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)
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.
The Lancet Respiratory Medicine, 2021
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A Randomized Placebo-Controlled Trial of Sarilumab in Hospitalized Patients with Covid-19
2021
ABSTRACTBACKGROUNDSarilumab (anti-interleukin-6 receptor-α monoclonal antibody) may attenuate the inflammatory response in Covid-19.METHODSWe performed an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous sarilumab 200 mg or 400 mg in adults hospitalized with Covid-19. The phase 3 primary analysis population (cohort 1) was patients with critical Covid-19 receiving mechanical ventilation (MV) randomized to sarilumab 400 mg or placebo. The primary end point for phase 3 was the proportion of patients with ≥1-point improvement in clinical status from baseline to day 22.RESULTSFour-hundred fifty-seven (457) and 1365 patients were randomized and treated in phases 2 and 3, respectively. Among phase 3 critical patients receiving MV (n=289; 34.3% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive not receiving MV) at day 22 was 43.2% in sarilumab 400 mg and 35.5% in placebo (risk difference [RD] +7.5%; 95% confidence i...
SVU-International Journal of Medical Sciences, 2022
Background: The radiologic pulmonary inflammatory index (PII) may be used as an early predictor of inflammation as laboratory assessments in COVID-19 cases. The purpose of this study was to compare the clinical and radiological features between cases of COVID-19 necessitating admittance to the intensive care unit (ICU) and those who did not, and to correlate the PII with other inflammatory markers and outcomes. Patients and methods: 72 patients consecutively admitted with confirmed COVID-19. Their electronic records were retrospectively revised and the demographic, clinical, laboratory (complete blood count, C-reactive protein, D dimer, and serum ferritin), High resolution computed tomography (HRCT) data, PII, and the outcomes of the patients were analyzed. Results: They were 50/50%, males/females, with mean age 47.1 ± 16.8 years. During their stay, 15.3% necessitated ICU admittance, 68% cured and discharged, 9 cases referred and 6.9% died. The baseline lesions identified were ground-glass opacification recognized in (93%), higher PII and >3 lobes affection was considerably recorded in those who required ICU admittance (P= 0.041 and 0.013). There was a mild positive correlation between PII with age (r=0.264, P=0.031) and other prognostic inflammatory indicators as ferritin (r=0.225, P=0.048), D Dimer (r=0.271, P=0.043), and serum creatinine. Conclusions: The use of PII together with clinical and laboratory data may be valuable in defining the inflammatory state of COVID-19. This may allow clinicians to avoid the progression of the illness and improve the cure rates by proper early intervention.
The Lancet Infectious Diseases, 2021
Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.