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Annals of Internal Medicine Sep 2022The Association for the Advancement of Blood and Biotherapies reported a thorough analysis of existing data and guidelines for the use of COVID-19 convalescent plasma...
The Association for the Advancement of Blood and Biotherapies reported a thorough analysis of existing data and guidelines for the use of COVID-19 convalescent plasma (CCP) for treatment and prophylaxis of COVID-19. The editorialists discuss the recommendations, how they compare with recommendations from other entities, and the lessons the experience with CCP provides for the use of passive immunotherapy for future emerging infectious diseases.
Topics: COVID-19; Humans; Immunization, Passive; SARS-CoV-2; Treatment Outcome; COVID-19 Serotherapy
PubMed: 35969864
DOI: 10.7326/M22-2329 -
The New England Journal of Medicine May 2022Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.
METHODS
In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion.
RESULTS
Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized.
CONCLUSIONS
In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).
Topics: Adult; Ambulatory Care; COVID-19; Disease Progression; Double-Blind Method; Hospitalization; Humans; Immunization, Passive; Treatment Outcome; United States; COVID-19 Serotherapy
PubMed: 35353960
DOI: 10.1056/NEJMoa2119657 -
The New England Journal of Medicine Nov 2020
Topics: COVID-19; Humans; Hydroxychloroquine; Immunization, Passive; Pandemics; COVID-19 Serotherapy
PubMed: 33252875
DOI: 10.1056/NEJMe2034094 -
Seminars in Nuclear Medicine Jan 2022SARS-CoV-2 virus may cause COVID-19 disease, which causes mild-to-moderate disease in 80% of laboratory-confirmed cases which may be community-managed. A considerable... (Review)
Review
SARS-CoV-2 virus may cause COVID-19 disease, which causes mild-to-moderate disease in 80% of laboratory-confirmed cases which may be community-managed. A considerable age-dependent mortality is seen among elderly and other at-risk populations but among young and healthy individuals it is < 0.5%. Long-term health issues have been reported following severe COVID-19 requiring hospitalization as well as after cases of mild COVID-19 without hospitalization. Upon receiving COVID-19 suspected patients at hospitals, patients should be isolated and PPE should be worn by all health staff when in contact with the patients. Additionally, patients are tested for the presence of SARS-CoV-2 RNA by PCR, and blood samples are drawn. Imaging is not pivotal for the diagnosis, but chest X-ray is a relevant examination for all and is used to determine severity and treatment need Abnormal findings on CT scans are found in most patients, most frequently peripheral ground-glass opacity and bilateral patchy shadowing are present. Patients are, according to their needs and risks, treated with oxygen therapy, anticoagulation therapy, steroids, antivirals, or immunosupressive drugs on special indications. Convalescent plasma therapy and monoclonal antibodies have a limited role in the treatment, mostly in severely immunocompromised patients. Patients with long-term sequelae should be evaluated in a post-COVID outpatient clinic. The most frequent reported symptoms include cognitive impairment, dyspnea, loss of smell and taste, and mental and physical fatigue although a wide spectrum of symptoms from other organ systems are also reported. The current treatment is based on symptom relief and rehabilitation as there is no documented specific medical treatment.
Topics: Aged; COVID-19; Humans; Immunization, Passive; RNA, Viral; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 34243904
DOI: 10.1053/j.semnuclmed.2021.06.004 -
European Journal of Medical Research Jan 2022SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this... (Review)
Review
SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Antiviral Agents; COVID-19; Clinical Trials as Topic; Dietary Supplements; Humans; Immunization, Passive; Immunoglobulins, Intravenous; Pandemics; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 35027080
DOI: 10.1186/s40001-021-00626-3 -
Transfusion Medicine (Oxford, England) Feb 2023Faced with an evolving pandemic and a lack of clarity of the role of convalescent plasma for patients with COVID-19, the CONCOR-1 trial was launched. In 14 months the...
Faced with an evolving pandemic and a lack of clarity of the role of convalescent plasma for patients with COVID-19, the CONCOR-1 trial was launched. In 14 months the trial was designed, launched, completed, and submitted for publication. In total, 72 sites in three countries served by four blood suppliers randomised 940 patients. Many enablers facilitated the trial including: three study principal investigators to distribute the trial workload, diverse steering committee members, an international data safety monitoring committee, multiple statisticians and methodologists, virtual meeting platforms, REDCap data platform, pausing of non-COVID-19 trials, rapid approval pathways for institutional review boards and regulators, centralised institutional review boards in many locations, restriction of use of convalescent plasma to trial participants and the incredible dedication by research personnel. In future pandemics, we need to be prepared for rapid launch of trials. The protocols, consent forms, data collection tools, and procedures need to be in draft form ready for use at all times. We were well-prepared for blood shortages but should have anticipated the need to conduct trials with convalescent plasma. In this short article, we detail our lessons learned to inform researchers faced with the next pandemic pathogen.
Topics: Humans; COVID-19; SARS-CoV-2; Bisoprolol; Immunization, Passive; COVID-19 Serotherapy
PubMed: 35633145
DOI: 10.1111/tme.12882 -
The New England Journal of Medicine Sep 2022
Topics: Ambulatory Care; COVID-19; Humans; Immunization, Passive; Outpatients; Plasma; COVID-19 Serotherapy
PubMed: 36069882
DOI: 10.1056/NEJMc2208338 -
The New England Journal of Medicine Sep 2022
Topics: Ambulatory Care; COVID-19; Humans; Immunization, Passive; Outpatients; Plasma; COVID-19 Serotherapy
PubMed: 36069883
DOI: 10.1056/NEJMc2208338 -
Polish Archives of Internal Medicine Sep 2021Infection with SARS-CoV-2, responsible for COVID-19, has spread all over the world since the beginning of 2020. Healthcare providers and researchers have been... (Review)
Review
Infection with SARS-CoV-2, responsible for COVID-19, has spread all over the world since the beginning of 2020. Healthcare providers and researchers have been overwhelmed not only by the rapid diffusion of the disease resulting in a pandemic with more than 4 million cases of death, but also by the lack of therapeutic options. After more than 1 year, the knowledge on COVID-19 has increased thanks to the enormous effort of the scientific community. To date, some algorithms of management have been adopted. While asymptomatic or mildly symptomatic patients should receive only a symptom-based treatment and clinical monitoring when necessary, inpatients could be candidates for antiviral treatment due to fully symptomatic disease. Corticosteroid treatment should be limited to patients with severe disease, particularly those with respiratory failure or acute respiratory distress syndrome. Since the main clinical features of COVID-19 are hypoxemia and dyspnea, oxygen therapy remains the cornerstone of managing more severe cases. In this context, the first-line approach should be represented by low-flow oxygen delivery via a nasal cannula or, more frequently, via a face mask with a known fraction of inspired oxygen. When low-flow oxygen fails to significantly improve oxygen saturation, oxygen therapy using a high-flow nasal cannula is recommended. The current challenges in the treatment of COVID-19 include the need to define the role of convalescent plasma and monoclonal antibodies as well as to identify the optimal target and time for anticoagulation. In this review, we highlight the main aspects of these challenges in light of recent updates.
Topics: COVID-19; Coronavirus Infections; Humans; Immunization, Passive; Pandemics; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 34590451
DOI: 10.20452/pamw.16077 -
Stem Cell Research & Therapy Nov 2023Immunologically impaired individuals respond poorly to vaccines, highlighting the need for additional strategies to protect these vulnerable populations from COVID-19....
BACKGROUND
Immunologically impaired individuals respond poorly to vaccines, highlighting the need for additional strategies to protect these vulnerable populations from COVID-19. While monoclonal antibodies (mAbs) have emerged as promising tools to manage infectious diseases, the transient lifespan of neutralizing mAbs in patients limits their ability to confer lasting, passive prophylaxis from SARS-CoV-2. Here, we attempted to solve this problem by combining cell and mAb engineering in a way that provides durable immune protection against viral infection using safe and universal cell therapy.
METHODS
Mouse embryonic stem cells equipped with our FailSafe™ and induced allogeneic cell tolerance technologies were engineered to express factors that potently neutralize SARS-CoV-2, which we call 'neutralizing biologics' (nBios). We subcutaneously transplanted the transgenic cells into mice and longitudinally assessed the ability of the cells to deliver nBios into circulation. To do so, we quantified plasma nBio concentrations and SARS-CoV-2 neutralizing activity over time in transplant recipients. Finally, using similar cell engineering strategies, we genetically modified FailSafe™ human-induced pluripotent stem cells to express SARS-CoV-2 nBios.
RESULTS
Transgenic mouse embryonic stem cells engineered for safety and allogeneic-acceptance can secrete functional and potent SARS-CoV-2 nBios. As a dormant, subcutaneous tissue, the transgenic cells and their differentiated derivatives long-term deliver a supply of protective nBio titers in vivo. Moving toward clinical relevance, we also show that human-induced pluripotent stem cells, similarly engineered for safety, can secrete highly potent nBios.
CONCLUSIONS
Together, these findings show the promise and potential of using 'off-the-shelf' cell products that secrete neutralizing antibodies for sustained protective immunity against current and future viral pathogens of public health significance.
Topics: Humans; Animals; Mice; COVID-19; SARS-CoV-2; Antibodies, Viral; Antibodies, Neutralizing; Immunization, Passive; Antibodies, Monoclonal
PubMed: 37932852
DOI: 10.1186/s13287-023-03556-5