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1.
Immunology ; 165(2): 250-259, 2022 02.
Article in English | MEDLINE | ID: covidwho-1511322

ABSTRACT

Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH 1-type cytokines. Highly significant differential IFN-γ+ /IL-2+ SARS-CoV-2-specific T-cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison with unknown / naïve individuals (p < 0·0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T-cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients (p < 0·0001). A second dose was sufficient to boost T-cell responses in the majority (90·6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (p = 0·034). Three-month post-vaccination T-cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardizable test ensures accurate and comparable assessments of SARS-CoV-2-specific T-cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Carrier State/immunology , Immunity, Cellular , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Th1 Cells/immunology , Vaccination , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , Female , Humans , Interferon-gamma/immunology , Male , Middle Aged
2.
Ann Clin Biochem ; 58(2): 123-131, 2021 03.
Article in English | MEDLINE | ID: covidwho-1067019

ABSTRACT

BACKGROUND: Serological assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried blood spot (DBS) testing offers significant advantages as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory. METHODS: A pathway utilizing a newborn screening laboratory infrastructure was developed using an enzyme-linked immunosorbent assay to detect IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein in DBS specimens. Paired plasma and DBS specimens from SARS-CoV-2 antibody-positive and -negative subjects and polymerase chain reaction positive subjects were tested. DBS specimen stability, effect of blood volume and punch location were also evaluated. RESULTS: DBS specimens from antibody-negative (n = 85) and -positive (n = 35) subjects and polymerase chain reaction positive subjects (n = 11) had a mean (SD; range) optical density (OD) of 0.14 (0.046; 0.03-0.27), 0.98 (0.41; 0.31-1.64) and 1.12 (0.37; 0.49-1.54), respectively. An action value OD >0.28 correctly assigned all cases. The weighted Deming regression for comparison of the DBS and the plasma assay yielded: y = 0.004041 + 1.005x, r = 0.991, Sy/x 0.171, n = 82. Extraction efficiency of antibodies from DBS specimens was >99%. DBS specimens were stable for at least 28 days at ambient room temperature and humidity. CONCLUSIONS: SARS-CoV-2 IgG receptor-binding domain antibodies can be reliably detected in DBS specimens. DBS serological testing offers lower costs than either point of care or serum/plasma assays that require patient travel, phlebotomy and hospital/clinic resources; the development of a DBS assay may be particularly important for resource poor settings.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing , COVID-19/immunology , Dried Blood Spot Testing , Immunoglobulin G/immunology , SARS-CoV-2/immunology , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Spike Glycoprotein, Coronavirus/immunology
3.
PLoS One ; 16(1): e0245382, 2021.
Article in English | MEDLINE | ID: covidwho-1048816

ABSTRACT

Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of SARS-CoV-2 seroconversion and the time frame for the development of antibodies with protective potential may help to explain the different clinical presentations of COVID-19. Furthermore, accurate descriptions of seroconversion are needed to inform the best use of serological assays for diagnostic testing and serosurveillance studies. Here, we describe the humoral responses in a cohort of hospitalised COVID-19 patients (n = 19) shortly following the onset of symptoms. Commercial and 'in-house' serological assays were used to measure IgG antibodies against different SARS-CoV-2 structural antigens-Spike (S) S1 sub-unit and Nucleocapsid protein (NP)-and to assess the potential for virus neutralisation mediated specifically by inhibition of binding between the viral attachment protein (S protein) and cognate receptor (ACE-2). Antibody response kinetics varied amongst the cohort, with patients seroconverting within 1 week, between 1-2 weeks, or after 2 weeks, following symptom onset. Anti-NP IgG responses were generally detected earlier, but reached maximum levels slower, than anti-S1 IgG responses. The earliest IgG antibodies produced by all patients included those that recognised the S protein receptor-binding domain (RBD) and were capable of inhibiting binding to ACE-2. These data revealed events and patterns of SARS-CoV-2 seroconversion that may be important predictors of the outcome of infection and guide the delivery of clinical services in the COVID-19 response.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , Aged , Aged, 80 and over , Antibodies, Viral/immunology , Cohort Studies , Coronavirus Nucleocapsid Proteins/chemistry , Female , Hospitalization , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Phosphoproteins/chemistry , SARS-CoV-2/chemistry , Seroconversion , Spike Glycoprotein, Coronavirus/chemistry , Wales
4.
Nat Commun ; 11(1): 6385, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-977267

ABSTRACT

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Immunity, Humoral/drug effects , SARS-CoV-2/drug effects , Adenosine Monophosphate/therapeutic use , Adult , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/virology , Fever/prevention & control , Humans , Immunity, Humoral/immunology , Lymphocyte Count , Male , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Treatment Outcome
6.
Br J Psychol ; 111(4): 603-629, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-657306

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has caused the coronavirus disease 2019 (COVID-19) pandemic represents the greatest international biopsychosocial emergency the world has faced for a century, and psychological science has an integral role to offer in helping societies recover. The aim of this paper is to set out the shorter- and longer-term priorities for research in psychological science that will (a) frame the breadth and scope of potential contributions from across the discipline; (b) enable researchers to focus their resources on gaps in knowledge; and (c) help funders and policymakers make informed decisions about future research priorities in order to best meet the needs of societies as they emerge from the acute phase of the pandemic. The research priorities were informed by an expert panel convened by the British Psychological Society that reflects the breadth of the discipline; a wider advisory panel with international input; and a survey of 539 psychological scientists conducted early in May 2020. The most pressing need is to research the negative biopsychosocial impacts of the COVID-19 pandemic to facilitate immediate and longer-term recovery, not only in relation to mental health, but also in relation to behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness. We call on psychological scientists to work collaboratively with other scientists and stakeholders, establish consortia, and develop innovative research methods while maintaining high-quality, open, and rigorous research standards.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Psychology/trends , Adult , COVID-19 , Female , Humans , Male , Middle Aged , Pandemics , Research Design
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