection within the first 24 hours of life.

Back to menu Epidemiology and clinical - long-term complications / sequelae

Publication Date

Title/URL Journal / Article type Digest

24.06.2021 Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people

Imperial College London (non-peer reviewed) / Article

• Among 508,707 REACT-2 participants, weighted prevalence of self-reported COVID-19 was 19.2%. • Of 76,155 symptomatic people post COVID-19 infection, 37.7% experienced at least one symptom and 14.8% experienced 3+ symptoms, lasting 12 weeks or more; a weighted prevalence of 5.75% and 2.22% respectively. • Of those with at least one symptom lasting 12 weeks or more, 30.5% (8,771/28,713) reported severe COVID-19 symptoms (“significant effect on my daily life”) at the time of their illness: a weighted prevalence of 1.72%. • Prevalence of persistent symptoms higher in women than men (OR: 1.51) and, conditional on reporting symptoms, risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade of life.

• Obesity, smoking or vaping, hospitalisation and deprivation were also associated with higher probability of persistent symptoms, while Asian ethnicity was associated with lower probability. • Associated press release: https://www.imperial.ac.uk/news/224853/over-million-adults-england-have-long/

21.06.2021 Recovery from Covid-19 critical illness: a secondary analysis of the ISARIC4C CCP-UK cohort study and the RECOVER trial

medRxiv (non-peer reviewed) / Article

• Secondary analysis of two prospectively collected datasets; included 92 Covid-19 patients who received invasive mechanical ventilation (IMV) and 240 patients who received IMV with non-Covid-19 illness before the pandemic. • At 3-months, prevalence (38.9% [7/18] vs. 27.1% [51/188]) and severity (median 5.5/10 vs. 5.0/10) of fatigue was similar between the Covid-19 and pre-pandemic populations respectively. • At 6-months, the prevalence (10.3% [3/29] vs. 32.5% [54/166]) and severity (median 2.0/10 vs. 5.7/10) of fatigue was less in the Covid-19 cohort. • In the total sample population, having Covid-19 was significantly associated with less severe fatigue (severity <7/10) after adjusting for age, sex, and prior comorbidity (adjusted OR 0.35).

23.06.2021 Long COVID in a prospective cohort of home-isolated patients

Nat Med / Article • Follow-up of prospective cohort study of 312 patients (247 home-isolated / 65 hospitalized) comprising 82% of total cases in Bergen during Norway's first wave. • At 6 months, 61% (189/312) had persistent symptoms. 52% (32/61) of home-isolated young adults (16–30 years) had symptoms including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). • Young, home-isolated adults with mild COVID-19 being at risk of long-lasting dyspnea / cognitive symptoms highlights importance of infection control measures like vaccination.

20.06.2021 Brain imaging before and after COVID-19 in UK Biobank

medRxiv (non-peer reviewed) / Article

• Study of 782 participants from the UK Biobank COVID-19 re-imaging study compared scans taken before infection and after recovery in 394 participants who tested positive for SARS- CoV-2 and compared them with 388 health controls. • Findings suggest significant effects of COVID-19 in the brain with a loss of grey matter in the left parahippocampal gyrus, the left lateral orbitofrontal cortex and the left insula; these results extended to the anterior cingulate cortex, supramarginal gyrus and temporal pole.

03.06.2021 Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories

Front Aging Neurosci / Systematic Review

• Systematic review (90 studies, mainly single cases and case series); studies on COVID-19 related neural damage are diverse, but limited to description of hospitalised patients with fatal outcome or severe symptoms. • Damage seen in this population indicates acute and largely irreversible dysfunction to neural regions involved in major functional networks that support normal cognitive and behavioural functioning. • Unclear whether the long-term impact will be limited to chronic evolution of acute events, whether sub-clinical pathological processes will be exacerbated, or whether novel mechanisms will emerge.

Back to menu Epidemiology and clinical – risk factors

Publication Date

Title/URL Journal / Article type Digest

21.06.2021 Clinical characteristics and risk factors associated with nosocomial COVID-19 infection in patients with hematological disorders in Japan

Int J Hematol / Article • Analyses COVID-19 mortality risk factors for 34 patients admitted to the haematology department at a hospital in Japan. • Mortality rate of all patients was 62% (21 of the 34 patients), and most of these patients had malignant malignancies; patients not yet in remission had a 10.8-fold higher risk of death than those in remission; and the group receiving chemotherapy with steroids had a shorter survival time and had an 8.3-fold higher risk of death than that receiving chemotherapy without steroids.

02.06.2021 Eosinophils and Chronic Respiratory Diseases in Hospitalized COVID-19 Patients

Front Immunol / Original Research • Retrospective analysis of persons with SARS-CoV-2 infection attending at two public hospitals in Madrid, Spain; of 2539 subjects assessed, 1396 presented an eosinophil count performed on admission, revealing eosinopenia in 376 cases (26.93%). • Eosinopenia on admission was associated with a higher risk of intensive care unit (ICU) or respiratory intensive care unit (RICU) admission (OR:2.21) but no increased risk of mortality.

15.06.2021 Impact of pre-existing heart failure on 60-day outcomes in patients hospitalized with COVID-19

Am Heart J Plus / Article • A retrospective analysis of 1331 patients who tested positive for SARS-CoV-2 between March and June 2020 identified 188 with heart failure (HF) • HF patients were found not to have a higher risk of 60-day mortality compared to patients without HF, but a higher risk for morbidity.

• HF patients were more likely to require readmission within 60 days and sustain myocardial injury as well as a need for structured hospital follow up to avoid readmission.

22.06.2021 COVID-19 fatalities by zip codes and socioeconomic indicators across various U.S. regions

Ann Med Surg (Lond) / Article • A cross-sectional study of 1,853 zip codes in 327 counties across the US, using data obtained via state/county Department of Health (DOH) and/or state/county public health department as of 23.12.2020. • A significant positive correlation was found between case-fatality ratio (CFR) and median household income. There was no significant correlation between the CFR and population density or unemployment rate • Nursing homes were heavily distributed in zip codes with high CFR and the authors recommend the targeted vaccination of zip codes with a large proportion of long-term care facilities as well as improved screening and safety guidelines for vulnerable populations

Back to menu Epidemiology and clinical – other

Publication Date

Title/URL Journal / Article type Digest

11.06.2021 Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study

Br J Anaesth / Article • From 1 January 2020 to 28 February 2021, a total of 2,666,978 patients underwent surgery in England; 28,777 (1.1%) had SARS-CoV-2 infection, suggesting current prevention and control policies are effective. • SARS-CoV-2 infection was associated with a much greater risk of death than no SARS-CoV-2 infection (21.4% vs 0.8%, respectively; OR=5.7). • Amongst patients undergoing elective surgery (n=1,857,586), 0.1% had SARS-CoV-2, of whom 7.1% died, compared with 0.1% of patients without SARS-CoV-2 (OR=25.8). • Amongst patients undergoing emergency surgery (n=582,292), 3.9% had SARS-CoV-2, of whom 25.1% died, compared with 3.4% of patients without SARS-CoV-2 (OR=5.5).

19.06.2021 Occupational differences in COVID-19 incidence, severity, and mortality in the United Kingdom: Available data and framework for analyses

Wellcome Open Res / Article • A large number of data sets are available to potentially assess occupational risks of COVID-19 incidence, severity, or mortality in UK. • Author are reviewing these under Partnership for Research in Occupational, Transport, Environmental COVID Transmission

(PROTECT) initiative; conclude none are ideal, and all have various strengths and weaknesses.

19.06.2021 Health-related quality of life issues, including symptoms, in patients with active COVID-19 or post COVID-19; a systematic literature review

Qual Life Res / Reviews • Mapping review to identify all relevant health-related quality of life (HRQoL) issues associated with COVID-19; updated Feb 2021 to include long-term consequences

22.06.2021 Retrospective analysis on the clinical characteristics of patients who were reinfected with the Corona Virus in 2019

Am J Transl Res / Article • Analysis of the medical records of 742 COVID-19 patients discharged between 20.02.2020 – 03.04.2020, including 60 (8.1%) who had been re-infected • Of the patients who were re-infected, 2 cases were mild and 58 were moderate. There were no serious cases among the re-infected patients and no statistical difference between mild cases and moderate cases in the time from initial cure to re-infection, which had a range of 15.7 days. • Nasal congestion and runny nose, lymphocyte count less than 0.93×109 cells/L, and age more than 65 years were the risk factors of re-infection in patients with COVID-19, and lymphocyte count has certain clinical value in predicting reactivation.

24.06.2021 Risk of SARS-CoV-2 infection and subsequent hospital admission and death at different time intervals since first dose of COVID-19 vaccine administration, Italy, 27 December 2020 to mid-April 2021

Eurosurveillance / Rapid communication

• Analysis of data from over 7 million recipients of at least one COVID-19 vaccine dose in Italy suggests SARS-CoV-2 infection risk subsequently decreased, reaching a 78% reduction (incidence rate ratios (IRR): 0.22) at 43–49 days post-first dose. • Hospitalisation and mortality also decreased: 89% (IRR: 0.11) and 93% (IRR: 0.07) reductions 36–42 days post-first dose.

23.06.2021 Epidemiologic Analysis of Chilblains Cohorts Before and During the COVID-19 Pandemic

JAMA Dermatol / Original Investigation

• Retrospective cohort study of patients in a health system covering approximately 4.4 million people in northern California, USA • A total of 780 chilblains cases identified from April to December 2020; COVID-19 incidence was correlated with chilblains incidence at 207 location-months (Spearman coefficient 0.18), representing 23 geographic locations. However only 3.7% (17/456) patients with chilblains tested during the pandemic were positive for SARS-CoV-2, and only 2.0% (9/456) were positive for SARS-CoV-2 within 6 weeks of the chilblains diagnosis. • Authors suggest either a causal role of COVID-19, increased care-seeking by patients with chilblains during the pandemic, or changes in behaviour during lockdown.

23.06.2021 Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support: REACT-SCOT case-control study

BMC Med / Article • Matched case-control study: the REACT-SCOT dataset was linked to the list of 212,702 individuals identified as eligible for shielding in Scotland. • Univariate rate ratio for severe COVID-19 was 3.21 in those with moderate risk conditions and 6.3 in those eligible for shielding. Highest rate was in solid organ transplant recipients (RR 13.4). • Risk of severe COVID-19 increased with number of adults in the household but decreased with the number of school-age children. • Severe COVID-19 was strongly associated with recent exposure to hospital [5 to 14 days before presentation date]: RR 12.3 overall. The population attributable risk fraction for recent exposure to hospital peaked at 50% in May 2020 and again at 65% in December 2020. • Findings suggest effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household.

Back to menu Infection control / non-pharmaceutical interventions

Publication Date

Title/URL Journal / Article type Digest

23.06.2021 Association between COVID-19 outcomes and mask mandates, adherence, and attitudes

PLoS One / Article • Findings suggest mask mandates are associated with significant decrease in new cases (-3.55 per 100K), deaths (-0.13 per 100K), and proportion of hospital admissions (-2.38 percentage points) up to 40 days after introduction at both state and county level. This corresponds to 14% of the highest recorded number of cases, 13% of deaths, and 7% of admission proportion. • Mask mandates linked to 23.4 percentage point increase in mask adherence in four diverse states. Ending of mask mandates in these states is estimated to decrease mask adherence by -3.19 percentage points and 12 per 100K (13% of the highest recorded number) of daily new cases; no significant effect on hospitalisations and deaths. • A large novel survey dataset of 847,000 responses in 69 countries suggests community mask adherence and community attitudes towards masks are associated with reduction in COVID-19 cases and deaths.

Back to menu Transmission

Publication Date

Title/URL Journal / Article type Digest

23.06.2021 Effect of Vaccination on Household Transmission of SARS-CoV-2 in England

N Engl J Med / Correspondence • Authors analyse data from the Household Transmission Evaluation Dataset (HOSTED) between 4 January and 28 February 2021; there were 960,765 household contacts of unvaccinated index patients in England, and 96,898 secondary cases of Covid-19 (10.1%). • Overall likelihood of household transmission was approximately 40 to 50% lower in households of index patients vaccinated 21 days or more before testing positive than in households of unvaccinated index patients; findings were similar for the both vaccines [Pfizer-BioNTech or Oxford-AstraZeneca]. Most vaccinated index patients in the data set (93%) had received only the first dose of vaccine. • Assessment of infection risks among household contacts according to the timing of index patient vaccination showed protective effects when the vaccine was administered at least 14 days before the positive test.

21.06.2021 Assessing the Association Between Social Gatherings and COVID-19 Risk Using Birthdays

JAMA Intern Med / Original investigation

• Cross-sectional study used administrative health care data on 2.9 million US households [1 January - 8 November 2020]. • Among households in the top decile of county COVID-19 prevalence, those with birthdays in the 2 weeks prior had 8.6 more diagnoses per 10,000 individuals compared with households without a birthday; a relative increase of 31% of county-level prevalence; an increase in COVID-19 diagnoses of 15.8 per 10,000 persons after a child birthday, and 5.8 per 10,000 among households with an adult birthday. • Findings suggest birthdays and other events which lead to small social gatherings may be an important source of SARS-CoV-2 transmission. • Associated commentary: https://www.scientificamerican.com/article/childrens-birthdays-may-have-spread-covid-infections/

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Treatment

Publication Date

Title/URL Journal / Article type Digest

21.06.2021 Evaluation of the effectiveness of remdesivir in treating severe COVID-19 using data from the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, national cohort study

medRxiv (non-peer reviewed) / Article

• Study of ISARIC WHO Clinical Characterisation Protocol study patients; 1,549 patients given remdesivir compared with 4,964 matched controls. • Fourteen-day mortality was not statistically significantly associated with treatment: 9.3% remdesivir vs. 11.9% controls (odds-ratio 0.80), adjusted for age, sex, number of key comorbidities, dexamethasone use, and diagnosis of viral pneumonia.

21.06.2021 Blood purification with CytoSorb in critically ill COVID-19 patients: A case series of 26 patients

Artif Organs / Article • A retrospective study to investigate the effectiveness of CytoSorb, a hemoadsorption therapy, as a treatment for COVID-19 patients with acute respiratory dysfunction syndrome (ARDS) admitted to intensive care between 03.04.2020 and 23.09.2020 • Study indicates that treatment with CytoSorb achieves (i) a reduction in inflammatory mediator plasma levels, which may be consistent with a rebalancing of the hyperinflammatory response, (ii) hemodynamic stabilisation accompanied by a rapid decrease in vasopressor requirements and (iii) a significant improvement in lung function/oxygenation and overall organ functions (SOFA) • 21 of the 26 patients survived and time from onset of symptoms until start of CytoSorb therapy was significantly shorter in the survivors, however, results on the early use of hemoadsorption in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) therapy, pointed towards negative effects on outcome

22.06.2021 Interventions in an Ambulatory Setting to Prevent Progression to Severe Disease in Patients With COVID-19: A Systematic Review

Ann Pharmacother / Systematic review

• Eight papers from an initial retrieval of 3818 articles were found eligible for inclusion in a systematic review of research into nine pharmacological interventions: (1) Bamlanivimab, (2) Bamlanivimab Plus Etesevimab, (3) Casirivimab plus Imdevimab (REGN-COV2), (4) Fluvoxamine, (5) Interferon (Peginterferon Lambda-1a), (6) Ivermectin, (7) Ivermectin Plus Doxycycline, (8) Nitazoxanide, (9) Sulodexide • Despite promising trials for a number of treatments, the current review demonstrates a need for larger, more robust trials to support their routine use outside of monitored clinical trials.

22.06.2021 Respiratory Physiology of Prone Positioning With and Without Inhaled Nitric Oxide Across the Coronavirus Disease 2019 Acute

Crit Care Explor / Article • Retrospective cohort study of 122 consecutively admitted patients with acute respiratory distress syndrome (ARDS) due to COVID-19,

Respiratory Distress Syndrome Severity Spectrum

treated with mechanical ventilation and prone positioning in an intensive care unit (ICU) between 11.03.2020 and 01.05.2020 • Prone positioning, which improves oxygenation across the ARDS severity spectrum, was found to have a greater relative benefit among patients with more severe disease. This treatment also confers an additive benefit in oxygenation among patients treated with inhaled nitric oxide.

Back to menu Modelling

Publication Date

Title/URL Journal / Article type Digest

18.06.2021 Community factors and excess mortality in first wave of the COVID-19 pandemic in England

Nat Commun / Article • Two-stage Bayesian spatial modelling to explore characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. • Communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. • No association found between population density or air pollution and excess mortality.

22.06.2021 Incorporating dynamic flight network in SEIR to model mobility between populations

Appl Netw Sci / Article • A modelling study, using Canadian data, to explore a modification to the SEIR model to derive inflow and outflow of exposed individuals from flight information and enable early detection of outbreaks by taking into consideration the demographic dynamics of the population • The proposed modification provides a more accurate estimation of parameters such as the population reproduction number and simulates the impact of travel restriction, enabling a better understanding of disease and evaluation of the implications of lifting restrictions

19.06.2021 Jointly Modelling Economics and Epidemiology to Support Public Policy Decisions for the COVID-19 Response: A Review of UK Studies

Pharmaco-economics / Review Article

• Rapid review of UK modelling studies seeking to integrate epidemiological and economic modelling to assess the impacts of alternative policies.

• Few UK-focussed studies have attempted so far to balance health and economic outcomes of these policies, using a joint epidemiological and economic modelling framework.

22.06.2021 Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England

Sci Transl Med / Research article • Modelling study synthesising multiple surveillance data streams into a single coherent framework and provides an overview of transmission, hospitalisation and mortality in both first and second waves of the epidemic in England. • Findings demonstrate that national lockdown in England was the only control measure to bring the reproduction number below 1 consistently and that introducing this one week earlier may have reduced deaths in the first wave from 48,600 to 25,600

18.06.2021 Mass mask-wearing notably reduces COVID-19 transmission

medRxiv (non-peer reviewed) / Article

• Modelling of 92 regions on 6 continents suggests that an entire population wearing masks in public leads to a median 25.8% reduction in the R number, with 95% of the medians between 22.2% and 30.9%. Median reduction in R associated with the wearing level observed in each region was 20.4%. • Did not find evidence that mandating mask-wearing reduces transmission. Results also suggest mask-wearing is strongly affected by factors other than mandates.

22.06.2021 Effects of COVID-19 Vaccination Timing and Risk Prioritization on Mortality Rates, United States

Emerg Infect Dis / Research letter • Mathematical model of transmission to project COVID-19 deaths over 8 months using two separate rollout commencement dates, 15.01.2021 and 15.02.2021 • The model projected the outcomes of three different prioritisation strategies, and reflects conditions in the United States as cases were surging toward a pandemic peak • The authors conclude that whilst risk-prioritisation was a valid approach for maximising the effect of the vaccine, the timing of vaccination rollout would be expected to have a greater effect on mortality rate.

20.06.2021 Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis

medRxiv (non-peer reviewed) / Article

• Modelling study examines the potential public-health impact of a range of different potential COVID-19 therapeutics, under a range of different scenarios. • Findings suggest the impact of drugs like dexamethasone - usually delivered to the most critically-ill in hospital alongside other support such as mechanical ventilation - is likely to be limited in settings with low healthcare capacity or where uncontrolled epidemics overwhelm hospitals; it may avert 22% of deaths in high-income countries and 8% in low-income countries (assuming R=1.35).

• Therapeutics for different patient populations (e.g. non-hospitalised) and types of benefit (reducing disease severity/infectiousness, preventing hospitalisation) may have greater benefits, particularly in resource-poor settings.

Back to menu Guidance and consensus statements

Publication Date

Title/URL Journal / Article type

18.06.2021 SCWG: What are the appropriate mitigations to deploy in care homes in the context of the post vaccination risk landscape?, 26 May 2021

Gov.uk (non-peer reviewed) / Research and analysis

23.06.2021 Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis

Intensive Care Med / Expert panel

Back to menu Overviews, comments and editorials

Publication Date

Title/URL Journal / Article type

17.06.2021 Detection of SARS-CoV-2 variants requires urgent global coordination Int J Infect Dis / Perspectives

23.06.2021 SARS-CoV-2 Variants and Vaccines N Engl J Med / Special Report

18.06.2021 Covid-19 vaccine outreach: "local knowledge, contacts, and credibility really, really matter"

BMJ / Feature

22.06.2021 Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom

Clin Trials / Article

23.06.2021 COVID-19 and the multisystem inflammatory syndrome in children: how vulnerable are the kidneys?

Kidney Int / Commentary

25.06.2021 Test and trace in England – progress update National Audit Office / Report

17.06.2021 Imatinib in COVID-19: hope and caution Lancet Respir Med / Comment

21.06.2021 Has SARS-CoV-2 reached peak fitness? Nat Med / Correspondence

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Produced by the PHE COVID-19 Literature Digest Team

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