scholarly journals Casirivimab and imdevimab as investigational monoclonal antibodies for COVID-19 patients – review of the literature

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gabriela Reka ◽  
Angelika Pawlak ◽  
Piotr Machowiec ◽  
Marcela Maksymowicz ◽  
Halina Piecewicz-Szczesna
Keyword(s):  
Monoclonal Antibodies ◽  
Viral Load ◽  
Animal Studies ◽  
Serum Antibody ◽  
High Viral Load ◽  
Supplemental Oxygen ◽  
Low Grade ◽  
Treatment Resistant ◽  
Human Igg1 ◽  
Antibody Cocktail

Abstract Casirivimab and imdevimab (REGN-COV-2) are investigational monoclonal antibodies approved in November 2020 by the Food and Drug Administration for emergency use in mild and moderate COVID-19. These two noncompeting human IgG1 monoclonal antibodies can target the receptor-binding domain of the spike protein of SARSCoV-2, prevent its entry into human cells, and reduce viral load. The antibodies can be administered intravenously for mild-to-moderate COVID-19 patients who do not require hospitalization and supplemental oxygen. The purpose of the study is to review the latest available data on COVID-19 treatment using casirivimab and imdevimab. According to recent preclinical studies, the antibody cocktail presents optimal antiviral strength and has the potential to minimize the chances of the virus escaping. It was shown in animal studies that the cocktail reduces the pathological consequences caused by viruses, decreases the number of viruses in the respiratory system, and reduces lung titers and pneumonia symptoms. Casirivimab and imdevimab as a cocktail also prevents the rapid appearance of treatment-resistant mutants. In the clinical trial, REGN-COV-2 decreased viral load, particularly in patients with a non-initiated immune response (serum antibody-negative) and with high viral load at baseline. The adverse effects were comparable in the combined REGN-COV2 dose groups (2.4 g and 8.0 g), as well as in the placebo group. The cocktail caused few and mainly low-grade toxic effects. Casirivimab and imdevimab seem to be effective and safe antiviral therapy for nonhospitalized patients with COVID-19. Further observations and research are extremely necessary to assess the efficacy, security and indications in a wider group of patients.

scholarly journals REGEN-COV Antibody Cocktail in Outpatients with Covid-19

2021 ◽  
Author(s):  
David Weinreich ◽  
Sumathi Sivapalasingam ◽  
Thomas Norton ◽  
Shazia Ali ◽  
Haitao Gao ◽  
...  
Keyword(s):  
Viral Load ◽  
Relative Risk ◽  
Phase 1 ◽  
Serum Antibody ◽  
Weighted Average ◽  
Baseline Viral Load ◽  
Double Blind ◽  
Group 2 ◽  
Antibody Cocktail ◽  
Group 1

Background: REGEN-COV (casirivimab and imdevimab) antibody cocktail reduced SARS-CoV-2 viral load in descriptive analyses of the first 275 Covid-19 outpatients in the phase 1/2 portion of an ongoing double-blind, seamless phase 1/2/3 trial. Methods: This final analysis of the phase 1/2 portion includes 799 patients: 275 (group-1) and 524 (group-2). Patients were randomized (1:1:1) to placebo, 2400mg REGEN-COV, or 8000mg REGEN-COV, and characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive/negative). Efficacy was assessed in patients with a positive baseline RT-qPCR result; safety was assessed in all treated patients. Prespecified hierarchical analyses of virologic endpoints in group-2 were performed to confirm previously reported descriptive analyses from group-1. The proportion of patients with ≥1 Covid-19-related medically-attended visit (MAV) through day 29 was assessed in group-1+2. Results: Time-weighted average reduction in viral load (log10 copies/ml) through day 7 was significantly greater with REGEN-COV (combined 2400mg+8000mg dose groups) versus placebo in patients with baseline viral load >107 copies/ml (prespecified primary endpoint): -0.68 (95% CI, -0.94 to -0.41; P<0.0001). This reduction was -0.73 (P<0.0001) in serum antibody-negative patients and -0.36 (P=0.0003) in the overall population. Proportions of patients with ≥1 Covid-19-related MAV were 2.8% (12/434) with REGEN-COV versus 6.5% (15/231) with placebo (P=0.024; relative risk reduction=57%), with greater relative risk reductions in MAVs in patients with ≥1 risk factor for hospitalization (71%). Adverse events were similar across groups. Conclusions: REGEN-COV treatment of outpatients significantly reduced SARS-CoV-2 viral load and Covid-19-related medically-attended visits. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.)

scholarly journals Integrative and episomal forms of genotype 16 of human papillomavirus in patients with cervical intraepithelial neoplasia and cervical cancer

2016 ◽  
Vol 61 (6) ◽  
pp. 270-274 ◽  
Author(s):  
M. K. Ibragimova ◽  
M. M. Tsyganov ◽  
I. V. Karabut ◽  
O. N. Churuksaeva ◽  
O. N. Shpileva ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
High Viral Load ◽  
Low Grade ◽  
Squamous Intraepithelial Lesion ◽  
Comprehensive Survey ◽  
Intraepithelial Lesion

The study involved 500 patients with LSIL (low grade squamous intraepithelial lesion), HSIL (high grade squamous intraepithelial lesion), stage I-IV cervical cancer, infected with human papillomavirus (HPV), as well as 235 women without pathological changes in cervical mucosa. The comprehensive survey included colposcopy, cytological and histological analysis, detection and genotyping of high-risk human papillomavirus. Viral load and physical status of HPV16 DNA was evaluated in cases of mono-infection (n = 148). The prevalence of virus-positive cases among the patients with LSIL/NSIL, cervical cancer patients and healthy women was 69.2%, 76.7% and 51.9%, respectively. An association between the severity of disease and high viral load was revealed. The frequency of integrated DNA was strongly increased in patients with a high viral load. The frequency of episomal forms was either reduced or not detecteable in patients with high viral load as compared to patients with low viral load. It is reasonable to suggest that a high HPV16 viral load may cause an increase in the frequency of integration of virus DNA into the cellular/host genome. This suggests that a high HPV16 viral load may be considered as a risk factor for prognosis of cervical intraepithelial neoplasia and cervical cancer.

scholarly journals Analysis of Serological Variability and Hierarchical Distribution of Rice Yellow Mottle Sobemovirus Isolates in Northern Nigeria

2015 ◽  
Vol 37 ◽  
pp. 1-9 ◽  
Author(s):  
G. Alkali ◽  
M.D. Alegbejo ◽  
B.D. Kashina ◽  
O.O. Banwo
Keyword(s):  
Monoclonal Antibodies ◽  
Viral Load ◽  
High Viral Load ◽  
Epidemiological Studies ◽  
Mottle Virus ◽  
Rice Yellow Mottle Virus ◽  
Northern Nigeria ◽  
Hierarchical Analysis ◽  
Immunological Profile ◽  
Yellow Mottle

A panel of four monoclonal antibodies (MAbs) was used to study the immunological profile of Rice yellow mottle virus (RYMV) genus Sobemovirus. Serological profiles of 35 representative isolates of RYMV from Borno, Gombe, Kaduna, Kano, Niger, Sokoto and Zamfara states in Northern Nigeria. All the RYMV isolates were classified into three major serogroups (SG1, SG2 and SG3) and further separated into six subgroups (Sg1a, Sg1b, Sg2a, Sg2b, Sg3a and Sg3b). The results demonstrate a significant serological variability among RYMV isolates in Northern Nigeria. The hierarchical analysis of the serological profiles data revealed high viral load in Kano, Kaduna and Gombe states, these show they are suitable locations for strategic RYMV diagnostic and field epidemiological studies

scholarly journals Monoclonal Antibody Cocktail therapy for COVID-19: A Pharmacological innovation

2021 ◽  
Vol 10 (2) ◽  
pp. 103-105
Author(s):  
Jared Robinson ◽  
Indrajit Banerjee
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
International Health ◽  
The Novel ◽  
Multifaceted Approach ◽  
Mortality And Morbidity ◽  
Viral Shedding ◽  
Human Igg1 ◽  
Ongoing Phase ◽  
Antibody Cocktail

The novel SARS-CoV-2 infection has ripped through international health systems and protocols causing unprecedented mortality, morbidity and global trade deficits amounting to billions. Various monoclonal antibodies have been proposed for use in the treatment of COVID-19 infections. One such drug is LY-CoV555 which in an ongoing phase two trial study conducted by Chen P et al, showed to have an elimination of 99.97% of the viral RNA. The monoclonal antibody 47D11 discovered by Wang et al, binds to SARS-CoV-2. The 47D11 has been reconfigured into a human IgG1 isotope. It has shown that the 47D11 mAb effectively neutralizes the SARS-COV-2 virus. The stance and development however for the treatment of COVID-19 with monoclonal antibodies has shifted from a monotherapy to a so-called monoclonal antibody “cocktail” therapy. REGN-COV2 is such a cocktail developed with the use of two monoclonal antibodies REGN10987 and REGN10933 which have subsequently been named Imdevimab and Casirivimab. REGN-COV2 is currently under study in four phase 2 and 3 trial studies. These studies are multicentric in nature and are being conducted to evaluate the drug’s efficacy, dosing and clinical use as compared to the placebo. The mechanism of action of such monoclonal antibodies is related chiefly to the inhibition of the virus’s ability to perform its invasion and multiplication within the human body. The severity coupled with the sheer novelty of the SARSCoV-2 virus demands the use of newer therapies to both decrease the mortality and morbidity in patients suffering from the infection. The use of a combination of monoclonal antibodies is thereby well established and evident to both decrease the viral infection load, but is also useful in disrupting the virus’s life cycle and thus decreases the replication and viral shedding. It is therefore poignant that a combination of monoclonal antibodies, a “cocktail” therapy is employed so as to attack the virus at its various stages and thus this multifaceted approach may enhance the patient’s prognosis.

Diffuse Large B-Cell Lymphomas (DLBCL) with Hepatitis-C Virus (HCV) Infection: Incidence, Clinical Outcome and Preliminary Results of Antiviral Treatments (AVT) after Chemotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2442-2442
Author(s):  
Pellegrino Musto ◽  
Stefano Luminari ◽  
Amalia De Renzo ◽  
Marcello Persico ◽  
Emilio Iannitto ◽  
...  
Keyword(s):  
Viral Load ◽  
Liver Biopsy ◽  
Clinical Outcome ◽  
High Viral Load ◽  
Hcv Infection ◽  
Low Grade ◽  
Virus Clearance ◽  
Long Term Follow Up ◽  
Remission Phase ◽  
Work Up

Abstract A possible relationship between HCV and some sub-types of low-grade lymphomas (in particular, immunocytomas and nodal/extranodal marginal lymphomas) has been suggested. In these patients, AVT has shown to be effective in inducing neoplastic regression without chemotherapy (CT). In the present study we aimed to define epidemiological, clinical and therapeutic issues in DLBCL with concomitant HCV infection. We evaluated the incidence of HCV infection in 881 consecutive Italian patients with DLBCL (676 of whom collected by GISL - Gruppo Italiano Studio Linfomi, and 205 by ISS - Istituto Superiore di Sanità), in whom HCV determination was available. We found that 105 out of them (11.9%) were HCV+ve. We also looked at the clinical outcome of 61 patients, who had complete clinical and laboratory work-up and long term follow-up. With respect to a cohort of comparable historical controls without HCV infection, HCV+ve DLBCL showed older age (62 vs 48 years, p < 0.03), more frequently signs of liver damage (59% vs 8%, p < 0.001) and presence of monoclonal gammopathy (17% vs 3%, p < 0.05), increased rate of autoimmune disorders (19% vs 3 %, p < 0.02) and extranodal localizations (65.3% vs 35%, p < 0.04), including, in particular, liver, spleen, and other unusual sites (esophagous, vagina), often as primitive disease. First line CT for HCV+ve DLBCL. mainly consisted of classic/modified CHOP+/−rituximab or PROMACE-CytaBOM regimens. Response rate (complete + partial remission) was not different, approaching 60% in both groups. Six-year overall survival (OS) was also similar (62% for HCV+ve and 65% for HCV−ve DLBCL, p 0.67). However, during the first two years, there was a worse trend for HCV+ve patients with increased ALT levels, high viral load (> 800.000 IU RNA viral copies) and evidence of active hepatitis or cirrhosis at liver biopsy. Finally, we evaluated the possible role of AVT given after standard CT in HCV+ve DLBCL. Preliminary data available from 37 patients who have received at least three months of interferon (alpha or pegylated) +/− ribavirin in remission phase, indicate that such a sequential treatment is feasible, may induce complete virus clearance and may be associated with prolonged remission duration, without affecting, however, OS. In conclusion, about 12% of Italian patients with DBLCL have concomitant HCV infection and show some distinctive clinical and biological characteristics. In absence of liver dysfunction, these subjects should receive standard treatments as their HCV−ve counterparts. Monitoring of viral load and liver biopsy appears also to be useful for an appropriate management. A sequence of standard CT followed by AVT is a feasible approach which warrants to be further investigated.

Update in management of hepatitis B in pregnancy and prevention of mother to child hepatitis B transmission

2018 ◽  
Vol 1 (3) ◽  
pp. 1-8
Author(s):  
Naichaya Chamroonkul
Keyword(s):  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
High Viral Load ◽  
World Population ◽  
Hepatitis B Infection ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
Mother To Child

Even with two decades of widespread using hepatitis B vaccination, chronic hepatitis B remains a major global health problem. In Thailand, the prevalence of chronic hepatitis B infection was down from 8 - 10% in last decade to 5% recently. Failure to control mother to child transmission is one of the important barriers to the total elimination of hepatitis B infection from world population. In the majority, vertical transmission can be prevented with a universal screening program, immunoprophylaxis by administration of hepatitis B vaccine and hepatitis B immunoglobulin (HBIg) for babies born to mothers with HBV. However, in mothers with a high viral load, the chance of immunoprophylaxis failure remains high. To date, there are standard recommendations by all international liver societies including AASLD, EASL and APASL suggest introducing an antiviral agent during the third trimester to CHB pregnant women with a high viral load. Previous US FDA pregnancy category B agents such as Tenofovir and Telbivudine are allowed through all trimesters of pregnancy and are effective for prevention of mother to child transmission. Breastfeeding for patients who receive antiviral agents can be allowed after a risk-benefit discussion with the patient and family.

scholarly journals Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide

Perfusion ◽  
2021 ◽  
pp. 026765912098653
Author(s):  
Hafiz Naderi ◽  
Shaun Robinson ◽  
Martin J Swaans ◽  
Nina Bual ◽  
Wing-See Cheung ◽  
...  
Keyword(s):  
Viral Load ◽  
Potential Role ◽  
Assessment Tool ◽  
High Viral Load ◽  
First Line ◽  
Scanning Time ◽  
Contagious Disease ◽  
Core Dataset ◽  
Clinical Questions

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

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