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  1. Article ; Online: Under-representation of the WHO African region in clinical trials of interventions against hepatitis B virus infection.

    Delphin, Marion / Mohammed, Khadija Said / Downs, Louise O / Lumley, Sheila F / Waddilove, Elizabeth / Okanda, Dorcas / Aliyan, Nadia / Van Schalkwyk, Marije / Anderson, Motswedi / Ocama, Ponsiano / Maponga, Tongai / Torimiro, Judith / Iwuji, Collins / Ndung'u, Thumbi / Matthews, Philippa C / Taljaard, Jantjie

    The lancet. Gastroenterology & hepatology

    2024  Volume 9, Issue 4, Page(s) 383–392

    Abstract: The WHO African region bears a disproportionate burden of morbidity and mortality related to chronic hepatitis B virus (HBV) infection and accounts for an estimated 70% of new HBV infections worldwide. We investigated the extent to which HBV clinical ... ...

    Abstract The WHO African region bears a disproportionate burden of morbidity and mortality related to chronic hepatitis B virus (HBV) infection and accounts for an estimated 70% of new HBV infections worldwide. We investigated the extent to which HBV clinical trials represented populations in this region by searching the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for interventional clinical trials published in English between database inception and May 29, 2023, using the search term "Hepatitis B". We identified 1804 unique clinical trials, of which 18 (1·0%) recorded involvement of the WHO African region. There is no evidence that the number of HBV clinical trials in this region has improved over time. The diversity of new interventions and industry sponsorship in the WHO African region were low, with trials of HBV comparing poorly with those of other endemic infectious diseases (eg, malaria, HIV, and SARS-CoV-2). HBV research and clinical trial investigations have neglected the WHO African region, leading to profound health inequities. HBV clinical trials are urgently needed to evaluate the efficacy of newly discovered therapeutics and to ensure that interventions can be equitably distributed and deployed as they become available.
    MeSH term(s) Humans ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy ; Hepatitis B, Chronic/epidemiology ; Hepatitis B/drug therapy ; Hepatitis B/epidemiology ; Hepatitis B/prevention & control ; World Health Organization
    Language English
    Publishing date 2024-02-15
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 2468-1253
    ISSN (online) 2468-1253
    DOI 10.1016/S2468-1253(23)00315-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Estimating hepatitis B virus cccDNA persistence in chronic infection.

    Lythgoe, Katrina A / Lumley, Sheila F / Pellis, Lorenzo / McKeating, Jane A / Matthews, Philippa C

    Virus evolution

    2020  Volume 7, Issue 1, Page(s) veaa063

    Abstract: Hepatitis B virus (HBV) infection is a major global health problem with over 240 million infected individuals at risk of developing progressive liver disease and hepatocellular carcinoma. HBV is an enveloped DNA virus that establishes its genome as an ... ...

    Abstract Hepatitis B virus (HBV) infection is a major global health problem with over 240 million infected individuals at risk of developing progressive liver disease and hepatocellular carcinoma. HBV is an enveloped DNA virus that establishes its genome as an episomal, covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Currently, available standard-of-care treatments for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) that suppress HBV replication but do not target the cccDNA and hence rarely cure infection. There is considerable interest in determining the lifespan of cccDNA molecules to design and evaluate new curative treatments. We took a novel approach to this problem by developing a new mathematical framework to model changes in evolutionary rates during infection which, combined with previously determined within-host evolutionary rates of HBV, we used to determine the lifespan of cccDNA. We estimate that during HBe-antigen positive (HBeAg
    Language English
    Publishing date 2020-08-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veaa063
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Multiplex PCR reveals high prevalence of enterovirus and HHV6 in acellular paediatric cerebrospinal fluid samples.

    Lumley, Sheila F / Pritchard, Dave / Dutta, Atanu / Matthews, Philippa C / Cann, Kathy

    The Journal of infection

    2018  Volume 77, Issue 3, Page(s) 249–257

    MeSH term(s) Child ; Enterovirus ; Enterovirus Infections ; Herpesvirus 6, Human ; Humans ; Multiplex Polymerase Chain Reaction ; Prevalence ; Tuberculosis, Meningeal
    Language English
    Publishing date 2018-05-29
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2018.05.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Are the Patterns of Cytomegalovirus Viral Load Seen After Solid Organ Transplantation Affected by Circadian Rhythm?

    Rafferty, Hannah / Murray, Matthew J / Tam, Jerry C H / Macfarlane, Alastair / Smith, Colette / Lumley, Sheila F / Atabani, Sowsan / McKeating, Jane A / Sharma, Dinesh / Reeves, Matthew / Whitmore, David / Griffiths, Paul

    The Journal of infectious diseases

    2022  Volume 226, Issue 2, Page(s) 357–365

    Abstract: Background: Cytomegalovirus (CMV) is an important opportunistic pathogen after transplantation. Some virological variation in transplant recipients is explained by donor and recipient CMV serostatus, but not all. Circadian variability of herpesviruses ... ...

    Abstract Background: Cytomegalovirus (CMV) is an important opportunistic pathogen after transplantation. Some virological variation in transplant recipients is explained by donor and recipient CMV serostatus, but not all. Circadian variability of herpesviruses has been described, so we investigated the effect of time of day of transplantation on posttransplant CMV viremia.
    Methods: We performed a retrospective analysis of 1517 patients receiving liver or kidney allografts at a single center from 2002 to 2018. All patients were given preemptive therapy with CMV viremia monitoring after transplantation. Circulatory arrest and reperfusion time of donor organ were categorized into 4 periods. Patients were divided into serostatus groups based on previous CMV infection in donor and recipient. CMV viremia parameters were compared between time categories for each group. Factor analysis of mixed data was used to interrogate this complex data set.
    Results: Live-donor transplant recipients were less likely to develop viremia than recipients of deceased-donor organs (48% vs 61%; P < .001). After controlling for this, there was no evidence of time of day of transplantation affecting CMV parameters in any serostatus group, by logistic regression or factor analysis of mixed data.
    Discussion: We found no evidence for a circadian effect of transplantation on CMV viremia, but these novel results warrant confirmation by other centers.
    MeSH term(s) Antiviral Agents/therapeutic use ; Circadian Rhythm ; Cytomegalovirus ; Cytomegalovirus Infections ; Humans ; Organ Transplantation/adverse effects ; Retrospective Studies ; Viral Load ; Viremia/etiology
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2022-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Hepatitis B Virus Adaptation to the CD8+ T Cell Response: Consequences for Host and Pathogen.

    Lumley, Sheila F / McNaughton, Anna L / Klenerman, Paul / Lythgoe, Katrina A / Matthews, Philippa C

    Frontiers in immunology

    2018  Volume 9, Page(s) 1561

    Abstract: Chronic viral hepatitis infections are a major public health concern, with an estimated 290 million individuals infected with hepatitis B virus (HBV) globally. This virus has been a passenger in human populations for >30,000 years, and remains highly ... ...

    Abstract Chronic viral hepatitis infections are a major public health concern, with an estimated 290 million individuals infected with hepatitis B virus (HBV) globally. This virus has been a passenger in human populations for >30,000 years, and remains highly prevalent in some settings. In order for this endemic pathogen to persist, viral adaptation to host immune responses is pre-requisite. Here, we focus on the interplay between HBV infection and the CD8+ T cell response. We present the evidence that CD8+ T cells play an important role in control of chronic HBV infection and that the selective pressure imposed on HBV through evasion of these immune responses can potentially influence viral diversity, chronicity, and the outcome of infection, and highlight where there are gaps in current knowledge. Understanding the nature and mechanisms of HBV evolution and persistence could shed light on differential disease outcomes, including cirrhosis and hepatocellular carcinoma, and help reach the goal of global HBV elimination by guiding the design of new strategies, including vaccines and therapeutics.
    Language English
    Publishing date 2018-07-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.01561
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Time of Day of Vaccination Affects SARS-CoV-2 Antibody Responses in an Observational Study of Health Care Workers.

    Wang, Wei / Balfe, Peter / Eyre, David W / Lumley, Sheila F / O'Donnell, Denise / Warren, Fiona / Crook, Derrick W / Jeffery, Katie / Matthews, Philippa C / Klerman, Elizabeth B / McKeating, Jane A

    Journal of biological rhythms

    2021  Volume 37, Issue 1, Page(s) 124–129

    Abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced ... ...

    Abstract The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time of day of vaccination has been reported to influence host immune responses to multiple pathogens, we quantified the influence of SARS-CoV-2 vaccination time, vaccine type, participant age, sex, and days post-vaccination on anti-Spike antibody responses in health care workers. The magnitude of the anti-Spike antibody response is associated with the time of day of vaccination, vaccine type, participant age, sex, and days post-vaccination. These results may be relevant for optimising SARS-CoV-2 vaccine efficacy.
    MeSH term(s) Antibody Formation ; COVID-19 ; COVID-19 Vaccines ; Circadian Rhythm ; Health Personnel ; Humans ; Pandemics ; SARS-CoV-2 ; Vaccination
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2021-12-04
    Publishing country United States
    Document type Letter ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 896387-3
    ISSN 1552-4531 ; 0748-7304
    ISSN (online) 1552-4531
    ISSN 0748-7304
    DOI 10.1177/07487304211059315
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Transmission of community- and hospital-acquired SARS-CoV-2 in hospital settings in the UK: A cohort study.

    Mo, Yin / Eyre, David W / Lumley, Sheila F / Walker, Timothy M / Shaw, Robert H / O'Donnell, Denise / Butcher, Lisa / Jeffery, Katie / Donnelly, Christl A / Cooper, Ben S

    PLoS medicine

    2021  Volume 18, Issue 10, Page(s) e1003816

    Abstract: Background: Nosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. Identifying the risk factors and drivers for ... ...

    Abstract Background: Nosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. Identifying the risk factors and drivers for these nosocomial transmissions is critical for infection prevention and control interventions. The main aim of our study was to quantify the relative importance of different transmission pathways of SARS-CoV-2 in the hospital setting.
    Methods and findings: This is an observational cohort study using data from 4 teaching hospitals in Oxfordshire, United Kingdom, from January to October 2020. Associations between infectious SARS-CoV-2 individuals and infection risk were quantified using logistic, generalised additive and linear mixed models. Cases were classified as community- or hospital-acquired using likely incubation periods of 3 to 7 days. Of 66,184 patients who were hospitalised during the study period, 920 had a positive SARS-CoV-2 PCR test within the same period (1.4%). The mean age was 67.9 (±20.7) years, 49.2% were females, and 68.5% were from the white ethnic group. Out of these, 571 patients had their first positive PCR tests while hospitalised (62.1%), and 97 of these occurred at least 7 days after admission (10.5%). Among the 5,596 HCWs, 615 (11.0%) tested positive during the study period using PCR or serological tests. The mean age was 39.5 (±11.1) years, 78.9% were females, and 49.8% were nurses. For susceptible patients, 1 day in the same ward with another patient with hospital-acquired SARS-CoV-2 was associated with an additional 7.5 infections per 1,000 susceptible patients (95% credible interval (CrI) 5.5 to 9.5/1,000 susceptible patients/day) per day. Exposure to an infectious patient with community-acquired Coronavirus Disease 2019 (COVID-19) or to an infectious HCW was associated with substantially lower infection risks (2.0/1,000 susceptible patients/day, 95% CrI 1.6 to 2.2). As for HCW infections, exposure to an infectious patient with hospital-acquired SARS-CoV-2 or to an infectious HCW were both associated with an additional 0.8 infection per 1,000 susceptible HCWs per day (95% CrI 0.3 to 1.6 and 0.6 to 1.0, respectively). Exposure to an infectious patient with community-acquired SARS-CoV-2 was associated with less than half this risk (0.2/1,000 susceptible HCWs/day, 95% CrI 0.2 to 0.2). These assumptions were tested in sensitivity analysis, which showed broadly similar results. The main limitations were that the symptom onset dates and HCW absence days were not available.
    Conclusions: In this study, we observed that exposure to patients with hospital-acquired SARS-CoV-2 is associated with a substantial infection risk to both HCWs and other hospitalised patients. Infection control measures to limit nosocomial transmission must be optimised to protect both staff and patients from SARS-CoV-2 infection.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; COVID-19/transmission ; Cohort Studies ; Community-Acquired Infections ; Cross Infection/epidemiology ; Female ; Health Personnel ; Hospitalization ; Hospitals/statistics & numerical data ; Humans ; Infection Control ; Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data ; Infectious Disease Transmission, Professional-to-Patient/statistics & numerical data ; Male ; Middle Aged ; Nurses ; Risk Factors ; SARS-CoV-2 ; United Kingdom/epidemiology
    Language English
    Publishing date 2021-10-12
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2185925-5
    ISSN 1549-1676 ; 1549-1277
    ISSN (online) 1549-1676
    ISSN 1549-1277
    DOI 10.1371/journal.pmed.1003816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Changes in paediatric respiratory infections at a UK teaching hospital 2016-2021; impact of the SARS-CoV-2 pandemic.

    Lumley, Sheila F / Richens, Nicholas / Lees, Emily / Cregan, Jack / Kalimeris, Elizabeth / Oakley, Sarah / Morgan, Marcus / Segal, Shelley / Dawson, Moya / Walker, A Sarah / Eyre, David W / Crook, Derrick W / Beer, Sally / Novak, Alex / Stoesser, Nicole E / Matthews, Philippa C

    The Journal of infection

    2021  Volume 84, Issue 1, Page(s) 40–47

    Abstract: Objective To describe the impact of the SARS-CoV-2 pandemic on the incidence of paediatric viral respiratory tract infection in Oxfordshire, UK. Methods Data on paediatric Emergency Department (ED) attendances (0-15 years inclusive), respiratory virus ... ...

    Abstract Objective To describe the impact of the SARS-CoV-2 pandemic on the incidence of paediatric viral respiratory tract infection in Oxfordshire, UK. Methods Data on paediatric Emergency Department (ED) attendances (0-15 years inclusive), respiratory virus testing, vital signs and mortality at Oxford University Hospitals were summarised using descriptive statistics. Results Between 1-March-2016 and 30-July-2021, 155,056 ED attendances occurred and 7,195 respiratory virus PCRs were performed. Detection of all pathogens was suppressed during the first national lockdown. Rhinovirus and adenovirus rates increased when schools reopened September-December 2020, then fell, before rising in March-May 2021. The usual winter RSV peak did not occur in 2020/21, with an inter-seasonal rise (32/1,000 attendances in 0-3 yr olds) in July 2021. Influenza remained suppressed throughout. A higher paediatric early warning score (PEWS) was seen for attendees with adenovirus during the pandemic compared to pre-pandemic (p = 0.04, Mann-Witney U test), no other differences in PEWS were seen. Conclusions SARS-CoV-2 caused major changes in the incidence of paediatric respiratory viral infection in Oxfordshire, with implications for clinical service demand, testing strategies, timing of palivizumab RSV prophylaxis, and highlighting the need to understand which public health interventions are most effective for preventing respiratory virus infections.
    MeSH term(s) COVID-19 ; Child ; Communicable Disease Control ; Hospitals, Teaching ; Humans ; Pandemics ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Tract Infections/epidemiology ; SARS-CoV-2 ; United Kingdom
    Language English
    Publishing date 2021-10-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2021.10.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Transmission of community- and hospital-acquired SARS-CoV-2 in hospital settings in the UK

    Yin Mo / David W Eyre / Sheila F Lumley / Timothy M Walker / Robert H Shaw / Denise O'Donnell / Lisa Butcher / Katie Jeffery / Christl A Donnelly / Oxford COVID infection review team / Ben S Cooper

    PLoS Medicine, Vol 18, Iss 10, p e

    A cohort study.

    2021  Volume 1003816

    Abstract: Background Nosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. Identifying the risk factors and drivers for ... ...

    Abstract Background Nosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. Identifying the risk factors and drivers for these nosocomial transmissions is critical for infection prevention and control interventions. The main aim of our study was to quantify the relative importance of different transmission pathways of SARS-CoV-2 in the hospital setting. Methods and findings This is an observational cohort study using data from 4 teaching hospitals in Oxfordshire, United Kingdom, from January to October 2020. Associations between infectious SARS-CoV-2 individuals and infection risk were quantified using logistic, generalised additive and linear mixed models. Cases were classified as community- or hospital-acquired using likely incubation periods of 3 to 7 days. Of 66,184 patients who were hospitalised during the study period, 920 had a positive SARS-CoV-2 PCR test within the same period (1.4%). The mean age was 67.9 (±20.7) years, 49.2% were females, and 68.5% were from the white ethnic group. Out of these, 571 patients had their first positive PCR tests while hospitalised (62.1%), and 97 of these occurred at least 7 days after admission (10.5%). Among the 5,596 HCWs, 615 (11.0%) tested positive during the study period using PCR or serological tests. The mean age was 39.5 (±11.1) years, 78.9% were females, and 49.8% were nurses. For susceptible patients, 1 day in the same ward with another patient with hospital-acquired SARS-CoV-2 was associated with an additional 7.5 infections per 1,000 susceptible patients (95% credible interval (CrI) 5.5 to 9.5/1,000 susceptible patients/day) per day. Exposure to an infectious patient with community-acquired Coronavirus Disease 2019 (COVID-19) or to an infectious HCW was associated with substantially lower infection risks (2.0/1,000 susceptible patients/day, 95% CrI 1.6 to 2.2). As for HCW infections, exposure to an infectious patient with hospital-acquired SARS-CoV-2 or to an infectious HCW were both associated with an additional 0.8 infection per 1,000 susceptible HCWs per day (95% CrI 0.3 to 1.6 and 0.6 to 1.0, respectively). Exposure to an infectious patient with community-acquired SARS-CoV-2 was associated with less than half this risk (0.2/1,000 susceptible HCWs/day, 95% CrI 0.2 to 0.2). These assumptions were tested in sensitivity analysis, which showed broadly similar results. The main limitations were that the symptom onset dates and HCW absence days were not available. Conclusions In this study, we observed that exposure to patients with hospital-acquired SARS-CoV-2 is associated with a substantial infection risk to both HCWs and other hospitalised patients. Infection control measures to limit nosocomial transmission must be optimised to protect both staff and patients from SARS-CoV-2 infection.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Time of day of vaccination affects SARS-CoV-2 antibody responses in an observational study of healthcare workers

    Wang, Wei / Balfe, Peter / Eyre, David W / Lumley, Sheila F / O'Donnell, Denise / Warren, Fiona / Crook, Derrick W / Jeffery, Katie / Matthews, Philippa C / Klerman, Elizabeth B / McKeating, Jane

    medRxiv

    Abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced ... ...

    Abstract The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time-of-day of vaccination has been reported to influence host immune responses to multiple pathogens, we quantified the influence of SARS-CoV-2 vaccination time, vaccine type, age, sex, and days post-vaccination on anti-Spike antibody responses in healthcare workers. The magnitude of the anti-Spike antibody response associated with the time-of-day of vaccination, vaccine type, participant age, sex, and days post vaccination. These results may be relevant for optimizing SARS-CoV-2 vaccine efficacy.
    Keywords covid19
    Language English
    Publishing date 2021-10-29
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.10.28.21265499
    Database COVID19

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