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1.
Front Immunol ; 13: 817829, 2022.
Article in English | MEDLINE | ID: covidwho-1902978

ABSTRACT

Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent plasma is associated with improved clinical outcomes in patients with Covid-19.In this systematic review and meta-analysis, we searched randomized controlled trials investigating the use of convalescent plasma in patients with Covid-19 in Medline, Embase, Web of Science, Cochrane Library, and medRxiv from inception to October 17th, 2021. Two reviewers independently extracted the data. The primary efficacy outcome was all-cause mortality. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. This study was registered with PROSPERO, CRD42021284861. Of the 8874 studies identified in the initial search, sixteen trials comprising 16 317 patients with Covid-19 were included. In the overall population, the all-cause mortality was 23.8% (2025 of 8524) with convalescent plasma and 24.4% (1903 of 7769) with standard of care (risk ratio (RR) 0.97, 95% CI 0.90-1.04) (high-certainty evidence). All-cause mortality did not differ in the subgroups of noncritically ill (21.7% [1288 of 5929] vs. 22.4% [1320 of 5882]) and critically ill (36.9% [518 of 1404] vs. 36.4% [455 of 1247]) patients with Covid-19. The use of convalescent plasma in patients who tested negative for anti-SARS-CoV-2 antibodies at baseline was not associated with significantly improved survival (RR 0.94, 95% CI 0.87-1.02). In the overall study population, initiation of mechanical ventilation (RR 0.97, 95% CI 0.88-1.07), time to clinical improvement (HR 1.09, 95% CI 0.91-1.30), and time to discharge (HR 0.95, 95% CI 0.89-1.02) were similar between the two groups. In patients with Covid-19, treatment with convalescent plasma, as compared with control, was not associated with lower all-cause mortality or improved disease progression, irrespective of disease severity and baseline antibody status. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021284861).


Subject(s)
COVID-19/therapy , SARS-CoV-2 , Critical Illness , Humans , Immunization, Passive , Respiration, Artificial
2.
Vaccine ; 40(31): 4090-4097, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1867869

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. METHODS: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. RESULTS: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. CONCLUSIONS: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands).


Subject(s)
COVID-19 , Clinical Trials as Topic , Patient Participation , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Child , Europe/epidemiology , Humans , Registries , Volunteers
3.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-333367

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the key role that vaccines play against infectious diseases. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE’s Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. Methods: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. Results: As of January 2022, the questionnaire is available in 9 countries and 11 languages. Up to date, more than 35,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched 13,719 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. Conclusion: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 9 countries. To date, more than 13,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 6 additional countries.

4.
Microbiol Spectr ; 10(1): e0202921, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1673365

ABSTRACT

The objective of our study was to evaluate the sensitivity and specificity of rapid antigen detection tests versus those of reverse transcriptase PCR (RT-PCR) using oral, anterior nasal, and nasopharyngeal swabs. The underlying prospective, diagnostic case-control-type accuracy study included 87 hospitalized and nonhospitalized participants in a positive and a negative sample cohort between 16 March and 14 May 2021 in two hospitals in Vienna. SARS-CoV-2 infection status was confirmed by RT-PCR. Participants self-performed one oral and one anterior nasal swab for the rapid antigen test, immediately followed by two nasopharyngeal swabs for the rapid antigen test and RT-PCR by the investigator. Test results were read after 15 min, and participants completed a questionnaire in the meantime. Test parameters were calculated based on the evaluation of 87 participants. The overall sensitivity of rapid antigen detection tests versus that of RT-PCR with oral, anterior nasal, and nasopharyngeal samples was 18.18% (95% confidence interval [CI] 8.19% to 32.71%), 63.04% (95% CI 47.55% to 76.79%), and 73.33% (95% CI 58.06% to 85.4%), respectively. All sampling methods had a test specificity of 100% regardless of the cycle threshold (CT) value. Rapid antigen detection tests using self-collected anterior nasal swabs proved to be as sensitive as and more tolerable than professionally collected nasopharyngeal swabs for CT values up to 30 determined by RT-PCR. This finding illustrates the reliability of tests obtained by adequate self-collected anterior nasal specimen. Sensitivity was dependent upon the CT value for each sampling method. While the main advantage of rapid antigen detection tests is the immediate availability of results, PCR should be preferred in crucial settings wherever possible. IMPORTANCE Rapid antigen detection devices for SARS-CoV-2 represent a valuable tool for monitoring the spread of infection. However, the reliability of the tests depends largely on the test performance and the respective sampling method. Nasopharyngeal swabs mark the gold standard for sample collection in suspected respiratory tract infections but are unsuitable for widespread application, as they must be performed by medically trained personnel. With the underlying study, the head-to-head test performance and the usability of self-collected samples for SARS-CoV-2 detection using rapid antigen detection devices were evaluated. The results confirm similar sensitivity of self-collected anterior nasal swabs to that of professionally collected nasopharyngeal swabs for patients with a CT of < 30 determined by RT-PCR.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , Mouth/virology , Nasopharynx/virology , Nose/virology , SARS-CoV-2/isolation & purification , Adult , Aged , Aged, 80 and over , Antigens, Viral/analysis , COVID-19/virology , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Prospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity , Young Adult
5.
Ann Rheum Dis ; 81(5): 687-694, 2022 05.
Article in English | MEDLINE | ID: covidwho-1625022

ABSTRACT

OBJECTIVES: SARS-CoV-2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. METHODS: In this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4. RESULTS: Seroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed. CONCLUSIONS: This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , RNA, Messenger , Seroconversion , Vaccination , Vaccines, Synthetic
6.
Clin Pharmacol Ther ; 111(3): 614-623, 2022 03.
Article in English | MEDLINE | ID: covidwho-1549189

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. It has been hypothesized that higher-dose anticoagulation, including therapeutic-dose and intermediate-dose anticoagulation, is superior to prophylactic-dose anticoagulation in the treatment of COVID-19. This meta-analysis evaluated the efficacy and safety of higher-dose anticoagulation compared with prophylactic-dose anticoagulation in patients with COVID-19. Ten randomized controlled open-label trials with a total of 5,753 patients were included. The risk of death and net adverse clinical events (including death, thromboembolic events, and major bleeding) were similar between higher-dose and prophylactic-dose anticoagulation (risk ratio (RR) 0.96, 95% CI, 0.79-1.16, P = 0.66 and RR 0.87, 95% CI, 0.73-1.03, P = 0.11, respectively). Higher-dose anticoagulation, compared with prophylactic-dose anticoagulation, decreased the risk of thromboembolic events (RR 0.63, 95% CI, 0.47-0.84, P = 0.002) but increased the risk of major bleeding (RR 1.76, 95% CI, 1.19-2.62, P = 0.005). The risk of death showed no statistically significant difference between higher-dose anticoagulation and prophylactic-dose anticoagulation in noncritically ill patients (RR 0.87, 95% CI, 0.50-1.52, P = 0.62) and in critically ill patients with COVID-19 (RR 1.04, 95% CI, 0.93-1.17, P = 0.5). The risk of death was similar between therapeutic-dose vs. prophylactic-dose anticoagulation (RR 0.92, 95% CI 0.69-1.21, P = 0.54) and between intermediate-dose vs. prophylactic-dose anticoagulation (RR 1.01, 95% CI 0.63-1.61, P = 0.98). In patients with markedly increased d-dimer levels, higher-dose anticoagulation was also not associated with a decreased risk of death as compared with prophylactic-dose anticoagulation (RR 0.86, 95% CI, 0.64-1.16, P = 0.34). Without any clear evidence of survival benefit, these findings do not support the routine use of therapeutic-dose or intermediate-dose anticoagulation in critically or noncritically ill patients with COVID-19.


Subject(s)
Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Critical Illness , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage/chemically induced , Humans , Thromboembolism/drug therapy , Thromboembolism/prevention & control , Treatment Outcome
8.
Lancet Respir Med ; 9(7): e59, 2021 07.
Article in English | MEDLINE | ID: covidwho-1337047
9.
Eur J Clin Pharmacol ; 77(Suppl 1): 1-42, 2021 06.
Article in English | MEDLINE | ID: covidwho-1333059
10.
Eur J Clin Pharmacol ; 77(Suppl 1): 1-42, 2021 06.
Article in English | MEDLINE | ID: covidwho-1333058
11.
Eur J Clin Pharmacol ; 77(Suppl 1): 1-42, 2021 06.
Article in English | MEDLINE | ID: covidwho-1333057
12.
Eur J Clin Pharmacol ; 77(Suppl 1): 1-42, 2021 06.
Article in English | MEDLINE | ID: covidwho-1333056
17.
Clin Pharmacokinet ; 59(10): 1195-1216, 2020 10.
Article in English | MEDLINE | ID: covidwho-679744

ABSTRACT

There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid and comprehensive review of relevant pharmacological evidence, focusing on (1) the pharmacokinetics (PK) of potential antiviral therapies; (2) coronavirus-specific pharmacodynamics (PD); (3) PK and PD interactions between proposed combination therapies; (4) pharmacology of major supportive therapies; and (5) anticipated drug-drug interactions (DDIs). We found promising in vitro evidence for remdesivir, (hydroxy)chloroquine and favipiravir against SARS-CoV-2; potential clinical benefit in SARS-CoV-2 with remdesivir, the combination of lopinavir/ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against Middle East Respiratory Syndrome (MERS) for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials assessing patient-centred outcomes remain imperative and clinical data have already reduced expectations with regard to some drugs. Any therapy should be used with caution in the light of potential drug interactions and the uncertainty of optimal doses for treating mild versus serious infections.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Analgesics/pharmacology , Anticoagulants/pharmacology , Antiviral Agents/pharmacokinetics , Betacoronavirus , COVID-19 , Coronavirus Infections/physiopathology , Dose-Response Relationship, Drug , Drug Interactions , Extracorporeal Membrane Oxygenation/methods , Humans , Hypnotics and Sedatives/pharmacology , Pandemics , Pneumonia, Viral/physiopathology , Renal Replacement Therapy/methods , SARS-CoV-2 , Therapeutic Index, Drug
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