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1.
J Infect Dis ; 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1608338

ABSTRACT

BACKGROUND: Specialised pro-resolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in SARS-CoV-2 patients, and to identify potential relationships with innate responses and clinical outcome. METHODS: Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age and sex matched cohort collected prior to the pandemic (SARS-CoV-2 negative), were processed for quantification of bioactive lipids and anti-nucleocapsid and anti-spike quantitative binding assays. RESULTS: SARS-CoV-2 serum had significantly higher concentrations of omega-6 derived pro-inflammatory lipids and omega-6 and omega-3 derived SPMs, compared to age and sex matched SARS-CoV-2 negative group, which were not markedly altered by age or sex. There were significant positive correlations between SPMs, pro-inflammatory bioactive lipids and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid (LA) and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid (5,6-DHET) were significantly lower in SARS-COV-2 patients who died. DISCUSSION: SARS-COV-2 infection was associated with increased levels of specialised pro-resolution molecules and other pro- and anti-inflammatory bioactive lipids, supporting the future investigation of the underlying enzymatic pathways, which may inform the development of novel treatments.

2.
Nature ; 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1510600

ABSTRACT

Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1-3. We hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-24-11, would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T-cells, including those against the early transcribed replication transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCW) remaining repeatedly negative by PCR, antibody binding, and neutralisation (seronegative HCW, SN-HCW). SN-HCW had stronger, more multispecific memory T-cells than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). SN-HCW with the strongest RTC-specific T-cells had an increase in IFI27, a robust early innate signature of SARS-CoV-214, suggesting abortive infection. RNA-polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA-polymerase was preferentially targeted (amongst regions tested) by T-cells from pre-pandemic cohorts and SN-HCW. RTC epitope-specific T-cells cross-recognising HCoV variants were identified in SN-HCW. Enriched pre-existing RNA-polymerase-specific T-cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T-cells as targets for vaccines against endemic and emerging Coronaviridae.

3.
Lancet Infect Dis ; 21(7): 939-949, 2021 07.
Article in English | MEDLINE | ID: covidwho-1433943

ABSTRACT

BACKGROUND: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. METHODS: In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m2vs ≥30 kg/m2), and comorbidities (binary variable, with or without comorbidities). FINDINGS: Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49-68) for ChAdOx1 nCoV-19 and 69% (66-72) for BNT162b2 at 21-44 days and 72% (63-79) for BNT162b2 after 45-59 days. INTERPRETATION: Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. FUNDING: ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/immunology , Drug-Related Side Effects and Adverse Reactions/immunology , SARS-CoV-2/immunology , Vaccination/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Safety/statistics & numerical data , Self Report/statistics & numerical data , United Kingdom
6.
BMJ Nutr Prev Health ; 4(1): 149-157, 2021.
Article in English | MEDLINE | ID: covidwho-1325112

ABSTRACT

Objectives: Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection. Design: App-based community survey. Setting: 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373). Main exposure: Self-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020. Main outcome measures: SARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020. Results: In 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. Conclusion: In women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made.

7.
Science ; 2021 Apr 30.
Article in English | MEDLINE | ID: covidwho-1209815

ABSTRACT

SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.

8.
EClinicalMedicine ; 34: 100835, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1184950

ABSTRACT

Background: : Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population. We aimed to understand ethnic differences in SARS-CoV-2 seropositivity among hospital healthcare workers depending on their hospital role, socioeconomic status, Covid-19 symptoms and basic demographics. Methods: A prospective longitudinal observational cohort study. 1364 HCWs at five UK hospitals were studied with up to 16 weeks of symptom questionnaires and antibody testing (to both nucleocapsid and spike protein) during the first UK wave in five NHS hospitals between March 20 and July 10 2020. The main outcome measures were SARS-CoV-2 infection (seropositivity at any time-point) and symptoms. Registration number: NCT04318314. Findings: 272 of 1364 HCWs (mean age 40.7 years, 72% female, 74% White, ≥6 samples per participant) seroconverted, reporting predominantly mild or no symptoms. Seropositivity was lower in Intensive Therapy Unit (ITU) workers (OR=0.44 95%CI 0.24, 0.77; p=0.0035). Seropositivity was higher in Black (compared to White) participants, independent of age, sex, role and index of multiple deprivation (OR=2.61 95%CI 1.47-4.62 p=0.0009). No association was seen between White HCWs and other minority ethnic groups. Interpretation: In the UK first wave, Black ethnicity (but not other ethnicities) more than doubled HCWs likelihood of seropositivity, independent of age, sex, measured socio-economic factors and hospital role.

9.
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
10.
BMC Med ; 19(1): 37, 2021 02 11.
Article in English | MEDLINE | ID: covidwho-1079239

ABSTRACT

BACKGROUND: Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of COVID-19. METHODS: Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts. RESULTS: Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q < 0.1). No such association was seen with fruit intake. A mediation analysis found that 20.00% of the effect of vegetable intake on lymphocyte counts was mediated by one bacterial genus, Collinsella, known to increase with the intake of processed foods and previously associated with fatty liver disease. We further correlated white blood cells to other inflammatory markers including IL6 and GlycA, fasting and post-prandial glucose levels and found a significant relationship between inflammation and diet. CONCLUSION: A habitual diet high in vegetables, but not fruits, is linked to a lower inflammatory profile for white blood cells, and a fifth of the effect is mediated by the genus Collinsella. TRIAL REGISTRATION: The ClinicalTrials.gov registration identifier is NCT03479866 .


Subject(s)
Diet , Fruit , Gastrointestinal Microbiome/genetics , Leukocytes , Vegetables , Actinobacteria , Adult , Biomarkers/blood , COVID-19 , Clostridiales , Clostridium , Fasting , Female , Humans , Interleukin-6/blood , Leukocyte Count , Lymphocyte Count , Male , Mediation Analysis , Middle Aged , RNA, Ribosomal, 16S/genetics , Ruminococcus , SARS-CoV-2
11.
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.

12.
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
13.
Nat Med ; 26(7): 1037-1040, 2020 07.
Article in English | MEDLINE | ID: covidwho-232776

ABSTRACT

A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.


Subject(s)
Coronavirus Infections/diagnosis , Disease Notification/methods , Mobile Applications , Pneumonia, Viral/diagnosis , Prodromal Symptoms , Self Report , Smartphone , Adult , Aged , Betacoronavirus/physiology , COVID-19 , Computer Systems , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Cough/diagnosis , Cough/epidemiology , Disease Notification/standards , Dyspnea/diagnosis , Dyspnea/epidemiology , Fatigue/diagnosis , Fatigue/epidemiology , Female , Humans , Male , Middle Aged , Mobile Applications/standards , Models, Biological , Olfaction Disorders/diagnosis , Olfaction Disorders/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Prognosis , SARS-CoV-2 , Severity of Illness Index , Taste Disorders/diagnosis , Taste Disorders/epidemiology , United Kingdom/epidemiology , United States/epidemiology
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