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1.
Lancet Microbe ; 2021 Nov 09.
Article in English | MEDLINE | ID: covidwho-1510521

ABSTRACT

Background: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer-BioNTech) mRNA vaccine. Methods: We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3-4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. Findings: Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232-285). At 28 days (IQR 27-33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150-461] vs 55 [IQR 24-132] spot-forming units [SFUs] per 106 PBMCs; p<0·0001). With cryopreserved PBMCs, the T-cell response in previously infected individuals (n=52) after one vaccine dose was equivalent to that of infection-naive individuals (n=19) after receiving two vaccine doses (median 152 [IQR 119-275] vs 162 [104-258] SFUs/106 PBMCs; p=1·00). Anti-spike IgG antibody responses following a single dose in 142 previously infected health-care workers (median 270 373 [IQR 203 461-535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099-55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221-242 467] AU/mL; p<0·0001). Interpretation: A single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern. Future studies should determine the additional benefit of a second dose on the magnitude and durability of immune responses in individuals vaccinated following infection, alongside evaluation of the impact of extending the interval between vaccine doses. Funding: UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium.

2.
Cell ; 184(23): 5699-5714.e11, 2021 11 11.
Article in English | MEDLINE | ID: covidwho-1466093

ABSTRACT

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.


Subject(s)
COVID-19 Vaccines/immunology , Vaccines, Synthetic/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Cross-Priming/immunology , Dose-Response Relationship, Immunologic , Female , Humans , Immunity , Immunoglobulin G/immunology , Linear Models , Male , Middle Aged , Reference Standards , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Treatment Outcome , Young Adult
3.
Nat Commun ; 12(1): 5061, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361634

ABSTRACT

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Monoclonal/blood , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Antibodies, Neutralizing/metabolism , Antibodies, Viral/blood , Antibodies, Viral/immunology , Carrier Proteins , Epitopes , Humans , Immunity , SARS-CoV-2/drug effects , T-Lymphocytes/immunology
4.
Lancet HIV ; 8(8): e474-e485, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275800

ABSTRACT

BACKGROUND: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. METHODS: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18-55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per µL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4-6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing. FINDINGS: Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2-49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per µL (IQR 573·5-859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704-2728]; n=50) and were sustained until day 56 (median 941 EUs [531-1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (p>0·05 for all analyses). INTERPRETATION: In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , HIV Infections/immunology , SARS-CoV-2/immunology , Adult , CD4 Lymphocyte Count , COVID-19 Vaccines/adverse effects , HIV Infections/drug therapy , Humans , Male , Middle Aged , Vaccination
6.
Nat Commun ; 12(1): 1951, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1157905

ABSTRACT

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests do not require special equipment, are read by eye, have short development times, low cost and can be applied at the Point of Care. Here we describe a quantitative Haemagglutination test (HAT) for the detection of antibodies to the receptor binding domain of the SARS-CoV-2 spike protein. The HAT has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. We will supply aliquots of the test reagent sufficient for ten thousand test wells free of charge to qualified research groups anywhere in the world.


Subject(s)
Antibodies, Viral/analysis , COVID-19 Testing/methods , COVID-19/diagnosis , Hemagglutination Tests/methods , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology , Agglutination Tests/methods , Antibodies, Monoclonal/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Enzyme-Linked Immunosorbent Assay/methods , Humans , Point-of-Care Systems , Polymerase Chain Reaction , SARS-CoV-2/immunology , Sensitivity and Specificity , Seroconversion
7.
Clin Chim Acta ; 512: 58-62, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-956958

ABSTRACT

OBJECTIVE: It is unclear if implementation of biosafety action plans in response to the COVID-19 pandemic has affected laboratory quality metrics. METHODS: This retrospective study used quality data, including turnaround time (TAT) and number/type of unacceptable specimens from a stat laboratory supporting an outpatient medical clinic serving predominantly elderly cancer patients. Four months of data from the height of the COVID-19 pandemic (March-June 2020) were compared to the same months in 2019. RESULTS: March-May 2020 test volumes were decreased compared to 2019. June 2020 test volume was slightly increased compared to 2019. TATs in 2020 were similar/ slightly improved compared to the same months in 2019, due to shortened collect to receive and receive to verify TATs. The number and types of unacceptable specimens were similar in 2020 and 2019. CONCLUSIONS: Despite the challenges to the system caused by the pandemic, laboratory quality metrics were maintained.


Subject(s)
COVID-19 , Laboratories/statistics & numerical data , Aged , COVID-19/epidemiology , Containment of Biohazards/standards , Humans , Laboratories/standards , Neoplasms , Pandemics , Retrospective Studies , Specimen Handling/standards , Specimen Handling/statistics & numerical data , Time Factors
8.
BMJ Glob Health ; 5(11)2020 Nov.
Article in English | MEDLINE | ID: covidwho-926463

ABSTRACT

BACKGROUND: There are reports of outbreaks of COVID-19 in prisons in many countries. Responses to date have been highly variable and it is not clear whether public health guidance has been informed by the best available evidence. We conducted a systematic review to synthesise the evidence on outbreaks of highly contagious diseases in prison. METHODS: We searched seven electronic databases for peer-reviewed articles and official reports published between 1 January 2000 and 28 July 2020. We included quantitative primary research that reported an outbreak of a given contagious disease in a correctional facility and examined the effects of interventions. We excluded studies that did not provide detail on interventions. We synthesised common themes using the Synthesis Without Meta-analysis (SWiM) guideline, identified gaps in the literature and critically appraised the effectiveness of various containment approaches. RESULTS: We identified 28 relevant studies. Investigations were all based in high-income countries and documented outbreaks of tuberculosis, influenza (types A and B), varicella, measles, mumps, adenovirus and COVID-19. Several themes were common to these reports, including the public health implications of infectious disease outbreaks in prison, and the role of interagency collaboration, health communication, screening for contagious diseases, restriction, isolation and quarantine, contact tracing, immunisation programmes, epidemiological surveillance and prison-specific guidelines in addressing any outbreaks. DISCUSSION: Prisons are high-risk settings for the transmission of contagious diseases and there are considerable challenges in managing outbreaks in them. A public health approach to managing COVID-19 in prisons is required. PROSPERO REGISTRATION NUMBER: CRD42020178827.


Subject(s)
COVID-19 , Communicable Disease Control , Communicable Diseases , Disease Outbreaks/prevention & control , Prisons , Adolescent , Adult , Aged , COVID-19/prevention & control , COVID-19/therapy , COVID-19/transmission , Communicable Diseases/therapy , Communicable Diseases/transmission , Contact Tracing , Female , Health Communication , Humans , Male , Mass Screening , Middle Aged , Public Health , SARS-CoV-2 , Young Adult
9.
Int J Lab Hematol ; 43(2): 148-159, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-919216

ABSTRACT

The ongoing COVID-19 pandemic has had a profound worldwide impact on the laboratory hematology community. Nevertheless, the pace of COVID-19 hematology-related research has continued to accelerate and has established the role of laboratory hematology data for many purposes including disease prognosis and outcome. The purpose of this scoping review was to assess the current state of COVID-19 laboratory hematology research. A comprehensive search of the literature published between December 1, 2019, and July 3, 2020, was performed, and we analyzed the sources, publication dates, study types, and topics of the retrieved studies. Overall, 402 studies were included in this scoping review. Approximately half of these studies (n = 202, 50.37%) originated in China. Retrospective cohort studies comprised the largest study type (n = 176, 43.89%). Prognosis/ risk factors, epidemiology, and coagulation were the most common topics. The number of studies published per day has increased through the end of May. The studies were heavily biased in favor of papers originating in China and on retrospective clinical studies with limited use of and reporting of laboratory data. Despite the major improvements in our understanding of the role of coagulation, automated hematology, and cell morphology in COVID-19, there are gaps in the literature, including biosafety and the laboratory role in screening and prevention of COVID-19. There is a gap in the publication of papers focused on guidelines for the laboratory. Our findings suggest that, despite the large number of publications related to laboratory data and their use in COVID-19 disease, many areas remain unexplored or under-reported.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Hematology/methods , Laboratories/organization & administration , Pandemics , Bibliometrics , Biomarkers/blood , Blood Cell Count , Blood Coagulation Factors/metabolism , Blood Coagulation Tests , COVID-19/blood , COVID-19/virology , China/epidemiology , Europe/epidemiology , Fibrin Fibrinogen Degradation Products/metabolism , Hematology/instrumentation , Humans , Prognosis , Retrospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index , United States/epidemiology
10.
Nat Immunol ; 21(11): 1336-1345, 2020 11.
Article in English | MEDLINE | ID: covidwho-889210

ABSTRACT

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.


Subject(s)
Antigens, Viral/immunology , Betacoronavirus/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Immunologic Memory/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/prevention & control , Epitopes, T-Lymphocyte/immunology , Humans , Immunodominant Epitopes/immunology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , United Kingdom , Viral Vaccines/immunology
11.
Preprint | SSRN | ID: ppcovidwho-1099

ABSTRACT

Background: There are reports of outbreaks of coronavirus disease 2019 (Covid-2019) in prisons in many countries. Responses to date have been highly variable an

12.
Int J Lab Hematol ; 42 Suppl 1: 11-18, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-602630

ABSTRACT

The ongoing COVID-19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID-19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID-19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID-19 infection, (c) summarize the current state of biomarker analysis in COVID-19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID-19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.


Subject(s)
Betacoronavirus/isolation & purification , Clinical Laboratory Services/organization & administration , Coronavirus Infections/epidemiology , Lymphopenia/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Thrombocytopenia/epidemiology , Antibodies, Viral/blood , Betacoronavirus/pathogenicity , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , COVID-19 Testing , China/epidemiology , Clinical Laboratory Techniques/methods , Communicable Disease Control , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Hematology/methods , Humans , Incidence , Italy/epidemiology , Laboratories/organization & administration , Lymphopenia/diagnosis , Lymphopenia/physiopathology , Personal Protective Equipment/supply & distribution , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , Procalcitonin/blood , SARS-CoV-2 , Thrombocytopenia/diagnosis , Thrombocytopenia/physiopathology , United States/epidemiology , Viral Proteins/blood
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