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1.
Vox Sang ; 117(5): 641-646, 2022 May.
Article in English | MEDLINE | ID: covidwho-1840539

ABSTRACT

COVID-19 convalescent plasma (CCP) was among the few frontline therapies used to treat COVID-19. After large randomized controlled trials (RCTs) relying on late use in hospitalized patients and/or low antibody titres failed to meet their predefined primary endpoint, the infectious disease community reduced usage of CCP in favour of monoclonal antibodies. Consequently, there are CCP stocks at most transfusion centres worldwide, although scattered usage continues. Further, better designed RCTs are also being launched. The urgent question here is: should we use CCP units collected months before given the largely changed viral variant landscape? We review here in vitro evidence that discourages usage of such CCP units against Delta and other variants of concern. CCP collections should be continued in order to update the armamentarium of therapeutics against vaccine breakthrough infections or in unvaccinated patients and is especially relevant in next-generation RCTs.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive
2.
J Clin Virol Plus ; 2(3): 100082, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1821341

ABSTRACT

Given the ongoing COVID19 pandemic, the decline in serological response since dose 2, and the upcoming flu season, COVID19 vaccines will increasingly be administered in combination with vaccines against seasonal pathogens. It is of interest to confirm that concurrent vaccination against influenzavirus has no negative impact on serological response to SARS CoV-2. Anti-Spike IgG and Anti-Receptor Binding Domain (RBD) Neutralizing Antibodies (NAb) in serum  was assessed in 64 immunocompetent healthcare workers (HCW) before and 14 days post the third dose of BNT162b2 vaccine (Comirnaty®, Pfizer/BioNTech) or BNT162b2 plus quadrivalent flu vaccine (Vaxigript Tetra ®Sanofi Pasteur) on the same day. We report here safety and efficacy of combined BNT162b2 and flu vaccine in 64 healthcare workers at a single institution. No differences were found in adverse events or anti-Spike antibody levels.

3.
Emerg Infect Dis ; 28(5): 1083, 2022 May.
Article in English | MEDLINE | ID: covidwho-1809297
4.
Transfusion ; 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1794552

ABSTRACT

BACKGROUND: Novel SARS-CoV-2 variants of concern (VOC) Delta and Omicron are able to escape some monoclonal antibody therapies, making again COVID-19 convalescent plasma (CCP) a potential frontline treatment. STUDY DESIGN/METHODS: In this study, we investigated the kinetics of anti-SARS-CoV-2 neutralizing antibodies (nAbs) against VOCs Delta and Omicron in vaccine breakthrough infected plasma donors. Serum samples from 19 donors were collected at the time of plasma donation and tested for anti-SARS-CoV-2 nAbs (using live authentic VOC viral neutralization test) and IgG (Liaison® SARS-CoV-2 S1/S2 and Liaison® SARS-CoV-2 TrimericS IgG assays, DiaSorin). Measures were correlated with different variables, including the time between last vaccine dose and CCP donation, and time between SARS-COV-2 infection and CCP donation. RESULTS: nAb titers against VOC Delta and Omicron were directly related to the time interval since last vaccine dose to CCP donation, but inversely related to time since COVID19 breakthrough infection. DISCUSSION: SARS-CoV-2 breakthrough infection in vaccinated in donors boosts nAb titers against VOCs Delta and Omicron, but such titers decay shortly after infection. Therefore, CCP must be collected early after vaccine breakthrough infection.

5.
Life ; 12(5):614, 2022.
Article in English | MDPI | ID: covidwho-1792608

ABSTRACT

Welcome to the Special Issue of Life entitled 'Neutralizing-Antibody-Based Treatments for COVID-19: Achievements and Lessons Learnt for Future Pandemics';[...]

6.
Emerg Infect Dis ; 28(6): 1301-1302, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1789326

ABSTRACT

We report 25 cases of infection with SARS-CoV-2 Omicron variant containing spike protein L452R mutation in northern Lombardy, Italy. Prevalence of this variant was >30% in this region, compared with <0.5% worldwide. Many laboratories are using previously developed L452R-specific PCRs to discriminate Omicron from Delta mutations, but these tests may be unreliable.

7.
Expert Opin Drug Discov ; : 1-16, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1774242

ABSTRACT

INTRODUCTION: The ongoing COVID19 pandemic represents an unprecedented opportunity to test the feasibility of monoclonal antibody (mAb) therapies against respiratory viruses. While many hurdles were easily predictable (e.g. time to develop, scalability, and economic sustainability), mAb cocktails (i.e. the combination of two mAbs) were finally deployed in 2021, one year after the beginning of the pandemic. Of them, the REGN-COV-2 cocktail was likely the most successful experience and contributed at saving lives at the time of the wave sustained by the Delta variant of concern (VOC). AREAS COVERED: Herein, the authors review the preclinical and clinical history of the casirivimab + imdevimab cocktail for the treatment of novel coronavirus infection. The authors furthermore provide the reader with their perspectives on this cocktail including its current place in the treatment armamentarium. EXPERT OPINION: Unfortunately, results from clinical trials highlighted a very limited efficacy in inpatients; furthermore, the current evidence with regards to its lack of effectiveness against the current dominant VOC (omicron) suggests a very limited use of these drugs in the future. In the authors' opinion, this story reminds us of the limitations of mAb therapies in pandemic settings, and of the inferiority of monoclonal versus polyclonal antibody-based therapeutics in such scenarios.

8.
Rev Med Virol ; : e2351, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1772841
10.
Clin Microbiol Rev ; : e0020021, 2022 Mar 09.
Article in English | MEDLINE | ID: covidwho-1736023

ABSTRACT

Convalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light on the mechanisms of action, safety, and efficacy of CP using modern evidence-based medicine approaches. Studies ranging from observational case series to randomized controlled trials (RCTs) have reported highly variable efficacy results for COVID-19 CP (CCP), resulting in uncertainty. We analyzed variables associated with efficacy, such as clinical settings, disease severity, CCP SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antibody levels and function, dose, timing of administration (variously defined as time from onset of symptoms, molecular diagnosis, diagnosis of pneumonia, or hospitalization, or by serostatus), outcomes (defined as hospitalization, requirement for ventilation, clinical improvement, or mortality), CCP provenance and time for collection, and criteria for efficacy. The conflicting trial results, along with both recent WHO guidelines discouraging CCP usage and the recent expansion of the FDA emergency use authorization (EUA) to include outpatient use of CCP, create confusion for both clinicians and patients about the appropriate use of CCP. A review of 30 available RCTs demonstrated that signals of efficacy (including reductions in mortality) were more likely if the CCP neutralizing titer was >160 and the time to randomization was less than 9 days. The emergence of the Omicron variant also reminds us of the benefits of polyclonal antibody therapies, especially as a bridge to the development and availability of more specific therapies.

11.
Vaccines (Basel) ; 10(3)2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1732278

ABSTRACT

During the ongoing COVID-19 pandemic, serology has suffered several manufacturing and budget bottlenecks. Kode technology exposes exogenous antigens on the surface of cells; in the case of red blood cells, modified cells are called kodecytes, making antibody-antigen reactions detectable by the old-fashioned hemagglutination test. In this commentary, we review evidence supporting the utility of SARS-CoV-2 Spike kodecytes for clinical diagnostic purposes and serosurveys in resource-poor settings.

12.
The New Microbiologica ; 44(4):205, 2021.
Article in English | ProQuest Central | ID: covidwho-1696320

ABSTRACT

The SARS-CoV-2 pandemic is ongoing worldwide, causing prolonged pressure on molecular diagnostics. Viral antigen (Ag) assays have several advantages, ranging from lower cost to shorter turnaround time to detection. Given the rare occurrence of low-load viremia, antigen assays for SARSCoV-2 have focused on nasopharyngeal swab and saliva as biological matrices, but their effectiveness must be validated. We assayed here the performances of the novel quantitative Liaison® SARSCoV-2 Ag assay on 119 nasopharyngeal swabs and obtained results were compared with Hologic Panther and Abbott m2000 RT-qPCR. The Ag assay demonstrated a good correlation with viral load, shorter turnaround time, and favorable economics. The best performance was obtained in the acute phase of disease.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310568

ABSTRACT

Human respiratory beta coronavirus are emerging causes for Public Health Emergencies of International Concern (PHEIC). SARS-CoV2 is circulating worldwide since November 2019. We review here the cardiovascular morbidity and mortality in COVID-19, and data supporting the role for dysregulation of the RAS counterregulatory axis due to binding of SARS-CoV2 S protein to ACE2 receptor. Since this counterregulatory axis provides benefits not only on the cardiovascular front but also in acute lung injury, we speculate on potential use of ACE inhibitors and AT1R blockers in critically ill COVID-19 patients, and report current evidences.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310567

ABSTRACT

Convalescent blood product therapy has been introduced since early 1900s to treat emerging infectious disease based on the evidence that polyclonal neutralizing antibodies can reduce duration of viremia. Recent large outbreaks of viral diseases for whom effective antivirals or vaccines are still lacking has revamped the interest in convalescent plasma as life-saving treatments. This review summarizes historical settings of application, and surveys current technologies for collection, manufacturing, pathogen inactivation, and banking, with a focus on COVID-19.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310566

ABSTRACT

We report here the first in vivo selection of a Spike mutation (Q493R) conferring simultaneoius full resistance to both bamlanivimab and etesivimab.

18.
Transfusion ; 62(3): 717-719, 2022 03.
Article in English | MEDLINE | ID: covidwho-1673309
19.
Lancet Respir Med ; 10(3): 226-228, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671370
20.
Antiviral Res ; 198: 105247, 2022 02.
Article in English | MEDLINE | ID: covidwho-1632314

ABSTRACT

Massive usage of antiviral compounds during a pandemic creates an ideal ground for emergence of resistant strains. Remdesivir, a broad-spectrum inhibitor of the viral RNA-dependent RNA polymerase (RdRp), was extensively prescribed under emergency use authorization during the first 18 months of the COVID19 pandemic, before randomized controlled trials showed poor efficacy in hospitalized patients. RdRp mutations conferring resistance to remdesivir are well known from in vitro studies, and the huge SARS-CoV-2 sequencing effort during the ongoing COVID19 pandemic represents an unprecedented opportunity to assess emergence and fitness of antiviral resistance in vivo. We mined the GISAID database to extrapolate the frequency of remdesivir escape mutations. Our analysis reveals very low levels of remdesivir resistance worldwide despite massive usage.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Resistance, Viral/genetics , SARS-CoV-2/genetics , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Drug Repositioning , Genome, Viral/genetics , Humans , Polyproteins/genetics , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , Viral Proteins/genetics
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