scholarly journals COVID-19 Convalescent Plasma Is More Than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1594
Author(s):  
Daniele Focosi ◽  
Massimo Franchini ◽  
Liise-anne Pirofski ◽  
Thierry Burnouf ◽  
DeLisa Fairweather ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Neutralizing Antibodies ◽  
Randomized Clinical Trials ◽  
Neutralizing Antibody ◽  
Causal Link ◽  
Fresh Frozen Plasma ◽  
Post Exposure Prophylaxis ◽  
Fresh Frozen ◽  
Antibody Effects ◽  
Exposure Prophylaxis

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.

scholarly journals A combination of two human neutralizing antibodies prevents SARS-CoV-2 infection in rhesus macaques

2021 ◽  
Author(s):  
Ronald R. Cobb ◽  
Joseph Nkolola ◽  
Pavlo Gilchuk ◽  
Abishek Chandrashekar ◽  
Robert V. House ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
Post Exposure Prophylaxis ◽  
Human Mabs ◽  
Viral Neutralization ◽  
Exposure Prophylaxis ◽  
Human Primate

Human monoclonal antibody (mAb) treatments are promising for COVID-19 prevention, post-exposure prophylaxis, or therapy. However, the titer of neutralizing antibodies required for protection against SARS-CoV-2 infection remains poorly characterized. We previously described two potently neutralizing mAbs COV2-2130 and COV2-2381 targeting non-overlapping epitopes on the receptor-binding domain of SARS-CoV-2 spike protein. Here, we engineered the Fc-region of these mAbs with mutations to extend their persistence in humans and reduce interactions with Fc gamma receptors. Passive transfer of individual or combinations of the two antibodies (designated ADM03820) given prophylactically by intravenous or intramuscular route conferred virological protection in a non-human primate (NHP) model of SARS-CoV-2 infection, and ADM03820 potently neutralized SARS-CoV-2 variants of concern in vitro. We defined 6,000 as a protective serum neutralizing antibody titer in NHPs against infection for passively transferred human mAbs that acted by direct viral neutralization, which corresponded to a concentration of 20 microgram/mL of circulating mAb.

Chapter 14: Prevention: vaccines and immunoglobulins

2021 ◽  
Author(s):  
Eva-Maria Pöllabauer ◽  
Herwig Kollaritsch
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Western Europe ◽  
Surrogate Marker ◽  
Booster Vaccination ◽  
Post Exposure Prophylaxis ◽  
Pediatric Formulation ◽  
The One ◽  
Exposure Prophylaxis

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao. All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

scholarly journals Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study

2021 ◽  
Vol 10 (24) ◽  
pp. 5891
Author(s):  
Marina Sánchez-Rico ◽  
Frédéric Limosin ◽  
Raphaël Vernet ◽  
Nathanaël Beeker ◽  
Antoine Neuraz ◽  
...  
Keyword(s):  
Observational Study ◽  
Randomized Clinical Trials ◽  
Acid Sphingomyelinase ◽  
Potential Usefulness ◽  
Sensitivity Analyses ◽  
Post Exposure Prophylaxis ◽  
Multivariable Logistic Regression Model ◽  
Double Blind ◽  
Multicenter Observational Study ◽  
Exposure Prophylaxis

(1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients’ characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29–0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

scholarly journals Effectiveness and Safety of an Intravenous Immune Globulin (IVIG) Preparation in Post-exposure Prophylaxis (PEP) Against Measles in Infants

2021 ◽  
Vol 9 ◽  
Author(s):  
Benno Kohlmaier ◽  
Heidemarie Holzmann ◽  
Karin Stiasny ◽  
Manuel Leitner ◽  
Christoph Zurl ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Active Immunization ◽  
Ivig Treatment ◽  
Post Exposure Prophylaxis ◽  
Igg Antibodies ◽  
Post Exposure ◽  
Ivig Preparation ◽  
Specific Igg ◽  
Exposure Prophylaxis ◽  
Maternal Igg

Background: Administration of measles virus (MV)-specific IgG as post-exposure prophylaxis (PEP) is known to effectively prevent measles. Since the introduction of active immunization against measles, the levels of MV-specific IgG antibodies in the population have dropped. Therefore, the concentration of MV-specific antibodies in immunoglobulin products derived from human plasma donors has declined as the proportion of vaccinated donors has increased. Literature on the effectiveness of PEP with current available immunoglobulins is limited. Here we examine the effectiveness of 400 mg/kg intravenous immunoglobulin (IVIG) (IgVena®, Kendrion) as PEP in infants during a measles outbreak in Austria, 2019.Methods: After exposure to a highly contagious measles patient, identified infants were evaluated for eligibility for IVIG PEP. Infants were tested for measles maternal antibodies, if the result was expected to be available within 72 h after exposure. IVIG was administered to eligible infants with negative maternal IgG antibody levels (n = 11), infants with protective levels but result beyond 72 h (n = 2) and infants not tested for maternal IgG antibodies (n = 52). Telephone enquiries were made asking for measles infection. Effectiveness was calculated using exact logistic regression. Samples of four out of seven used IVIG batches were tested for MV-neutralizing antibody capacity.Results: In 63 (96.9%) of 65 infants PEP with IVIG was administered. The parents of two infants declined IVIG PEP. None of the infants with IVIG PEP got measles or symptoms suggestive for measles, but both infants who did not receive PEP were infected. Effectiveness of IVIG PEP was calculated to be 99.3% (CI 95%: 88.7–100%). No serious adverse event of IVIG treatment was observed. The investigation on MV-neutralizing antibody capacity showed a geometric mean titer ranging from 10.0 to 12.7 IU/ml, resulting in a 1.57–2.26-fold higher concentration than postulated as minimum level for immunity.Conclusions: Our findings suggest that the used IVIG preparation provided an at least non-inferior protection rate compared to IVIG preparations derived from donors before the global introduction of standard active immunization against measles.

scholarly journals Characteristics of high titer convalescent plasma and antibody dynamics following administration in patients with severe COVID-19

2021 ◽  
Author(s):  
Emma D Bainbridge ◽  
Priscilla Y Hsue ◽  
Jonathan H Esensten ◽  
Kara L Lynch ◽  
Carolyn M Hendrickson ◽  
...  
Keyword(s):  
High Titer ◽  
Neutralizing Antibody ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
Antibody Levels ◽  
Antibody Dynamics ◽  
Frozen Plasma ◽  
Selection Of ◽  
Donor Plasma

Abstract We characterized the antibody composition of COVID-19 convalescent plasma (CCP) and the immunologic responses of hospitalized COVID-19 patients after receiving CCP or non-immune fresh frozen plasma (FFP). Despite selection of CCP with significantly higher total IgG than recipients, neutralizing antibody levels did not differ between donor plasma and CCP recipients.

Chapter 14: Prevention – Vaccines + Immunoglobulins

2019 ◽  
Author(s):  
Eva-Maria Pöllabauer ◽  
Herwig Kollaritsch
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Western Europe ◽  
Surrogate Marker ◽  
Booster Vaccination ◽  
Post Exposure Prophylaxis ◽  
Pediatric Formulation ◽  
The One ◽  
Exposure Prophylaxis

• Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. • The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao • All TBE vaccines except the one from China have similar but not identical immunization sched-ules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir a rapid immunization schedules is also licensed. The Chinese vaccine is giv-en with 2 primary doses 2 weeks apart followed by annual boosters. • All vaccines induce significant immune responses. In the absence of a formal correlate of pro-tection, the presence of neutralizing antibodies is used as a surrogate marker for protection. • Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. • An effectiveness of approximately 99% (years 2000–2006) and 98,7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccina-tion uptake. • Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. • Both - FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

scholarly journals Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

HIV Medicine ◽  
2020 ◽  
Author(s):  
I Fernández ◽  
E. Lazzari ◽  
A. Inciarte ◽  
V. Diaz‐Brito ◽  
A. Milinkovic ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Exposure Prophylaxis

scholarly journals Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19

2020 ◽  
Author(s):  
SARAH M LOFGREN ◽  
Melanie R Nicol ◽  
Ananta S Bangdiwala ◽  
Katelyn A Pastick ◽  
Elizabeth C Okafor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Side Effect ◽  
Randomized Clinical Trials ◽  
Safety Data ◽  
Post Exposure Prophylaxis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Gastrointestinal Side Effects ◽  
Exposure Prophylaxis

Introduction: Use of hydroxychloroquine in hospitalized patients with COVID-19, especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from three outpatient randomized clinical trials. Methods: We conducted three randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, post-exposure prophylaxis and early treatment for COVID-19. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. Results: We enrolled 2,795 participants. The median age of research participants was 40 (IQR 34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2,324 (84%) participants reported side effect data, and 638 (27%) reported at least one medication side effect. Side effects were reported in 29% with daily, 36% with twice weekly, 31% with once weekly hydroxychloroquine compared to 19% with placebo. The most common side effects were upset stomach or nausea (25% with daily, 18% with twice weekly, 16% with weekly, vs. 10% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for daily, 16% twice weekly, 12% weekly, vs. 6% for placebo). Two individuals were hospitalized for atrial arrhythmias, one on placebo and one on twice weekly hydroxychloroquine. No sudden deaths occurred. Conclusion: Data from three outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials can safely investigate whether hydroxychloroquine is efficacious for COVID-19.

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