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1.
Immunology ; 166(1): 68-77, 2022 05.
Article in English | MEDLINE | ID: covidwho-1685320

ABSTRACT

SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T-cell immunity. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS-CoV-2 wave and analysed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T-cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6·7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T-cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T-cell responses following both first and second dose vaccination. Trial registration: NCT04318314 and ISRCTN15677965.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/genetics , COVID-19 Vaccines , HLA-DRB1 Chains/genetics , Histocompatibility Antigens Class I/genetics , Humans , SARS-CoV-2
2.
Sci Transl Med ; 13(609): eabj0847, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1406600

ABSTRACT

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein­specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibody Formation , COVID-19 Vaccines , Humans
3.
Alcohol Alcohol ; 57(2): 203-210, 2022 Mar 12.
Article in English | MEDLINE | ID: covidwho-1369061

ABSTRACT

AIM: To assess the impact of Covid-19 on alcohol use disorders (AUD) and the role of universal alcohol screening (UAS) in an inpatient setting. METHODS: Retrospective cohorts were defined as pre-pandemic and pandemic admitted to Nottingham University Hospitals (April to October; 2019 and 2020) and had alcohol assessment by AUDIT-C. AUDIT-C score was assessed against age, sex, ethnicity, admission type, speciality and primary diagnosis of mental disorders. Subgroup analysis for Covid-19 positive patients was performed. RESULTS: A total of 63,927 admissions (47,954 patients) were included. The pandemic period compared to pre-pandemic had fewer overall admissions (27,349 vs 36,578, P < 0.001), fewer with AUD (17.6% vs 18.4%, P = 0.008) but a higher proportion of alcohol dependents (3.7% vs 3.0%, P < 0.0001). In the pandemic those with AUD were more likely to be male (P = 0.003), white (P < 0.001), in relationship (P < 0.001), of higher socioeconomic background (P < 0.001), have alcohol-related mental disorders (P = 0.002), emergency admission (P < 0.001), medical speciality admission (P < 0.001) and shorter length of stay (P < 0.033) compared to pre-pandemic AUD. Covid-19 positive patients with concomitant AUD died at younger age (P < 0.05) than Covid-19 positive patients at low risk for AUD. CONCLUSIONS: The pandemic changed the characteristics of inpatients with AUD. There was a higher proportion of alcohol-dependent admissions with evidence that a younger, less deprived group have been significantly impacted. UAS provides a useful tool to screen for AUD and to identify the change when facing sudden health crises.


Subject(s)
Alcoholism , COVID-19 , Alcohol Drinking , Alcoholism/diagnosis , Alcoholism/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Inpatients , Male , Retrospective Studies
4.
Sci Transl Med ; 13(609): eabj0847, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1352520

ABSTRACT

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein­specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibody Formation , COVID-19 Vaccines , Humans
5.
Endocrinol Diabetes Metab ; 4(2): e00215, 2021 04.
Article in English | MEDLINE | ID: covidwho-1086347

ABSTRACT

Background: COVID-19 has a broad clinical spectrum. We investigated the role of serum markers measured on admission on severity as assessed at discharge and investigated those which relate to the effect of BMI on severity. Methods: Clinical and laboratory data from 610 COVID-19 cases hospitalized in the province of Zheijang, China were investigated as risk factors for severe COVID-19 (assessed by respiratory distress) compared to mild or common forms using logistic regression methods. Biochemical markers were correlated with severity using spearman correlations, and a ROC analysis was used to determine the individual contribution of each of the biochemical markers on severity. We carried out formal mediation analyses to investigate the extent of the effect of body mass index (BMI) on COVID-19 severity mediated by hypertension, glycemia, Lactose Dehydrogenase (LDH) at the time of hospitalization and C-Reactive Protein levels (CRP), in units of standard deviations. Results: The individual markers measured on admission contributing most strongly to prediction of COVID-19 severity as assessed at discharge were LDH, CRP and glucose. The proportion of the effect of BMI on severity of COVID-19 mediated by CRP, glycemia or hypertension, we find that glucose mediated 79% (p < .0001), LDH mediated 78% (p < .0001), hypertension mediated 66% (p < .0001); however, only 44% (p < .005) was mediated by systemic inflammation (CRP). Conclusion: Our data indicate that a larger proportion of the effect of BMI on severity of COVID-19 is mediated by glycemia and LDH levels whereas less than half of it is mediated by systemic inflammation.


Subject(s)
Blood Glucose/metabolism , COVID-19/blood , COVID-19/pathology , Hypertension/complications , L-Lactate Dehydrogenase/blood , Adult , Biomarkers/blood , Body Mass Index , C-Reactive Protein/metabolism , COVID-19/complications , COVID-19/physiopathology , China , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index
6.
Front Med (Lausanne) ; 7: 607786, 2020.
Article in English | MEDLINE | ID: covidwho-1069727

ABSTRACT

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

7.
Clin Pharmacol Ther ; 108(6): 1185-1194, 2020 12.
Article in English | MEDLINE | ID: covidwho-754870

ABSTRACT

This study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of coronavirus disease 2019 (COVID-19) in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zhejiang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zhejiang, China, we tested the role of usage of cardiovascular, antidiabetic, and other medications on risk and severity of COVID-19. Analyses were adjusted for age, sex, and body mass index and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk (odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.2-2.3) of manifesting symptoms of COVID-19, whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR = 0.22, 95% CI 0.15-0.30 and OR = 0.30, 95% CI 0.19-0.58, respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR = 6.02, 95% CI 2.3-15.5) and insulin (OR = 2.71, 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR = 0.11, 95% CI 0.1-0.3) among with patients with COVID-19. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity.


Subject(s)
Antihypertensive Agents/therapeutic use , COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Hypertension/drug therapy , Hypoglycemic Agents/therapeutic use , Adult , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use , Cardiovascular Agents/therapeutic use , Case-Control Studies , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypertension/epidemiology , Insulin/therapeutic use , Middle Aged , Risk Factors , SARS-CoV-2 , Severity of Illness Index
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