[Experience of olokizumab use in COVID-19 patients].
15 Dec 2020-Terapevticheskii Arkhiv ("Consilium Medicum" Publishing house)-Vol. 92, Iss: 12, pp 148-154
TL;DR: Artlegia (olokizumab) is a humanized monoclonal antibody belonging to the G4/Kappa immunoglobulin isotype that selectively binds to human IL-6 and effectively neutralizes it.
Abstract: Most subjects with the COVID-19 experience mild to moderate symptoms, but approximately 10% of cases suffer from severe course of disease IL-6 inhibitors are actively used to neutralize and prevent the «cytokine storm» Olokizumab is a humanized monoclonal antibody belonging to the G4/Kappa immunoglobulin isotype that selectively binds to human IL-6 and effectively neutralizes it Aim To evaluate the efficacy and safety of Artlegia (olokizumab) for the treatment of subjects with a disease caused by the SARS-COV-2 virus in a real-world clinical setting Materials and methods The analysis included data of 610 subjects aged 5508±1268 years who received olokizumab at a single dose of 160 mg/mL – 04 mL subcutaneously as a preemptive anti-inflammatory therapy The comparison group included 511 subjects aged 5523±1123 years who received standard therapy without IL-6 inhibitors Control Endpoints: 1 Positive clinical changes on Day 7 2 Changes in the CRP levels on Days 1, 2, and 7 3 Duration of oxygen therapy 4 Number of days in hospital 5 Number of adverse events 6 Disease outcome Results If a «cytokine storm» occurs, immune regulatory events will trigger the development of either a protective immune response or an exacerbated inflammatory response The use of preemptive anti-inflammatory therapy has both a short-term and, most importantly, a long-term effect on the T and B parts of the immune process These aspects definitely require further research and observation Conclusion The use of olokizumab to treat the new COVID-19 coronavirus disease has demonstrated a positive effect on clinical and laboratory parameters Primarily, it affects the severity of clinical parameters by improving the general condition already on the first day of observation, and decreasing body temperature to normal values The changes in the C-reactive protein levels show a significant effect of the IL-6 inhibitor on the systemic inflammatory response
Citations
More filters
••
TL;DR: In this paper , the authors reviewed the pleiotropic roles of the IL-6 pathway in lung damage and ARDS in severe COVID-19, and the rationale for IL6 signaling blockade at different levels.
23 citations
••
TL;DR: In this article , the authors examined new data on efficacy and safety of OKZ in RA and the prospects of its use in rheumatology ǫ using a clinical trial.
Abstract: Rheumatoid arthritis (RA) is a chronic immune-mediated rheumatic diseases (IMRDs) manifested with progressive destruction of joints, systemic inflammation of visceral organs and a wide range of co-morbidities associated with chronic inflammation. Among the cytokines involved in the pathogenesis of RA and certain other IMRDs, the role of interleukin (IL) 6 is of special interest. The introduction of mAbs tocilizumab (TCZ) and later sarilumab (SAR), both blocking the receptor of this cytokine, into clinical practice was an important achievement in the treatment of IIRDs at the beginning of the 21st century. As a novel approach in the treatment of RA, the humanized mAb against IL-6 olokizumab (OKZ) is in development by the Russian company R-PHARM under the license agreement with UCB Pharma. The review examines new data on efficacy and safety of OKZ in RA and the prospects of its use in rheumatology
3 citations
••
TL;DR: This systematic overview of possible SARS-CoV-2 therapeutic strategies from 2019 to 2022 indicates three potential targets: virus entry, virus replication, and the immune system to aid the development of more potent and specific antiviral compounds.
Abstract: Coronavirus disease 2019 is a rather heterogeneous disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing pandemic is a global threat with increasing death tolls worldwide. SARS-CoV-2 belongs to lineage B β-CoV, a subgroup of Sarbecovirus. These enveloped, large, positive-sense single-stranded RNA viruses are easily spread among individuals, mainly via the respiratory system and droplets. Although the disease has been gradually controlled in many countries, once social restrictions are relaxed the virus may rebound, leading to a more severe and uncontrollable situation again, as occurred in Shanghai, China, in 2022. The current global health threat calls for the urgent development of effective therapeutic options for the treatment and prevention of SARS-CoV-2 infection. This systematic overview of possible SARS-CoV-2 therapeutic strategies from 2019 to 2022 indicates three potential targets: virus entry, virus replication, and the immune system. The information provided in this review will aid the development of more potent and specific antiviral compounds.
2 citations
••
TL;DR: In this paper , a review focused on the most common and currently studied monoclonal antibody drugs, as well as up-to-date data on the pathogenesis of COVID-19, host immune response against SARS-CoV-2 and its association with cytokine storm.
Abstract: Coronavirus infection can have various degrees of severity and outcomes. In some cases, it causes excessive production of pro-inflammatory cytokines, a so-called cytokine storm, leading to acute respiratory distress syndrome. Unfortunately, the exact pathophysiology and treatment, especially for severe cases of COVID-19, are still uncertain. Results of preliminary studies showed that immunosuppressive therapy, such as interleukin (IL)-6, IL-1, and TNF-α antagonists commonly used in rheumatology, can be considered as treatment options for COVID-19, especially in severe cases. The review focused on the most common and currently studied monoclonal antibody drugs, as well as up-to-date data on the pathogenesis of COVID-19, host immune response against SARS-CoV-2 and its association with cytokine storm. It also covered effects of interleukin (IL)-6, IL-1, and TNF-α blockers on the course of coronavirus infection and outcome in patients treated for the main autoimmune disease and subsequently infected with COVID-19.
2 citations
••
TL;DR: This meta-analysis did not demonstrate statistically significant differences in the relative risks of serious adverse events and adverse events of “Infections and Invasions” class for the use of antiinterleukin drugs in COVID-19 patients.
Abstract: Objective.
To evaluate safety of anti-interleukin drugs used as a pathogenetic therapy of COVID-19 as assessed by risks of infectious complications.
Materials and Methods.
A systematic review of publications related to safety assessment of anti-interleukin drugs recommended as pathogenetic therapy in COVID-19 patients in terms of incidence of serious adverse events and adverse events of “Infections and Invasions” class and a meta-analysis of the data were performed.
Results.
The meta-analysis included 16 randomized and 3 non-randomized studies. The hazard ratio of serious adverse events between the comparison groups was 0.93 95% CI 0.85; 1.01, the hazard ratio of adverse event of “Infections and Invasions” class was 0.9 95% CI 0.8; 1.02, showing no differences in the incidence of those events.
Conclusions.
This meta-analysis did not demonstrate statistically significant differences in the relative risks of serious adverse events and adverse events of “Infections and Invasions” class for the use of antiinterleukin drugs in COVID-19 patients.
1 citations
References
More filters
••
TL;DR: An update on CoV infections and relevant diseases, particularly the host defense against CoV‐induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment is provided.
Abstract: Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.
1,416 citations
••
TL;DR: Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.
Abstract: COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases Mortality in COVID-19 patients has been linked to the presence of the so-called "cytokine storm" induced by the virus Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality
1,100 citations
••
TL;DR: An overview of the known clinical features and treatment options for COVID‐19 is provided and quarantine is the only intervention that appears to be effective in decreasing the contagion rate.
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a novel coronavirus from the same family as SARS-CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), presents flu-like symptoms which can become serious in high-risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID-19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: 'COVID-19', '2019-nCoV', 'coronavirus' and 'SARS-CoV-2'. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID-19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real-time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow-up. To date, there is no evidence of any effective treatment for COVID-19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence-based treatment modality.
900 citations
••
TL;DR: Understanding of the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute‐phase reactants, and serum biochemistry in COVID‐19 is improved.
Abstract: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute-phase reactants, and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM-, IgA-, and IgG-type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute-phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.
783 citations
••
TL;DR: While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.
Abstract: Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.
710 citations