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1.
Journal of Advances in Medical and Biomedical Research ; 30(139):75-85, 2022.
Article in English | EMBASE | ID: covidwho-1822722

ABSTRACT

Novel coronavirus causes the outbreak of COVID-19. There is still no verified treatment regimen against this novel virus;however, different drugs and compounds have been tested against it. Ample proposals have led to a good understanding of pathogenesis and drug efficacy against the novel virus disease. Excess systemic inflammation, which is described as cytokine storm, in the severe cases of COVID-19 can pass through the blood-brain barrier, enter the brain tissue, and activate the microglial cells and oligodenritcytes. Activation of the microglia cells and oligodenritcytes can increase generation of reactive oxygen species in the brain. Excess generation of reactive oxygen species can in turn increase neuro-inflammation in some cases of patients with COVID-19. Treatment of COVID-19 is far from clear. Today, some antiviral drugs such as remdisivir, favipiravir, ribavirin, kaletra, and arbidol are being tested against the disease. Besides these drugs, corticosteroids, anti-malaria drugs (such as chloroquine family), anticoagulants (such as heparin or enoxaparin) are repurposed. In this paper, first we explained the pathogenesis of COVID-19 particles, particularly in the brain. Second, we reviewed recent treatment options up to now, including interferon therapy, convalescent plasma exchange, plasmapheresis, immunoglobin therapy, and use of specified monoclonal anti-bodies in COVID-19 patients.

2.
ACG Case Reports Journal ; 9(3), 2022.
Article in English | EMBASE | ID: covidwho-1822626

ABSTRACT

Liver injury is a common manifestation of coronavirus disease 2019 (COVID-19), with most injuries manifesting as transient mild hepatocellular injury. Cholestatic injury occurs less commonly and is typically mild. Severe cholestatic injury is rare, with only 4 cases reported in the literature. We present a 70-year-old woman with no known liver disease who presented with severe COVID-19 and developed severe cholestatic hepatitis. A liver biopsy was performed demonstrating bile duct injury, uncommonly reported in patients with COVID-19. This complication needs greater awareness because it has been known to cause progressive liver disease requiring transplantation.

3.
Frontiers in Microbiology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822382

ABSTRACT

Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) and T-cell (ELISpot) immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins as well as to human endemic coronavirus (eCoV) peptides in serum from convalescent coronavirus disease 2019 (COVID-19) patients from Tatarstan, Russia. We identified multiple SARS-CoV-2 peptides that were reactive with serum antibodies and T cells from convalescent COVID-19. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Moreover, several SARS-CoV-2 peptides tested negatively correlated with disease severity and lung damage. Cross-reactivity to eCoV peptides was analyzed and found to be lower in COVID-19 compared to controls. In this study, we demonstrate the changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age, gender and previous exposure to eCoVs. These data highlight how humoral immune responses and cytotoxic T cell responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

4.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816892

ABSTRACT

Introduction: The emergence of SARS-CoV-2 virus, which causes COVID-19, is a major global health hazard. Therefore, a comprehensive characterization of the humoral and cellular immune responses to this virus is essential to combat the COVID-19 pandemic. Our goal was to develop reliable methods and tools for the analysis of humoral and cellular B- and T- cell responses, which will facilitate scientific research for prediction of disease progression, long-term immunity and will support vaccine development. Methods: Plasma samples and PBMCs of COVID-19 convalescent and healthy donors were obtained. For the detection of SARS-CoV-2 specific antibodies and identification of antigen-specific B cells, we manufactured recombinant mono-biotinylated protein variants of the Spike (S), Receptor Binding Domain (RBD) and Nucleoprotein (N). To identify antigen-reactive T cells, SARS-CoV-2 peptide pools were synthetized for the S, N and Membrane (M) antigens and used for stimulation. The peptide pools consist of mainly 15-mer peptides having an 11-mer amino acid overlap and thereby overspan a whole protein sequence. Results: To determine the presence of SARS-CoV-2 reactive antibodies a flow-based bead assay using recombinant, mono-biotinylated SARS-CoV-2 antigens loaded onto Streptavidin (SAV)-coated-PMMA beads was set up. The beads were incubated with plasma samples and fluorochrome conjugated anti-human isotype specific antibodies for flow cytometric analysis. All the antigens tested were shown to be suitable for the detection of antibodies to SARS-CoV-2 in COVID-19 convalescent plasma. To assess the feasibility of recombinant antigens for the detection and isolation of antigen-specific B cells, the mono-biotinylated Spike and RBD antigens were tetramerized on fluorochrome-conjugated SAV. These tetramers were used for staining, magnetic enrichment and flow cytometric sorting of B cells specific to SARS-CoV-2 antigens. We were able to demonstrate that our recombinant antigens can be used to assess the presence and enable the phenotyping and isolation of rare antigen-specific B cells. For further characterization of the SARS-CoV-2 reactive T cell immunity PBMCs were short term stimulated with the S, M and N peptide pools. After intracellular staining of IFNg, TNFa, IL-2 and CD154, reactive T cells were detected using flow cytometry. We could demonstrate T cell reactivity towards each peptide pool. However, strengths of T cell responses towards the S, M and N peptide pools were heterogeneous between different COVID-19 convalescent individuals. Conclusion: To support and improve current research activities for the identification and characterization of SARS-CoV-2 reactive humoral and cellular B- and T- cell responses, potent tools and assays were developed. Described here research solutions offer the opportunity to successfully address and contribute to the investigation on healthy and dysfunctional immune reactions towards SARS-CoV-2.

5.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816927

ABSTRACT

Introduction Treatment of B-lineage lymphoma with B-cell depleting immunotherapy causes B-cell aplasia and impairs immune response. Case studies have reported patients treated with anti-CD20 therapy who suffered from persistent Covid-19. We aimed to assess the incidence, risk factors and long-term outcomes of persistent Covid-19 in patients with lymphoma. Patients and methods This retrospective multicentric study was conducted in 16 French hospitals. All adult patients with lymphoma who were admitted for Covid-19 in March and April 2020 were included. Persistent Covid-19 was defined as persisting severe Covid-19 symptoms requiring in-hospital stay for >30 days. Patients who re-experienced severe Covid-19 symptoms after initial improvement, requiring repeated hospitalizations for a total in-hospital length of stay >30 days were added to the persistent Covid-19 cases. Results One hundred eleven patients were included. Thirty days after admission for Covid-19, 24 patients had died, 55 had been definitively discharged from hospital, 31 were still hospitalized and 1 was later rehospitalized for Covid-19 recurrence. The incidence of persistent Covid-19 was 32/111 (29%). Patients with persistent Covid-19 had a median age of 64 years (range, 43-87) and 63% were male. Twenty-two patients (69%) had at least one significant comorbidity. None of the patients with T-cell (n=8) lymphoma or classical Hodgkin's disease (n=8) experienced persistent Covid-19. In the 32 patients with persistent Covid-19, the median time between first admission and final discharge was 58 days (range, 31-235) and the median duration of Covid-19 symptoms was 83 days (range, 32-237). Eight patients received corticosteroids and 9 convalescent plasma: all patients recovered from their symptoms, except one. Overall, 9 patients with persistent Covid-19 died (27%). After a median follow-up of 191 days (range, 3-260), the 6-month overall survival was 69% (95% CI 60-78%) for the whole cohort. In multivariate analysis, administration of anti-CD20 monoclonal antibody within 12 months before admission to hospital for Covid-19 was both associated with decreased overall survival (HR 2.13, 95% CI 1.03-4.44, p = 0.043) and prolonged in-hospital stay (HR 1.97, 95% CI 1.24-3.13, p = 0.004). The two other significant factors associated with decreased overall survival and prolonged in-hospital stay: age ≥ 70 years and refractory or relapsed lymphoma. Conclusion Patients with B-cell non-Hodgkin lymphoma hospitalized for Covid-19 have a high incidence of prolonged evolution of SARS-CoV-2 infection. Administration of anti-CD20 therapy within the last 12 months is one of the main risk factors for longer in-hospital stay and death of Covid-19. The risk of persistent Covid-19 was also higher in patients older than 70 years or with refractory or relapsed disease. These findings may contribute to guide the management of lymphoma patients during the Covid-19 pandemic.

6.
Journal of Clinical and Translational Science ; 2022.
Article in English | EMBASE | ID: covidwho-1815388

ABSTRACT

Introduction. As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring. Methods. The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed. Results. Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial's DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report. Conclusion. It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMB coordination and will help expand these initiatives so DSMBs may make more informed decisions with all available information.

7.
J Med Life ; 15(3):319-327, 2022.
Article in English | PubMed | ID: covidwho-1811949

ABSTRACT

In December 2019, in Wuhan, China, the first cases of infection with SARS-CoV 2 responsible for COVID-19 disease were identified. SARS-CoV 2 was declared a pandemic on March 11, 2020, and since then has attracted the medical world's attention. The threat to humans' health that this emerging pandemic could leave raises awareness on the importance of understanding the mechanisms that underlie the developing conditions. The epidemiology, clinical picture, and pathogenesis of COVID-19 show that this virus presents new strategies to overcome the past defensive medicine. While all the current data has focused on the pulmonary and cardiovascular manifestations, little has been written about the neurological implications of the disease. This review updates new clinical aspects that SARS-CoV 2 expresses in humans by focusing primarily on neurological manifestations. The damage to the nervous system became more apparent - anosmia, ageusia, polyneuritis, meningitis, meningoencephalitis, stroke, acute necrotizing encephalopathy. Oxygen therapy is vital for those in critical health situations. Finally, prevention is the most important element in breaking the epidemiological chain.

8.
Front Cardiovasc Med ; 9:854750, 2022.
Article in English | PubMed | ID: covidwho-1809362

ABSTRACT

In COVID-19 the development of severe viral pneumonia that is coupled with systemic inflammatory response triggers multi-organ failure and is of major concern. Cardiac involvement occurs in nearly 60% of patients with pre-existing cardiovascular conditions and heralds worse clinical outcome. Diagnoses carried out in the acute phase of COVID-19 rely upon increased levels of circulating cardiac injury biomarkers and transthoracic echocardiography. These diagnostics, however, were unable to pinpoint the mechanisms of cardiac injury in COVID-19 patients. Identifying the main features of cardiac injury remains an urgent yet unmet need in cardiology, given the potential clinical consequences. Cardiovascular magnetic resonance (CMR) provides an unparalleled opportunity to gain a deeper insight into myocardial injury given its unique ability to interrogate the properties of myocardial tissue. This endeavor is particularly important in convalescent COVID-19 patients as many continue to experience chest pain, palpitations, dyspnea and exertional fatigue, six or more months after the acute illness. This review will provide a critical appraisal of research on cardiovascular damage in convalescent adult COVID-19 patients with an emphasis on the use of CMR and its value to our understanding of organ damage.

9.
Clin Hemorheol Microcirc ; 2022.
Article in English | PubMed | ID: covidwho-1809306

ABSTRACT

BACKGROUND: Elevated estimated blood viscosity (EBV), derived from hematocrit and globulins, is associated with thrombotic complications, organ failure, and higher mortality in COVID-19 patients. Although informative, EBV does not account for cellular interactions or fibrinogen. OBJECTIVE: Investigate whether patients with acute and recent COVID-19 have altered WBV profiles. METHODS: Cross-sectional study of 58 patients: 15 in the intensive care unit with acute COVID-19, 32 convalescent (9 <  8weeks [W] from acute infection, 23 >  8 W), and 11 controls without COVID-19. WBV was measured at high (300 s-1) and low (5 s-1) shear rates (HSR, LSR) using a scanning capillary viscometer.RESULTSAcute and convalescent patients <  8 W had mean WBV at LSR (16.0 centipoise [cP] and 15.1 cP) and HSR (5.1 cP and 4.7 cP). Mean WBV of convalescent >  8 W and control patients were 12.3 cP and 13.0 cP at LSR, and 4.1 cP and 4.2 cP at HSR. Acute and <  8 W patients had significantly higher WBV at both HSR and LSR compared to patients >  8 W (all p≤0.01). No significant differences in WBV were observed between acute and <  8 W patients, or between patients >  8 W and controls. CONCLUSIONS: Hyperviscosity provides a possible explanation for thrombotic risk in acute and convalescent (<  8 W) patients. These findings have important implications for thromboprophylaxis.

10.
Emerg Infect Dis ; 28(5):1083-1084, 2022.
Article in English | PubMed | ID: covidwho-1809300
11.
International Immunopharmacology ; : 108786, 2022.
Article in English | ScienceDirect | ID: covidwho-1799890

ABSTRACT

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing a global pandemic called COVID-19. Currently, there is no definitive treatment for this emerging disease. Global efforts resulted in developing multiple platforms of COVID-19 vaccines, but their efficacy in humans should be wholly investigated in the long-term clinical and epidemiological follow-ups. Despite the international efforts, COVID-19 vaccination accompanies challenges, including financial and political obstacles, serious adverse effects (AEs), the impossibility of using vaccines in certain groups of people in the community, and viral evasion due to emerging novel variants of SARS-CoV-2 in many countries. For these reasons, passive immunotherapy has been considered a complementary remedy and a promising way to manage COVID-19. These approaches arebased on reduced inflammation due to inhibiting cytokine storm phenomena, immunomodulation,preventing acute respiratory distress syndrome (ARDS), viral neutralization, anddecreased viral load. This article highlights passive immunotherapy and immunomodulation approaches in managing and treating COVID-19 patients and discusses relevant clinical trials (CTs).

12.
Infection ; 2022.
Article in English | PubMed | ID: covidwho-1797458

ABSTRACT

PURPOSE: To assess and compare the relative efficacy and safety of anti-SARS-CoV-2 antibody regimens for COVID-19. METHODS: This systematic review and random-effects network meta-analysis was conducted according to PRISMA-NMA. Literature searches were conducted across MEDLINE, EMBASE, PubMed, Web of Science, CENTRAL, and CNKI up to February 20th, 2022. Interventions were ranked using P scores. RESULTS: Fifty-five RCTs (N = 45,005) were included in the review. Bamlanivimab + etesevimab (OR 0.13, 95% CI 0.02-0.77) was associated with a significant reduction in mortality compared to standard of care/placebo. Casirivimab + imdevimab reduced mortality (OR 0.67, 95% CI 0.50-0.91) in baseline seronegative patients only. Four different regimens led to a significant decrease in the incidence of hospitalization compared to standard of care/placebo with sotrovimab ranking first in terms of efficacy (OR 0.20, 95% CI 0.08-0.48). No treatment improved incidence of mechanical ventilation, duration of hospital/ICU stay, and time to viral clearance. Convalescent plasma and anti-COVID IVIg both led to a significant increase in adverse events compared to standard of care/placebo, but no treatment increased the odds of serious adverse events. CONCLUSION: Anti-SARS-CoV-2 mAbs are safe, and could be effective in improving mortality and incidence of hospitalization. Convalescent plasma and anti-COVID IVIg were not efficacious and could increase odds of adverse events. Future trials should further examine the effect of baseline seronegativity, disease severity, patient risk factors, and SARS-CoV-2 strain variation on the efficacy of these regimes. REGISTRATION: PROSPERO-CRD42021289903.

13.
Transfus Med ; 2022.
Article in English | PubMed | ID: covidwho-1794553

ABSTRACT

BACKGROUND: Convalescent plasma containing high levels of SARS-CoV-2 antibodies has been studied as a possible treatment for COVID-19. Better understanding of predictors of high antibody levels is needed for improving supply of high-quality therapeutic plasma. AIMS: We have evaluated demographic and clinical factors associated with the probability of a convalescent plasma donor having high SARS-CoV-2 IgG antibody levels. METHODS: A total of 29,585 convalescent plasma donors employed during the first and second waves of the COVID-19 pandemic in England were included in this study. All had been tested for SARS-CoV-2 IgG antibodies by EUROimmun ELISA. A multivariable logistic regression model was used to quantify the association of the demographic and clinical factors with high (EUROimmun S/Co>6.0) SARS-CoV-2 IgG antibody level. RESULTS: Most of the donors were male (23,024;78%), with white ethnic background (24,598;83%) and had not been tested for SARS-CoV-2 (15,266;52%).Overall, less than 20% of convalescent plasma donors with confirmed or suspected SARS-CoV-2 infection harboured high SARS-CoV-2 antibody levels (n = 4,978). We found that older male donors who had been hospitalised with COVID-19 were most likely to harbour high levels of antibodies. White donors were less likely to have high SARS-CoV-2 antibody levels than donors with Asian orblack ethnic backgrounds residing in affluent areas likely reflecting ethnic inequality previously associated with SARS-CoV-2 infection. DISCUSSION: In a time of great uncertainty, and predicted new waves associated with newly emerging SARS-CoV-2 variants, these results will help us to target future convalescent plasma collections.

14.
Microbiology Spectrum ; 10(1):13, 2022.
Article in English | Web of Science | ID: covidwho-1790201

ABSTRACT

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1354), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARSCoV-2 specific antibodies (compared to baseline) and a non-significant reduction in Ku transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.

15.
Indian Journal of Pharmaceutical Sciences ; 84:235-245, 2022.
Article in English | Scopus | ID: covidwho-1789981

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 which is the source of pandemic coronavirus disease 2019 has engulfed almost whole world. This virus was first reported in Wuhan city (China) in December 2019. Since the discovery of the virus, till today the researchers and scientists have been working to develop new vaccines or therapeutic agents against severe acute respiratory syndrome coronavirus 2. However, thus far no vaccine has emerged that can be approved to treat or prevent coronavirus disease 2019. Due to lack of specific preventative and therapeutic options for the treatment of coronavirus disease 2019, the use of convalescent plasma therapy may be of great benefit in the current situation. Previous use of immune plasma has resulted in successful treatment of hemagglutinin type 1 and neuraminidase type 1 influenza virus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 1 epidemics. In the current scenario raised by coronavirus disease 2019, the convalescent plasma therapy has been applied successfully among many patients across various regions. This article presents an up-to-date review of existing literature on recovery through convalescent plasma as a treatment of choice, safety and its efficacy, possibility and its challenges for the treatment of coronavirus disease 2019. © 2022 Indian Pharmaceutical Association. All rights reserved.

16.
Iranian Journal of War and Public Health ; 13(4):283-288, 2021.
Article in English | Scopus | ID: covidwho-1789911

ABSTRACT

Aims Coronavirus can attack the central and peripheral nervous systems in different ways and produce neurological manifestations. This study aimed to summarize the neurological manifestations and electrophysiological studies of COVID-19 patients during the recovery phase, suggesting Guillain-Barré syndrome. Patients & Methods This case report study was done in the Department of Physiology, College of Medicine at Al-Mustansiriya University, in cooperation with Al-Yarmouk Teaching Hospital in Baghdad. Patients during the convalescent period (1-3 months post-infection) of COVID-19 disease with neurological manifestations were included. Neurologists and neurosurgeons referred the patients for an electromyography and nerve conduction study to identify their illnesses. Findings Seven patients (4 females and 3 males) presented with clinical manifestations that highly suggested Guillain-Barré syndrome. The patients were presented with a rapidly progressive ascending weakness of both lower and upper limbs and diffuse, hypo-or-areflexia of the deep tendon reflexes. The sensory symptoms were distributed in both hands and feet, pain, paresthesia, and numbness. Electrophysiology studies confirmed five patients have acute inflammatory demyelinating polyradiculoneuropathy, one patient has acute motor axonal neuropathy, and one has acute motor and sensory axonal neuropathy subtypes. Conclusion Clinical manifestations of Guillain-Barré syndrome confirmed by electrophysiological studies are associated with COVID-19, which show similarity with GBS due to the post-viral infections with an autoimmune background. Therefore coronavirus infection is an etiological factor of Guillain-Barré syndrome. Copyright © 2021, the Authors ;Publishing Rights, ASPI

17.
Journal of the Indian Medical Association ; 118(7):28-33, 2020.
Article in English | Scopus | ID: covidwho-1787055

ABSTRACT

COVID 19 pandemic has a significant impact on global public health and economies. Scientists and researchers all over the world are endeavouring in search of specific drug against COVID19 virus. For a novel emerging virus, specific antiviral drug takes time before its approval for clinical use as RCTs are expensive and time consuming. In Indian perspective, many drugs which are currently under clinical trial are unavailable. Reviewing available published and unpublished papers, we intend to throw light on the drugs that can be used in the interim in India till further evidence come. Pending sufficient evidence remdesivir, favipirvair,tocilizumab,lopinavir-ritonavir with or without ribavirin;hydroxychloroquine or convalescent plasma can be considered. © 2020 Indian Medical Association. All rights reserved.

18.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-333271

ABSTRACT

We assessed the affinities of the therapeutic monoclonal antibodies (mAbs) cilgavimab, tixagevimab, sotrovimab, casirivimab, and imdevimab to the receptor binding domain (RBD) of wild type, Delta, and Omicron spike. The Omicron RBD affinities of cilgavimab, tixagevimab, casirivimab, and imdevimab decreased by at least two orders of magnitude relative to their wild type equivalents, whereas sotrovimab binding was less severely impacted. These affinity reductions correlate with reduced antiviral activities of these antibodies, suggesting that simple affinity measurements can serve as an indicator for activity before challenging and time-consuming virus neutralization assays are performed. We also compared the properties of these antibodies to serological fingerprints (affinities and concentrations) of wild type RBD specific antibodies in 74 convalescent sera. The affinities of the therapeutic mAbs to wild type and Delta RBD were in the same range as the polyclonal response in the convalescent sera indicative of their high antiviral activities against these variants. However, for Omicron RBD, only sotrovimab retained affinities that were within the range of the polyclonal response, in agreement with its high activity against Omicron. Serological fingerprints thus provide important context to affinities and antiviral activity of mAb drugs and could guide the development of new therapeutics.

19.
New Microbiol ; 45(1):62-72, 2022.
Article in English | PubMed | ID: covidwho-1782123

ABSTRACT

Convalescent plasma (CP) therapy might be effective in patients with haematological malignanciesand B-cell depletion. We report a single-centre experience of COVID-19 patients with non-Hodgkinlymphoma and absence of B-cells as a consequence of anti-CD20 therapy successfully treated withCP from October 2020 to May 2021. CP was given in the presence of pneumonia with respiratoryfailure despite standard treatment and consisted of three infusions on an alternate-day basis. A reviewof the current literature on this topic was also performed. Six patients were identified (medianage 59.5 years (range 50-73)). The last anti-CD20 drug administration occurred 60 days before infection(range 0-360). CP was administered after a median of 51 days (range 9-120) from SARS-CoV-2diagnosis, with an early improvement in all but one subject. We suggest a possible clinical benefitof convalescent CP treatment in COVID-19 patients with haematological malignancies and B-celldepletion having persistent/recurrent pneumonia.

20.
Front Mol Biosci ; 9: 797132, 2022.
Article in English | MEDLINE | ID: covidwho-1785376

ABSTRACT

The COVID-19 pandemic resulting from the spread of SARS-CoV-2 spurred devastating health and economic crises around the world. Neutralizing antibodies and licensed vaccines were developed to combat COVID-19, but progress was slow. In addition, variants of the receptor-binding domain (RBD) of the spike protein confer resistance of SARS-CoV-2 to neutralizing antibodies, nullifying the possibility of human immunity. Therefore, investigations into the RBD mutations that disrupt neutralization through convalescent antibodies are urgently required. In this study, we comprehensively and systematically investigated the binding stability of RBD variants targeting convalescent antibodies and revealed that the RBD residues F456, F490, L452, L455, and K417 are immune-escaping hotspots, and E484, F486, and N501 are destabilizing residues. Our study also explored the possible modes of actions of emerging SARS-CoV-2 variants. All results are consistent with experimental observations of attenuated antibody neutralization and clinically emerging SARS-CoV-2 variants. We identified possible immune-escaping hotspots that could further promote resistance to convalescent antibodies. The results provide valuable information for developing and designing novel monoclonal antibody drugs to combat emerging SARS-CoV-2 variants.

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