Corrigendum: Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study (original) (raw)
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Frontiers in Immunology, 2021
BackgroundImmune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease.MethodsThirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication.ResultsWe observed reduction of serum IL-...
Frontiers in Immunology, 2021
In the last few months, the coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide and has provoked an exceptional effort from the scientific community to understand the disease. Clinical evidence suggests that severe COVID-19 is associated with both dysregulation of damage tolerance caused by pulmonary immunopathology and high viral load. In this review article, we describe and discuss clinical studies that show advances in the understanding of mild and severe illness and we highlight major points that are critical for improving the comprehension of different clinical outcomes. The understanding of pulmonary immunopathology will contribute to the identification of biomarkers in an attempt to classify mild, moderate, severe and critical COVID-19 illness. The interface of pulmonary immunopathology and the identification of biomarkers are critical for the development of new therapeutic strategies aimed to reduce the systemic and pulmonary hyperinflammat...
Acta Informatica Medica, 2023
Background: The pathophysiology and therapy of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are a dilemma for scientists and health professionals, and the fact that patients show different symptoms and severity of the clinical picture also contributes to that. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of immunomodulators) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring inflammatory markers (ESR and CRP), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Inflammatory markers [ESR (erythrocyte sedimentation rate), CRP (C-reactive protein)] were examined on three occasions: twice during hospitalization and once after hospital discharge. Immunomodulators used intrahospital were corticosteroids (methylprednisolone, dexamethasone, methylprednisolone + dexamethasone), tocilizumab or metenkefalin/tridecactide. Posthospital, patients were taking either methylprednisolone or did not use any immunomodulators. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis and Wilcoxon Signed-Rank) were applied and effect size (ES) was calculated. Results: Three corticosteroid therapies used intrahospital caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture, but the ES was the biggest with methylprednisolone + dexamethasone, then dexamethasone, and lastly methylprednisolone. Posthospital, methylprednisolone caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture. The most common comorbidity in all patients, as well as in patients with a severe clinical picture, was hypertension. There was no statistically significant impact of the number of comorbidities patients had on ESR and CRP, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of immunomodulators, especially methylprednisolone + dexamethasone intrahospital and methylprednisolone posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease’s pathophysiology and the immune response. There is also a positive correlation between the number of comorbidities patients have and the severity of the clinical picture.
Revista da Associação Médica Brasileira
Neutralizing monoclonal antibody (mAb) therapies targeting with high specificity to SARS-CoV-2 has been considered as one of the potential therapies for COVID-19 since the beginning of the pandemic. Preclinical studies demonstrated a marked reduction in viral loads in the upper and lower respiratory tract with the use of neutralizing mAbs 1. The mAbs have the ability to coordinate the immune defense to link to the virus and control the virus load. The mAbs are defined as an antibody derived from a single B-cell clone and recognize a single and unique epitope that can link to their specific epitope on target antigens and can mediate multiple effects such as disruption of the function and eliminate cells or pathogens 2. These mAbs for COVID-19 are fully human and were discovered from COVID-19 patient' donors, and one of their targets is to block the S protein of the SARS-CoV-2, preventing viral entry into host cells 3. The U.S. Food and Drug Administration (FDA) issued an emergency use authorization for mAbs to be used as pre-exposure prophylaxis and mild-moderate COVID-19. However, given to the Omicron variant, the FDA did not recommend using casirivimab+imdevimab. In Brazil, mAbs were approved by the Brazilian regulatory agency, i.e., The National Health Surveillance Agency (ANVISA), for use in patients with mild-to-moderate nonhospitalized COVID-19 patients and for the prevention of COVID-19 infection. This systematic review aimed to identify, describe, evaluate, and synthesize evidence of effectiveness of mAbs in clinical outcomes in COVID-19 patients. METHODS This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations 4. Eligibility criteria The study protocol followed the patients of interest, intervention to be studied, comparison of interventions, and outcome of interest (PICO) methodology. With the use of a mAb as the main study point, the PICO framework was as follows: patients, adult COVID-19 patients; intervention, use of an mAb (casiriv-imab+imdevimab, bamlanivimab, bamlanivimab+etesevimab, sotrovimab, regdanvimab, and tixagevimab+cilgavimab); comparison between the standard of care (SOC) and placebo; and outcome, symptomatic COVID-19 infection, symptom resolution, adverse event, severe adverse event, hospitalization, and the mortality rate due to any cause in 29 days. The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews: CRD42022320972. All phase 3 randomized controlled trials (RCTs) on the topic were included. No restrictions were imposed with regard to the date of publication, language, or availability of the full text of the article. Information sources and search strategy Two authors developed a search strategy that was revised and approved by the team, selected information sources, and systematically searched MEDLINE, EMBASE, Central Cochrane, and ClinicalTrials.gov. Specific search strategies were used for each database:
Frontiers in Immunology, 2020
In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, we feel a duty to share our experience and our knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.
Infectious Diseases and Therapy
Introduction: SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS). Methods: We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/ kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale C 3) up to day 15. Results: A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score C 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48-2.20). No relevant safety issues were identified. Conclusions: In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.
The impact of COVID-19 monoclonal antibodies on clinical outcomes: A retrospective cohort study
American Journal of Health-System Pharmacy
Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. Methods A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 1...
Immunomodulatory approaches in managing lung inflammation in COVID-19: A double-edge sword
Introduction: The novel coronavirus infectious disease 2019 (COVID-19) which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a gigantic problem. The lung is the major target organ of SARS-CoV-2 and some of its variants like Delta and Omicron variant adapted in such a way that these variants can significantly damage this vital organ of the body. These variants raised a few eyebrows as the outbreaks have been seen in the vaccinated population. Patients develop severe respiratory illnesses which eventually prove fatal unless treated early. Main Body: Studies have shown that SARS-CoV-2 causes the release of proinflammatory cytokines such as interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α which are mediators of lung inflammation, lung damage, fever, and fibrosis. Additionally, various chemokines have been found to play an important role in the disease progression. A plethora of pro-inflammatory cytokines "cytokine storm" has been observed in severe cases of SARS-CoV-2 infection leading to acute respiratory distress syndrome (ARDS) and pneumonia that may prove fatal. To counteract cytokine storm-inducing lung inflammation, several promising immunomodulatory approaches are being investigated in numerous clinical trials. However, the benefits of using these strategies should outweigh the risks involved as the use of certain immunosuppressive approaches might lead the host susceptible to secondary bacterial infections. Conclusion: The present review discusses promising immunomodulatory approaches to manage lung inflammation in COVID-19 cases which may serve as potential therapeutic options in the future and may prove lifesaving.
Research Square - Research Square, 2022
Background: Monoclonal antibody (mAb) treatment for COVID-19 is associated with improved clinical outcomes. However, there is limited information regarding the impact of treatment on symptoms and the prevalence of post-COVID Conditions (PCC). Understanding of the association between time to mAb infusion and the development of PCC is also limited. Methods: This longitudinal study was conducted among patients with COVID-19 who received mAb infusions at a Federally Quali ed Health Center in San Diego, CA. A series of telephone interviews were conducted at baseline and follow-up (14 days and 28+ days). A comprehensive symptom inventory was completed, and physical and mental health status were measures using PROMIS-29 and PHQ-2. Pearson's Chi-squared tests and independent two-sample t-tests were performed to test for association between time to mAb infusion and outcomes at follow-up. A Poisson regression model was used to analyze whether time to mAb infusion predicts risk of developing PCC. Results: Participants (N=411) were 53% female, ranged in age from 16 to 92 years (mean 50), and a majority (56%) were Latino/Hispanic. Cross-sectional ndings revealed a high symptom burden at baseline (70% of patients had cough, 50% had fever, and 44% had headache). The prevalence of many symptoms decreased substantially by the nal follow-up survey (29% of patients had cough, 3% had fever, and 28% had headache). Longitudinal ndings indicated that 10 symptoms decreased in prevalence from baseline to nal follow-up, 2 remained the same, and 14 increased. The severity of symptoms and most patient-reported physical and mental health measure scores decreased over time. The prevalence of PCC was 69% when PCC was de ned as ≥1 symptom at nal follow-up. Time to mAb infusion was not signi cantly associated with any outcome at follow-up. Time to infusion was not associated with PCC status at nal follow-up in the crude or adjusted Poisson regression models. Conclusions: The prevalence of PCC was high among this patient population following COVID-19 mAb treatment. Time to mAb infusion did not predict the development of PCC. Further research in these areas is essential to answer urgent clinical questions about effective treatments of COVID-19.
The Journal of Infectious Diseases, 2023
Background. Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. Methods. Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), antinucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. Results. Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma NAg compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. Conclusions. Our study suggests that nmAb has an antiviral effect assessed by plasma NAg among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. Clinical Trials Registration. NCT04501978.