Article

Monoclonal antibody therapy in COVID-19 induced by SARS-CoV-2

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-2019 (COVID-19) which is associated with inflammation, thrombosis edema, hemorrhage, intra-alveolar fibrin deposition, and vascular and pulmonary damage. In COVID-19, the coronavirus activates macrophages by inducing the generation of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18 and TNF] that can damage endothelial cells, activate platelets and neutrophils to produce thromboxane A2 (TxA2), and mediate thrombus generation. In severe cases, all these phenomena can lead to patient death. The binding of SARS-CoV-2 to the Toll Like Receptor (TLR) results in the release of pro-IL-1β that is cleaved by caspase-1, followed by the production of active mature IL-1β which is the most important cytokine in causing fever and inflammation. Its activation in COVID-19 can cause a "cytokine storm" with serious biological and clinical consequences. Blockade of IL-1 with inhibitory and anti-inflammatory cytokines represents a new therapeutic strategy also for COVID-19. Recently, very rare allergic reactions to vaccines have been reported, with phenomena of pulmonary thrombosis. These side effects have raised substantial concern in the population. Highly allergic subjects should therefore be vaccinated under strict medical supervision. COVID-19 has accelerated vaccine therapy but also the use of drugs and monoclonal antibodies (mABs) which have been used in COVID-19 therapy. They are primarily adopted to treat high-risk mild-to-moderate non-hospitalized patients, and it has been noted that the administration of two mABs gave better results. mABs, other than polyclonal plasma antibodies from infected subjects with SARS-CoV-2, are produced in the laboratory and are intended to fight SARS-CoV-2. They bind specifically to the antigenic determinant of the spike protein, inhibiting the pathogenicity of the virus. The most suitable individuals for mAB therapy are people at particular risk, such as the elderly and those with serious chronic diseases including diabetics, hypertension and obesity, including subjects suffering from cardiovascular diseases. These antibodies have a well-predetermined target, they bind mainly to the protein S (formed by the S1A, B, C and D subtypes), located on the viral surface, and to the S2 protein that acts as a fuser between the virus and the cell membrane. Since mABs are derived from a single splenic immune cell, they are identical and form a cell clone which can neutralize SARS-CoV-2 by binding to the epitope of the virus. However, this COVID-19 therapy may cause several side effects such as mild pain, bleeding, bruising of the skin, soreness, swelling, thrombotic-type episodes, arterial hypertension, changes in heart activity, slowed bone marrow activity, impaired renal function, diarrhea, fatigue, nausea, vomiting, allergic reaction, fever, and possible subsequent infection may occur at the site of injection. In conclusion, the studies promoting mAB therapy in COVID-19 are very promising but the results are not yet definitive and more investigations are needed to certify both their good neutralizing effects of SARS-CoV-2, and to eliminate, or at least mitigate, the harmful side effects.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... As noted earlier, obesity may also be associated with increased risk of COVID-19 infection and complications due to its role in mediating a pro-inflammatory state, which can lead to sub-optimal immune responses via immune system dysregulation [7]. An array of inflammatory cytokines are increased in obese tissues, such as tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), interleukin (IL)-6, IL-1β, CCL2, and Toll-like receptors (TLRs) of the innate immune system, which may have additional implications in responses to vaccination and viral infections [105,106]. The activation of IL-1β and IL-6 in COVID-19 has been associated with "cytokine storms", which can have severe biological and clinical consequences [106]. ...
... An array of inflammatory cytokines are increased in obese tissues, such as tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), interleukin (IL)-6, IL-1β, CCL2, and Toll-like receptors (TLRs) of the innate immune system, which may have additional implications in responses to vaccination and viral infections [105,106]. The activation of IL-1β and IL-6 in COVID-19 has been associated with "cytokine storms", which can have severe biological and clinical consequences [106]. ...
... Educational efforts addressing poor dietary intake, overweight and obesity, and now also vaccination to reduce the risk of COVID-19 infections and its complications have met resistance related to intense counter-messaging that influences behavioral choices and that are not in an individual's best interest. Ongoing community-level efforts addressing both overweight and obesity and COVID-19 need to be pursued and reinforced while ensuring that respectful yet accurate messaging reaches the communities in greatest need [20, 105,106]. ...
Article
Full-text available
Food insecurity in the United States has been exacerbated due to the socioeconomic strain of the coronavirus disease 2019 (COVID-19) pandemic. Populations experiencing poverty and, as a consequence, food insecurity in the United States are disproportionately affected by obesity, which was identified early in the pandemic as a major risk factor for increased susceptibility to COVID-19 infection and mortality. Given the focus on obesity and its role in immune dysregulation, it is also important to note the role of micronutrient deficiency, another sequalae of food insecurity. Micronutrients play an important role in the ability of the immune system to mount an appropriate response. Moreover, OBESE individuals are more likely to be micronutrient deficient. This review will explore the role of micronutrients, vitamin A, vitamin D, vitamin C, and zinc in respiratory immunity and COVID-19 and how micronutrient deficiency may be a possible confounder in obesity’s association with severe outcomes. By illuminating the role of micronutrients in COVID-19, this paper expands the discussion from food insecurity and obesity to include micronutrient deficiency and how all of these interact in respiratory illnesses such as COVID-19.
... mAbs are produced from pathogen-specific B cells found in humans who recovered following infection and also from animals like mice (by immunizing them to have a genetically modified humanized immune system). 8 After identification of B cells, the genes of heavy and light chain components are studied and these genes are expressed to produce mAbs that have a specific target. 8 The different proteins of SARS-CoV-2 genome can be grouped into structured, unstructured and accessory proteins. ...
... 8 After identification of B cells, the genes of heavy and light chain components are studied and these genes are expressed to produce mAbs that have a specific target. 8 The different proteins of SARS-CoV-2 genome can be grouped into structured, unstructured and accessory proteins. The four major proteins of structured proteins are used as targets for developing mAbs and these are spike (S), envelope (E), membrane (M) and nucleocapsid (N). ...
... This mAb binds to the receptor-binding domain of the spike protein of SARS-CoV-2 and thereby preventing the attachment of spike protein to ACE2. 8,11 Bamlanivimab was approved as a monotherapy on November 2020 based on the interim analysis of RCT on mild to moderate COVID -19 infected patients who were at high risk of progression to severe disease. 8 But due to concern for a sustained increase in variants of SARS-CoV-2 which shows resistance to Bamlanivimab monotherapy on March 24, 2021, the U.S. department of health and human services issued a notice to stop the distribution of Bamlanivimab as monotherapy. ...
Article
Full-text available
Coronavirus disease 2019 (COVID-19) was declared as pandemic on March 11th 2020 by the world health organization (WHO). Vaccination is for preventing COVID-19 morbidity but when people are infected, treatment is required and even after one and half years the effective cure is yet to be discovered. In this context monoclonal antibodies (mAbs) are promising innovative therapeutic agents in controlling COVID-19 infection. Researchers have found more than 50 mAbs against COVID-19 and they are at different stages of development. Scientists are pacing the research on mAbs. mAbs are innovative therapeutic agents in this context a scoping narrative review was done. At present we have evidences from numerous randomized controlled trials (RCT) on mAbs in effective control of respiratory and coagulation related complications due to COVID-19 infection. Many have got emergency use approval and few of which were withdrawn due to absence of enough evidences or adverse reactions. Examples are bamlanivimab, etesevimab, casirivimab and imdevimab. Other than these many investigational (mAbs) are under scrutiny. With the current evidences the article will give an insight to new and repurposed mAbs which are still under investigation in the management of COVID-19 infections.
... mAbs are produced from pathogen-specific B cells found in humans who recovered following infection and also from animals like mice (by immunizing them to have a genetically modified humanized immune system). 8 After identification of B cells, the genes of heavy and light chain components are studied and these genes are expressed to produce mAbs that have a specific target. 8 The different proteins of SARS-CoV-2 genome can be grouped into structured, unstructured and accessory proteins. ...
... 8 After identification of B cells, the genes of heavy and light chain components are studied and these genes are expressed to produce mAbs that have a specific target. 8 The different proteins of SARS-CoV-2 genome can be grouped into structured, unstructured and accessory proteins. The four major proteins of structured proteins are used as targets for developing mAbs and these are spike (S), envelope (E), membrane (M) and nucleocapsid (N). ...
... This mAb binds to the receptor-binding domain of the spike protein of SARS-CoV-2 and thereby preventing the attachment of spike protein to ACE2. 8,11 Bamlanivimab was approved as a monotherapy on November 2020 based on the interim analysis of RCT on mild to moderate COVID -19 infected patients who were at high risk of progression to severe disease. 8 But due to concern for a sustained increase in variants of SARS-CoV-2 which shows resistance to Bamlanivimab monotherapy on March 24, 2021, the U.S. department of health and human services issued a notice to stop the distribution of Bamlanivimab as monotherapy. ...
Article
Full-text available
Coronavirus disease 2019 (COVID-19) was declared as pandemic on March 11th 2020 by the world health organization (WHO). Vaccination is for preventing COVID-19 morbidity but when people are infected, treatment is required and even after one and half years the effective cure is yet to be discovered. In this context monoclonal antibodies (mAbs) are promising innovative therapeutic agents in controlling COVID-19 infection. Researchers have found more than 50 mAbs against COVID-19 and they are at different stages of development. Scientists are pacing the research on mAbs. mAbs are innovative therapeutic agents in this context a scoping narrative review was done. At present we have evidences from numerous randomized controlled trials (RCT) on mAbs in effective control of respiratory and coagulation related complications due to COVID-19 infection. Many have got emergency use approval and few of which were withdrawn due to absence of enough evidences or adverse reactions. Examples are bamlanivimab, etesevimab, casirivimab and imdevimab. Other than these many investigational (mAbs) are under scrutiny. With the current evidences the article will give an insight to new and repurposed mAbs which are still under investigation in the management of COVID-19 infections.
... Os anticorpos monoclonais (mAbs) correspondem aqueles que são produzidos por um único clone de um linfócito B, sendo cada tipo de mAb responsável por ligar-se a uma determinada substância no corpo (JAHANSHAHLU; REZAEI, 2020). Os efeitos adversos incluem dor, episódios trombóticos, hipertensão arterial, alterações na atividade cardíaca, constipação, declínio na função renal, diarreia, fadiga, náuseas, vômitos, febre, entre outros (CONTI et al., 2021). Além disso, foram relatados casos de piora da função respiratória devido ao acúmulo de inflamação pulmonar (JAHANSHAHLU; REZAEI, 2020). ...
... Desta forma, ocorrerá aumento da liberação de citocinas pró-inflamatórias por estas células, induzindo a tempestade de citocinas e, consequentemente, efeitos adversos fatais para os pacientes (CONTI et al., 2021). ...
Article
Em dezembro de 2019, a cidade de Wuhan, na China, foi palco do aparecimento de uma nova doença infecciosa, denominada Doença do Coronavírus 2019 (COVID-19), a qual em poucos meses se espalhou pelos continentes, originando uma pandemia, com elevado número de casos e mais de 6 milhões de mortes até setembro de 2022. A COVID-19 é causada pelo Coronavírus 2 da Síndrome Respiratória Aguda Grave (SARS-CoV-2), sendo muito mais transmissível e patogênico que os antigos coronavírus, visto que sua infecção pode levar ao risco de internações em UTIs, necessidade de suporte ventilatório, alto número de óbitos e sequelas. Frente a esse cenário, iniciou-se uma busca a nível mundial por tratamentos que alterassem o prognóstico da doença grave, em que diversos medicamentos foram citados e alguns foram aprovados para uso emergencial, mesmo sem pesquisas e resultados adequados para comprovar sua eficácia. Deste modo, o presente trabalho objetivou realizar uma revisão integrativa de literatura sobre as evidências científicas voltadas ao tratamento farmacológico da forma grave da doença. Ademais, foram descritos os benefícios, efeitos adversos e indicação de algumas das medicações mais utilizadas até o momento, sendo estas os Glicocorticoides, Remdesivir, Anticorpos Monoclonais, como o Tocilizumabe, Anakinra, Inibidores da JAK (Baricitinibe). Entretanto, baseado na seleção bibliográfica desta revisão, nenhum dos medicamentos avaliados obteve resultados irrefutáveis sobre seu uso no tratamento da COVID-19, sendo imprescindível balancear os possíveis riscos e benefícios da utilização de cada um deles.
... This positive profile in AECA autoantibodies raises intriguing questions about the interplay between SARS-CoV-2 infection and the immune response. Activation of macrophages by coronavirus, inducing the generation of pro-inflammatory cytokines (interleukin (IL)-1, IL-6, IL-18, and TNF) that can damage endothelial cells and activate platelets and neutrophils, has been reported in several studies [39]. Specifically, cytokine storms, result from the dysregulation of endothelial cells, characterized by abnormal coagulation and vascular leakage [40]. ...
Article
Full-text available
Background: Olfactory impairment, particularly hyposmia and anosmia, has emerged as a distinctive early symptom of SARS-CoV-2. Drawing on the historical association of autoimmune diseases with olfactory function, this study delves into the connections between COVID-19, autoimmunity, and persistent olfactory dysfunctions, focusing on individuals experiencing long-lasting smell disorders (3-18 months post-SARS-CoV-2 infection). Methods: The study comprised 36 Long Covid patients with persistent olfactory dysfunctions, alongside two control groups. Olfactory functionality was assessed using the Sniffin' Sticks extended test. Non-invasive olfac-tory mucosa brushing and nasal secretions were processed for nasal samples, while serum samples were obtained through peripheral venous sampling. A panel of autoantibodies, including Immunocirculating Complexes, ANA, ENA, and AECA, was investigated in serum and brush supernatant samples. Results: Contrary to expectations, the absence of traditional autoantibodies challenges the proposed autoimmune etiology of Long Covid-associated olfactory dysfunction. However, the presence and potential pathogenic role of AECA suggest viral cytopathic and inflammatory involvement in specific anatomical districts. One hypothesis explores the impact of inflammation and cytokine release induced by the viral infection, altering neuronal signaling and contributing to persistent hyposmia. Conclusion: This research contributes to our understanding of the complex relationships between autoimmunity, olfactory impairment, and COVID-19. The absence of classical autoantibodies challenges prevailing theories, while the prominence of AECA hints at unique viral-induced pathogenic mechanisms. By unraveling these complexities, this study enhances our comprehension of post-acute sequelae, offering valuable perspectives on immune-mediated responses in the aftermath of the pandemic.
... mAbs have some serious advantages, for example, high specificity that is helpful for exact action, and long halflives that is useful for rare dosing. [8] Other uncommon adverse events caused mAbs used are: vomiting, abdominal pain, fatigue, dysphonia, anorexia, peripheral neuropathy and leukoencephalopathy. [9][10][11][12][13][14] The Cytokine Storm [15,16] Several mAbs start the discharge of several cytokines, which may cause a cytokine storm. [17,18] This is valid for muromonab, [19] alemtuzumab, [20,21] and rituximab. ...
... However, limited clinical benefit of using mABs, several side effects by using vaccines, and obstacles in the treatment of Long Covid-19 syndrome necessitates the development of efficient clinical methods that may effectively prevent viral entry and IL-1 blockade at the first place. 11,12 Meanwhile, maintaining health recommendations such as wearing a well-fitting mask, washing hands regularly, constant ventilation of indoor spaces, keeping social distancing, testing frequently, and vaccinating along with booster doses still remained essential. On the other hand, global communities should take Omicron even more seriously than before. ...
Article
Full-text available
Introduction: In November 26th, 2021 a new strain of SARS-CoV-2 was designated by the World Health Organization as a variant of concern and named Omicron. The news broadcasted a global wave of panic and anxiety while many, like 2 years ago, were making themselves ready for the holiday season. After almost a month of its designation, countries from all 6 continents have been reported Omicron from their genomic sequences. This triggered an international alarm about a new era in the Covid-19 pandemic, where despite the vast amount of vaccinations, a surge in new cases and hospitalizations are reported from all over the world. Methods: Scientific literature published from November 26, 2021 to March 21, 2022 have been searched and retrieved by using "SARS-COV-2", "Omicron", "B.1.1.529", "Covid-19", and "global community" keywords from "PubMed", "Web o "Google Scholar", and "MedRxiv" databases. Results: Omicron have been evolved to spread faster than previous variants of concern, but it infects people lesser than other variants, Delta for example. Omicron can also escape vaccine-induced immunity more than previous SARS-CoV-2 variants. Discussion: Despite possible lower lethal risks than previous strains, Omicron may provide populations with a higher community transmission and a higher hospitalization load, which potentially overwhelm already exhausted health care systems. Therefore, we need to get used to the "New Normal" and maintain health recommendations to help decrease spreading of the virus and buy more time for the scientists to dive deeper into potential ways of tackling Covid-19, more than ever.
... After that, glucocorticoids should be justified based on two diverse pathophysiological phases of the SAR-CoV-2 infection: (1) in the initial stage, administration of pharmacological doses of CS might essentially upsurge the plasma viral load because of immunosuppression, and (2) in the late phase (hyperinflammatory COVID-CS stage), CS pharmacodynamic properties will suppress hyperinflammation and alleviate the COVID-19-induced cytokine storm [308]. Furthermore, adrenal cortical steroid, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, monoclonal antibodies, low molecular weight heparin, and antimalarial agents have been reported as potentially beneficial and dependable therapeutic options for the management of COVID-CS [297,[309][310][311][312][313][314][315][316][317][318][319][320]. Plausibly, these therapeutic options possibly will work and safeguard COVID-CS patients. ...
Article
Full-text available
A significant part of the world population has been affected by the devastating SARS-CoV-2 infection. It has deleterious effects on mental and physical health and global economic conditions. Evidence suggests that the pathogenesis of SARS-CoV-2 infection may result in immunopathology such as neutrophilia, lymphopenia, decreased response of type I interferon, monocyte, and macrophage dysregulation. Even though most individuals infected with the SARS-CoV-2 virus suffer mild symptoms similar to flu, severe illness develops in some cases, including dysfunction of multiple organs. Excessive production of different inflammatory cytokines leads to a cytokine storm in COVID-19 infection. The large quantities of inflammatory cytokines trigger several inflammation pathways through tissue cell and immune cell receptors. Such mechanisms eventually lead to complications such as acute respiratory distress syndrome, intravascular coagulation, capillary leak syndrome, failure of multiple organs, and, in severe cases, death. Thus, to devise an effective management plan for SARS-CoV-2 infection, it is necessary to comprehend the start and pathways of signaling for the SARS-CoV-2 infection-induced cytokine storm. This article discusses the current findings of SARS-CoV-2 related to immunopathology, the different paths of signaling and other cytokines that result in a cytokine storm, and biomarkers that can act as early signs of warning for severe illness. A detailed understanding of the cytokine storm may aid in the development of effective means for controlling the disease’s immunopathology. In addition, noting the biomarkers and pathophysiology of severe SARS-CoV-2 infection as early warning signs can help prevent severe complications
... After that, glucocorticoids should be justified based on two diverse pathophysiological phases of the SAR-CoV-2 infection: (1) in the initial stage, administration of pharmacological doses of CS might essentially upsurge the plasma viral load because of immunosuppression, and (2) in the late phase (hyperinflammatory COVID-CS stage), CS pharmacodynamic properties will suppress hyperinflammation and alleviate the COVID-19-induced cytokine storm [308]. Furthermore, adrenal cortical steroid, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, monoclonal antibodies, low molecular weight heparin, and antimalarial agents have been reported as potentially beneficial and dependable therapeutic options for the management of COVID-CS [297,[309][310][311][312][313][314][315][316][317][318][319][320]. Plausibly, these therapeutic options possibly will work and safeguard COVID-CS patients. ...
Article
Full-text available
A significant part of the world population has been affected by the devastating SARS-CoV-2 infection. It has deleterious effects on mental and physical health and global economic conditions. Evidence suggests that the pathogenesis of SARS-CoV-2 infection may result in immunopathology such as neutrophilia, lymphopenia, decreased response of type I interferon, monocyte, and macrophage dysregulation. Even though most individuals infected with the SARS-CoV-2 virus suffer mild symptoms similar to flu, severe illness develops in some cases, including dysfunction of multiple organs. Excessive production of different inflammatory cytokines leads to a cytokine storm in COVID-19 infection. The large quantities of inflammatory cytokines trigger several inflammation pathways through tissue cell and immune cell receptors. Such mechanisms eventually lead to complications such as acute respiratory distress syndrome, intravascular coagulation, capillary leak syndrome, failure of multiple organs, and, in severe cases, death. Thus, to devise an effective management plan for SARS-CoV-2 infection, it is necessary to comprehend the start and pathways of signaling for the SARS-CoV-2 infection-induced cytokine storm. This article discusses the current findings of SARS-CoV-2 related to immunopathology, the different paths of signaling and other cytokines that result in a cytokine storm, and biomarkers that can act as early signs of warning for severe illness. A detailed understanding of the cytokine storm may aid in the development of effective means for controlling the disease’s immunopathology. In addition, noting the biomarkers and pathophysiology of severe SARS-CoV-2 infection as early warning signs can help prevent severe complications.
... More recently, the US Food and Drug Administration issued an emergency use authorization for the use of tocilizumab in certain populations of patients with COVID-19 [6] and the European Medicines Agency [7] recommended that tocilizumab be indicated for the treatment of selected adults with COVID-19 after promising clinical trial results [8]. COVID-19 induces the generation of proinflammatory cytokines including IL-6 leading to host cell damage [9]. Tocilizumab is available as both an intravenous and subcutaneous formulation, the latter of which might be more convenient for patients because it allows once-weekly self-administration [10]. ...
Article
Full-text available
Background: Tocilizumab is a recombinant humanized monoclonal immunoglobulin G1 antibody against the interleukin-6 receptor (IL-6R). MSB11456 is a proposed tocilizumab biosimilar. Objectives: To assess the pharmacokinetic and pharmacodynamic similarity of MSB11456 to both US-licensed and EU-approved tocilizumab. Methods: Healthy adult volunteers (N=685) received a single 162 mg subcutaneous injection of MSB11456, US-licensed tocilizumab, or EU-approved tocilizumab in this randomized, double-blind, parallel-group study. Blood samples were taken predose and for up to 48 days postdose. Primary endpoint pharmacokinetic parameters were analyzed using analysis of covariance. Secondary pharmacodynamic measures included serum-soluble IL-6R and serum C-reactive protein. Safety data were analyzed descriptively. Results: Pharmacokinetic equivalence (with all corresponding 90% confidence intervals for the geometric least squares mean ratios within the predefined 80.00% to 125.00% equivalence margin) was demonstrated between MSB11456 and both US-licensed and EU-approved tocilizumab, as well as between the reference products. Pharmacodynamic analyses demonstrated similarity of MSB11456 and both US-licensed and EU-approved tocilizumab, as well as between the reference products. Safety, tolerability and immunogenicity were comparable between treatments. Conclusion: : Pharmacokinetic and pharmacodynamic similarity of MSB11456, US-licensed tocilizumab, and EU-approved tocilizumab were demonstrated, and the three products had comparable immunogenicity and safety, supporting MSB11456 as a biosimilar to tocilizumab.
... Infection with SARS-CoV-2 leads to COVID-19, the severity of which is partly due to host immune responses, including the release of proinflammatory cytokines, such as interleukin (IL)-6, IL-18 and tumor necrosis factor (TNF), with serious biological and clinical consequences [21,22]. Vaccination is considered one of the most effective strategies to fight against infectious diseases. ...
Article
Full-text available
The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.
... Generally, the data show inhibition of the pathogenicity of the virus on the one hand and draw attention to several side effects that can appear during treatment on the other hand. Therefore, the need for further research to certify the SARS-CoV-2 neutralization effects and limit/mitigate the adverse events associated with this kind of therapy is emphasized [60]. As for IFN, Darazam et al. [61] evaluated the safety and efficacy of two most promising type I interferons, i.e., interferon beta-1a (IFNβ-1a) and interferon beta-1b (IFNβ-1b), on the course and outcomes of severe COVID-19 patients. ...
Article
Full-text available
The current report provides a brief overview of the clinical features, hematological/biochemical abnormalities, biomarkers, and AI-related strategies in COVID-19; presents in a nutshell the pharmacological and non-pharmacological therapeutic options; and concisely summarizes the most important aspects related to sociodemographic and behavioral factors as well as comorbidities having an impact on this disease. It also gives a brief outline of the effect of selected elements on immune response and collects data on the levels of micro-/macro-elements and toxic metals in the blood/urine of SARS-CoV-2 infected patients and on supplementation with minerals in COVID-19 subjects. Moreover, this review provides an overview of clinical trials based on the use of minerals alone or in combination with other agents that can provide effective responses toward SARS-CoV-2 infection. The knowledge compiled in this report lays the groundwork for new therapeutic treatments and further research on biomarkers that should be as informative as possible about the patient’s condition and can provide more reliable information on COVID-19 course and prognosis. The collected results point to the need for clarification of the importance of mineral supplementation in COVID-19 and the relationships of the levels of some minerals with clinical improvement.
... The antigen introduced into the body by injection, insect bite or absorption by the intestinal mucosa, activates MCs simultaneously in many tissues which first release inflammatory chemical mediators and then pro-inflammatory cytokines, with serious damage to the organism that can even lead to death. The release of the mediators of inflammation causes plasma loss, a drop in blood pressure and anaphylactic shock which can be anti-COVID-19 vaccines has caused a small number of allergic reactions, causing apprehension in the world population (9). Vaccines can provoke, albeit in very few instances, severe acute systemic IgE or IgG-mediated and anaphylactic reactions with complement participation. ...
Article
Anaphylaxis is a severe multisystem reaction that occurs rapidly after the introduction of an antigen that would otherwise be a harmless substance. It is characterized by airway and respiratory problems, cardiovascular collapse, mucosal inflammation, and other complications, all severe symptoms that can cause death. IgE-dependent anaphylaxis involves mast cells (MCs) which are the main sources of biologically active mediators that contribute to the pathological and lethal phenomena that can occur in anaphylaxis. Antibody-mediated anaphylaxis can follow multiple pathways such as that mediated by MCs carrying the FcεRI receptor, which can be activated by very small amounts of antigen including a vaccine antigen and trigger an anaphylactic reaction. In addition, anaphylaxis can also be provoked by high concentrations of IgG antibodies that bind to the FcγR receptor present on basophils, neutrophils, macrophages and MCs. For this reason, the IgG concentration should be kept under control in vaccinations. Activation of MCs is a major cause of anaphylaxis, which requires immediate treatment with epinephrine to arrest severe lethal symptoms. MCs are activated through the antigen binding and cross-linking of IgE with release of mediators such as histamine, proteases, prostaglandins, leukotrienes and inflammatory cytokines. The release of these compounds causes nausea, vomiting, hives, wheezing, flushing, tachycardia, hypotension, laryngeal edema, and cardiovascular collapse. mRNA and viral vector vaccines have been cleared by the United States, Food and Drug Administration (FDA), generating hope of prevention and cure for COVID-19 around the world. Scientists advise against giving the vaccine to individuals who have had a previous history of anaphylaxis. The US Centers for Disease Control and Prevention (CDC) advises people with a previous history of any immediate allergic reaction to remain under observation for approximately 30 minutes after COVID-19 vaccination. To date, vaccines that prevent SARS-CoV-2 infection have not raised major concerns of severe allergic reactions, although, in some cases, pain and redness at the injection site and fever have occurred after administration of the vaccine. These reactions occur in the first 24-48 hours after vaccination. It has been reported that probable forms of anaphylaxis could also occur, especially in women approximately 40 years of age. But after tens of millions of vaccinations, only a few patients had this severe reaction with a low incidence. Anaphylactic and severe allergic reactions can also occur to any component of the vaccine including polysorbates and polyethylene glycol. To date, there is no precise information on allergic reactions to COVID-19 vaccines. Individuals with MCs and complement with higher activation than others may be at greater allergic risk. Moreover, the reactions called anaphylactoids, are those not mediated by IgE because they do not involve this antibody and can also occur in COVID-19 vaccination. These not-IgE-mediated reactions occur through direct activation of MCs and complement with tryptase production, but to a lesser extent than IgE-mediated anaphylaxis. However, at the moment it is not known exactly which component of the vaccine causes the allergic reaction and which vaccine causes the most side effects, including anaphylaxis. Thus, individuals who have a known allergy to any component of the vaccine should not be vaccinated. However, should an anaphylactic reaction occur, this requires immediate treatment with epinephrine to arrest severe lethal symptoms. In conclusion, the purpose of this editorial is to encourage the population to be vaccinated in order to extinguish this global pandemic that is afflicting the world population, and to reassure individuals that anaphylactic reactions do not occur with a higher incidence than other vaccinations.
Chapter
Monoclonal antibodies (mAbs) are important theranostic tools in the clinics due to their affinity to bind with specific antigen. Since their development, mAbs have been impacted in clinical interventions enormously and are considered as more precise than other treatments. However, murine-based mAbs have shown immunogenic reactions, leading to reduced efficacy. The development of chimeric and humanized mAbs reduced the immunogenic response with improved efficacy. In addition, antibodies produced using phage display systems, genetically engineered animals and plants have added advantage for the use of mAbs in organ transplant and targeted therapy in several diseases including cancer. However, mutations in the target genes, their expression level, and undesirous infusion reactions are the major limitations of mAb-based therapeutics. The more significant but less common risks associated with unwanted immunogenic reactions, including acute anaphylaxis, cytokine release syndrome, and serum sickness, are the major areas for future investigations.
Article
Full-text available
Introduction: The acute respiratory distress syndrome (ARDS), secondary to viral pneumonitis, is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019)—ongoing SARS-CoV-2 infection— reached more than 0.7 billion registered cases. Methods: Recently, we elaborated a non-surgical and reproducible method of the unilateral total diffuse alveolar damage (DAD) of the left lung in ICR mice–a publicly available imitation of the ARDS caused by SARS-CoV-2. Our data read that two C–C chemokine receptor 5 (CCR5) ligands, macrophage inflammatory proteins (MIPs) MIP-1α/CCL3 and MIP-1β/CCL4, are upregulated in this DAD model up to three orders of magnitude compared to the background level. Results: Here, we showed that a nonpeptide compound TAK-779, an antagonist of CCR5/CXCR3, readily prevents DAD in the lung with a single injection of 2.5 mg/kg. Histological analysis revealed reduced peribronchial and perivascular mononuclear infiltration in the lung and mononuclear infiltration of the wall and lumen of the alveoli in the TAK-779-treated animals. Administration of TAK-779 decreased the 3–5-fold level of serum cytokines and chemokines in animals with DAD, including CCR5 ligands MIP-1α/β, MCP-1, and CCL5. Computed tomography revealed rapid recovery of the density and volume of the affected lung in TAK-779-treated animals. Discussion: Our pre-clinical data suggest that TAK-779 is more effective than the administration of dexamethasone or the anti-IL6R therapeutic antibody tocilizumab, which brings novel therapeutic modality to TAK-779 and other CCR5 inhibitors for the treatment of virus-induced hyperinflammation syndromes, including COVID-19.
Article
Full-text available
One of the most pressing challenges associated with SARS-CoV-2 treatment is the emergence of new variants that may be more transmissible, cause more severe disease, or be resistant to current treatments and vaccines. The emergence of SARS-CoV-2 has led to a global pandemic, resulting in millions of deaths worldwide. Various strategies have been employed to combat the virus, including neutralizing monoclonal antibodies (mAbs), CRISPR/Cas13, and antisense oligonucleotides (ASOs). While vaccines and small molecules have proven to be an effective means of preventing severe COVID-19 and reducing transmission rates, the emergence of new virus variants poses a challenge to their effectiveness. Monoclonal antibodies have shown promise in treating early-stage COVID-19, but their effectiveness is limited in severe cases and the emergence of new variants may reduce their binding affinity. CRISPR/Cas13 has shown potential in targeting essential viral genes, but its efficiency, specificity, and delivery to the site of infection are major limitations. ASOs have also been shown to be effective in targeting viral RNA, but they face similar challenges to CRISPR/Cas13 in terms of delivery and potential off-target effects. In conclusion, a combination of these strategies may provide a more effective means of combating SARS-CoV-2, and future research should focus on improving their efficiency, specificity, and delivery to the site of infection. It is evident that the continued research and development of these alternative therapies will be essential in the ongoing fight against SARS-CoV-2 and its potential future variants.
Article
Full-text available
The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 responsible for the global COVID-19 pandemic has caused almost 760 million confirmed cases and 7 million deaths worldwide, as of end-February 2023. Since the beginning of the first COVID-19 case, several virus variants have emerged: Alpha (B1.1.7), Beta (B135.1), Gamma (P.1), Delta (B.1.617.2) and then Omicron (B.1.1.529) and its sublineages. All variants have diversified in transmissibility, virulence, and pathogenicity. All the newly emerging SARS-CoV-2 variants appear to contain some similar mutations associated with greater "evasiveness" of the virus to immune defences. From early 2022 onward, several Omicron subvariants named BA.1, BA.2, BA.3, BA.4, and BA.5, with comparable mutation forms, have followed. After the wave of contagions caused by Omicron BA.5, a new Indian variant named Centaurus BA.2.75 and its new subvariant BA.2.75.2, a second-generation evolution of the Omicron variant BA.2, have recently been identified. From early evidence, it appears that this new variant has higher affinity for the cell entry receptor ACE-2, making it potentially able to spread very fast. According to the latest studies, the BA.2.75.2 variant may be able to evade more antibodies in the bloodstream generated by vaccination or previous infection, and it may be more resistant to antiviral and monoclonal antibody drug treatments. In this manuscript, the authors highlight and describe the latest evidences and critical issues have emerged on the new SARS-CoV-2 variants.
Article
Full-text available
Acute respiratory distress syndrome (ARDS) is characterized by increased permeability of the alveolar-capillary membrane, a thin barrier composed of adjacent monolayers of alveolar epithelial and lung microvascular endothelial cells. This results in pulmonary edema and severe hypoxemia and is a common cause of death after both viral (e.g., SARS-CoV-2) and bacterial pneumonia. The involvement of the lung in ARDS is notoriously heterogeneous, with consolidated and edematous lung abutting aerated, less injured regions. This makes treatment difficult, as most therapeutic approaches preferentially affect the normal lung regions or are distributed indiscriminately to other organs. In this review, we describe the use of thoracic ultrasound and microbubbles (USMB) to deliver therapeutic cargo (drugs, genes) preferentially to severely injured areas of the lung and in particular to the lung endothelium. While USMB has been explored in other organs, it has been under-appreciated in the treatment of lung injury since ultrasound energy is scattered by air. However , this limitation can be harnessed to direct therapy specifically to severely injured lungs. We explore the cellular mechanisms governing USMB and describe various permutations of cargo administration. Lastly, we discuss both the challenges and potential opportunities presented by USMB in the lung as a tool for both therapy and research.
Article
Full-text available
Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical safety risks related to ADE, resulting in failed vaccine trials. Here, we describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. We also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2.
Article
Full-text available
IL-1 induces a significant number of metabolic and hematological changes. In experimental animals, IL-1 treatments cause hypotension due to rapid reduction of systemic blood pressure, reduced vascular resistance, increased heart rate and leukocyte aggregations. IL-1 causes endothelial dysfunction, the triggering factor of which may be of a different nature including pathogen infection. This dysfunction, which includes macrophage intervention and increased protein permeability, can be mediated by several factors including cytokines and arachidonic acid products. These effects are caused by the induction of IL-1 in various pathologies, including those caused by pathogenic viral infections, including SARS-CoV-2 which provokes COVID-19. Activation of macrophages by coronavirus-19 leads to the release of pro-inflammatory cytokines, metalloproteinases and other proteolytic enzymes that can cause thrombi formation and severe respiratory dysfunction. Patients with COVID-19, seriously ill and hospitalized in intensive care, present systemic inflammation, intravascular coagulopathy with high risk of thrombotic complications, and venous thromboembolism, effects mostly mediated by IL-1. In these patients the lungs are the most critical target organ as it can present an increase in the degradation products of fibrin, fibrinogen and D-dimer, with organ lesions and respiratory failure. It is well known that IL-1 induces itself and another very important pro-inflammatory cytokine, TNF, which also participates in hemodynamic states, including shock syndrome in COVID-19. Both IL-1 and TNF cause pulmonary edema, thrombosis and bleeding. In addition to hypotension and resistance of systemic blood pressure, IL-1 causes leukopenia and thrombocytopenia. The formation of thrombi is the main complication of the circulatory system and functionality of the organ, and represents an important cause of morbidity and mortality. IL-1 causes platelet vascular thrombogenicity also on non-endothelial cells by stimulating the formation of thromboxane A2 which is released into the inflamed environment. IL-1 is the most important immune molecule in inducing fever, since it is involved in the metabolism of arachidonic acid which increases from vascular endothelial organs of the hypothalamus. The pathogenesis of thrombosis, vascular inflammation and angigenesis involves the mediation of the activation of the prostanoid thromboxane A2 receptor. In 1986, in an interesting article (Conti P, Reale M, Fiore S, Cancelli A, Angeletti PU, Dinarello CA. In vitro enhanced thromboxane B2 release by polymorphonuclear leukocytes and macrophages after treatment with human recombinant interleukin 1. Prostaglandins. 1986 Jul;32(1):111-5), we reported for the first time that IL-1 induces thromboxane B2 (TxB2) releases in activated neutrophils and macrophages. An increase in thromboxane can induce leukocyte aggregation and systemic inflammation, which would account for the dramatic thrombi formation and organ dysfunction. Hence, IL-1 stimulates endothelial cell-leukocyte adhesion, and TxB2 production. All these events are supported by the large increase in neutrophils that adhere to the lung and the decrease in lymphocytes. Therefore, ecosanoids such as TxA2 (detected as TxB2) have a powerful action on vascular inflammation and platelet aggregation, mediating the formation of thrombi. The thrombogenesis that occurs in COVID-19 includes platelet and cell aggregation with clotting abnormalities, and anti-clotting inhibitor agents are used in the prevention and therapy of thrombotic diseases. Prevention of or induction of TxA2 avoids thrombi formation induced by IL-1. However, in some serious vascular events where TxA2 increases significantly, it is difficult to inhibit, therefore, it would be much better to prevent its induction and generation by blocking its inductors including IL-1. The inhibition or lack of formation of IL-1 avoids all the above pathological events which can lead to death of the patient. The treatment of innate immune cells producing IL-1 with IL-1 receptor antagonist (IL-1Ra) can avoid hemodynamic changes, septic shock and organ inflammation by carrying out a new therapeutic efficacy on COVID-19 induced by SARS-CoV-2.
Article
Full-text available
The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19. Vaccines and targeted therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently lacking. Here, the authors report a human monoclonal antibody capable of neutralizing both authentic SARS-CoV and SARS-CoV-2 by targeting a common epitope.
Article
Full-text available
Hypertension is recognized as an important risk factor for cardiovascular morbidity and mortality. Lowering of blood pressure has been shown to minimize the risk of cardiovascular events, with the majority of antihypertensives demonstrating a similar ability to reduce coronary events and stroke for a given reduction in blood pressure. Agents that modify the activity of the renin-angiotensin system (RAS) have been proposed to exhibit additional effects that might go beyond simple blood pressure lowering. The RAS is a crucial system that regulates extracellular fluid volume and blood pressure. Proposed potential benefits of RAS blockade that go beyond blood pressure lowering include a reduction in platelet aggregation and thrombosis, blunting of cardiac and vascular remodeling, favorable metabolic effects and reno- and cerebro-protection. However, factors such as treatment adherence, duration of action of antihypertensive agents and differences in effects on central versus brachial blood pressure may also result in apparent differences in efficacy of different antihypertensives. The aim of this review article is to examine the available data from clinical studies of antihypertensive drugs for evidence of effects that might legitimately be claimed to go beyond simple blood pressure lowering.
Article
Importance Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19. Objective To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19. Design, Setting, and Participants The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. Interventions Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156). Main Outcomes and Measures The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19–related hospitalization, an emergency department [ED] visit, or death at day 29). Results Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was –3.72 for 700 mg, –4.08 for 2800 mg, –3.49 for 7000 mg, –4.37 for combination treatment, and –3.80 for placebo. Compared with placebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, –0.35 to 0.52; P = .69) for 700 mg, –0.27 (95% CI, –0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, –0.13 to 0.76; P = .16) for 7000 mg, and –0.57 (95% CI, –1.00 to –0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group were statistically significant for 10 of 84 end points. The proportion of patients with COVID-19–related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg, 1.9% (2 events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment. Conclusions and Relevance Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point. Trial Registration ClinicalTrials.gov Identifier: NCT04427501
Article
In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administration of chloroquine or hydroxychloroquine mostly point towards their beneficial effect. However, they may not be effective in cases with persistently high viremia, while results on ivermectin (another antiparasitic agent) are not yet available. Interestingly, azithromycin, a macrolide antibiotic in combination with hydroxychloroquine, might yield clinical benefit as an adjunctive. The results of clinical trials point to the potential clinical efficacy of antivirals, especially remdesivir (GS-5734), lopinavir/ritonavir, and favipiravir. Other therapeutic options that are being explored involve meplazumab, tocilizumab, and interferon type 1. We discuss a number of other drugs that are currently in clinical trials, whose results are not yet available, and in various instances we enrich such efficacy analysis by invoking historic data on the treatment of SARS, MERS, influenza, or in vitro studies. Meanwhile, scientists worldwide are seeking to discover novel drugs that take advantage of the molecular structure of the virus, its intracellular life cycle that probably elucidates unfolded-protein response, as well as its mechanism of surface binding and cell invasion, like angiotensin converting enzymes-, HR1, and metalloproteinase inhibitors.
Article
Antiphospholipid syndrome (APS) is an autoantibody-mediated acquired thrombophilia. It is characterized by the presence of antiphospholipid antibodies (APL) that are directed against phospholipid-binding plasma proteins, such as beta-2-glycoprotein I (b2GPI). Its main manifestations are recurrent vascular thromboses (so-called “thrombotic APS”) and pregnancy complications (“obstetric APS”). According to the current consensus criteria, a persistently positive functional lupus anticoagulant (LA) assay and/or the presence of anti-b2GPI and/or anti-cardiolipin antibodies, together with clinical symptoms, is mandatory for the diagnosis of APS. Other clinical features, such as thrombocytopenia, Coombs-positive haemolytic anaemia, heart valve disease, renal microangiopathy and neurologic disorders are also common in APL-positive patients. APS can be associated with other autoimmune disorders, such as systemic lupus erythematosus. In rare cases, catastrophic APS (CAPS) occurs, with the development of excessive thrombosis at multiple sites, usually affecting small vessels and leading to multi-organ dysfunction and organ failure. Treatment usually comprises antithrombotic therapy using antiplatelet and anticoagulant agents. However, there is no consensus concerning the intensity or duration of therapy. Despite apparently adequate anticoagulation, the risk of recurrent thrombosis remains high. For patients with CAPS, a combined therapeutic approach that includes anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulin seems to be the best treatment option. Keywords: Antiphospholipid syndrome, lupus anticoagulants, anti-cardiolipin, anti-beta-2-glycoprotein I, vascular thrombosis, pregnancy complication
Article
The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2 domains responsible for virus binding and fusion, respectively. The S1 contains a receptor-binding domain (RBD) that can specifically bind to angiotensin-converting enzyme 2 (ACE2), the receptor on target cells. Here we show that a recombinant fusion protein (designated RBD-Fc) containing 193-amino acid RBD (residues 318-510) and a human IgG1 Fc fragment can induce highly potent antibody responses in the immunized rabbits. The antibodies recognized RBD on S1 domain and completely inhibited SARS-CoV infection at a serum dilution of 1:10,240. Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2. This suggests that RBD can induce highly potent neutralizing antibody responses and has potential to be developed as an effective and safe subunit vaccine for prevention of SARS.
Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial
CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Respir Med 2021; 9(3):295-304.
Wangkanont protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine
  • B Shanmugaraj
  • K Siriwattananon
Shanmugaraj B, Siriwattananon K, Wangkanont protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine. Biochem Biophys Res Commun 2004; 324(2):773-81.
Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19)
K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. 2020; 38(1):10-18.