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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336116

ABSTRACT

It is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged ≥16 years 35±8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.

2.
EBioMedicine ; 70: 103534, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1356204

ABSTRACT

Background In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria triggered the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a previous study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April, representing an exceptionally high level of local seropositivity in Europe. We performed a follow-up study in Ischgl, which is the first to show persistence of immunity and protection against SARS-CoV-2 and some of its variants at a community level. Methods Of the 1259 adults that participated in the baseline study, 801 have been included in the follow-up in November 2020. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 and its variants in Ischgl was compared to the incidence in similar municipalities in Tyrol until April 2021. Findings For the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9-54.9) to 45.4% (95% CI 42.0-49.0). Median antibody concentrations dropped considerably (5.345, 95% CI 4.833 - 6.123 to 2.298, 95% CI 2.141 - 2.527) but antibody avidity increased (17.02, 95% CI 16.49 - 17.94 to 42.46, 95% CI 41.06 - 46.26). Only one person had lost detectable antibodies and T cell responses. In parallel to this persistent immunity, we observed that Ischgl was relatively spared, compared to similar municipalities, from the prominent second COVID-19 wave that hit Austria in November 2020. In addition, we used sequencing data to show that the local immunity acquired from wild-type infections also helped to curb infections from variants of SARS-CoV-2 which spread in Austria since January 2021. Interpretation The relatively high level of seroprevalence (40-45%) in Ischgl persisted and might have been associated with the observed protection of Ischgl residents against virus infection during the second COVID-19 wave as well as against variant spread in 2021. Funding Funding was provided by the government of Tyrol and the FWF Austrian Science Fund.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Austria , COVID-19/virology , Cross-Sectional Studies , Europe , Female , Follow-Up Studies , Humans , Male , Seroepidemiologic Studies
3.
Lancet Respir Med ; 9(8): 863-872, 2021 08.
Article in English | MEDLINE | ID: covidwho-1340915

ABSTRACT

BACKGROUND: SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin-angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. METHODS: ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. FINDINGS: Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66-80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00-2·00) vs 1·00 (0·00-3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00-9·25] vs 3·50 [0·00-23·50]; p=0·040), mean SOFA score (0·00 [0·00-0·31] vs 0·12 [0·00-0·78]; p=0·040), and 30-day SOFA score (0·00 [10-90th percentile, 0·00-1·20] vs 0·00 [0·00-24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. INTERPRETATION: Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. FUNDING: Austrian Science Fund and German Center for Cardiovascular Research.


Subject(s)
Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , COVID-19 , Hypertension , Renin-Angiotensin System , SARS-CoV-2 , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Area Under Curve , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/therapy , Female , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Male , Middle Aged , Organ Dysfunction Scores , Outcome and Process Assessment, Health Care , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Risk Adjustment/methods , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Severity of Illness Index , Withholding Treatment/statistics & numerical data
4.
J Intern Med ; 291(1): 101-107, 2022 01.
Article in English | MEDLINE | ID: covidwho-1258958

ABSTRACT

BACKGROUND: Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS-CoV-2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS-CoV-2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow-up of the pandemic. METHOD: Cohort study using data from the UK Biobank during the SARS-CoV-2 pandemic. Baseline Lp(a) was compared between SARS-CoV-2 positive patients and the population controls. RESULTS: SARS-CoV-2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS-CoV-2 positive patients (n = 6937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS-CoV-2 infection modified the association with a steeper increase in risk for infected patients (interaction p-value = 0.03). Although SARS-CoV-2 positive patients had a five-times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a). CONCLUSIONS: SARS-CoV-2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a).


Subject(s)
COVID-19/diagnosis , Lipoprotein(a)/blood , Myocardial Ischemia/epidemiology , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Thromboembolism/epidemiology , Adult , Aged , COVID-19/blood , COVID-19 Nucleic Acid Testing , Case-Control Studies , Cohort Studies , Female , Humans , Intensive Care Units , Male , Middle Aged , Risk Factors , SARS-CoV-2/genetics , Thromboembolism/etiology
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