Current topics in microbiology and immunology最新文献

{"title":"HemoClear: A Practical and Cost-Effective Alternative to Conventional Convalescent Plasma Retrieval Methods.","authors":"Arno Nierich, Rosita Bihariesingh, Rakesh Bansie","doi":"10.1007/82_2024_276","DOIUrl":"https://doi.org/10.1007/82_2024_276","url":null,"abstract":"<p><p>Convalescent plasma has increasingly been used to treat various viral infections and confer post-exposure prophylactic protection during the last decade and has demonstrated favorable clinical outcomes in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the recent COVID-19 pandemic. The pandemic has highlighted the need for cost-effective, accessible, and easy-to-use alternatives to conventional blood plasmapheresis techniques, allowing hospitals to become more self-sufficient in harvesting and transfusing donor plasma into recipients in a single setting. To this end, the use of a membrane-based bedside plasmapheresis device (HemoClear) was evaluated in an open-label, non-randomized prospective trial in Suriname in 2021, demonstrating its practicality and efficacy in a low-to middle-income country. This paper will review the use of this method and its potential to expedite the process of obtaining convalescent plasma, especially during pandemics and in resource-constrained settings.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibody Therapies Against SARS-CoV-2: Promises and Realities.","authors":"Daniele Focosi","doi":"10.1007/82_2024_268","DOIUrl":"https://doi.org/10.1007/82_2024_268","url":null,"abstract":"<p><p>Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 have been widely deployed in the ongoing COVID-19 pandemic. I review here the impact of those therapeutics in the early pandemic, ranging from structural classification to outcomes in clinical trials to in vitro and in vivo evidence of basal and treatment-emergent immune escape. Unfortunately, the Omicron variant of concern has completely reset all achievements so far in mAb therapy for COVID-19. Despite the intrinsic limitations of this strategy, future developments such as respiratory delivery of further engineered mAb cocktails could lead to improved outcomes.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convalescent Plasma for Immunocompromised Patients.","authors":"Shmuel Shoham","doi":"10.1007/82_2024_272","DOIUrl":"https://doi.org/10.1007/82_2024_272","url":null,"abstract":"<p><p>COVID-19 convalescent plasma (CCP) is an important therapeutic option for immunocompromised patients with COVID-19. Such patients are at increased risk for serious complications of infection and may also develop a unique syndrome of persistent infection. This article reviews the rationale for CCP utilization in immunocompromised patients and the evidence for its value in immunosuppressed patients with both acute and persistent COVID-19. Both historical precedence and understanding of the mechanisms of action of antibody treatment support this use, as do several lines of evidence derived from case series, comparative studies, randomized trials, and systematic reviews of the literature. A summary of recommendations from multiple practice guidelines is also provided.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generating the Evidence Base for Convalescent Plasma Use for a New Infectious Disease.","authors":"Hyunah Yoon, Liise-Anne Pirofski","doi":"10.1007/82_2024_275","DOIUrl":"https://doi.org/10.1007/82_2024_275","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept across the world in the waning months of 2019 and emerged as the cause of the coronavirus disease 19 (COVID-19) pandemic in early 2020. The use of convalescent plasma (CP) for prior respiratory pandemics provided a strong biological rationale for the rapid deployment of COVID-19 convalescent plasma (CCP) in early 2020 when no validated treatments or prior immunity existed. CCP is an antiviral agent, with its activity against SARS-CoV-2 stemming from specific antibodies elicited by the virus. Early efforts to investigate the efficacy of CCP in randomized clinical trials (RCTs) that targeted hospitalized patients with COVID-19 did not demonstrate the overall efficacy of CCP despite signals of benefit in certain subgroups, such as those treated earlier in disease. In contrast, studies adhering to the principles of antibody therapy in their study design, choice of patient population, and product qualification, i.e., those that administered high levels of specific antibody during the viral phase of disease in immunocompromised or very early in immunocompetent individuals, demonstrated benefits. In this chapter, we leverage the knowledge gained from clinical studies of CCP for COVID-19 to propose a framework for future studies of CP for a new infectious disease. This framework includes obtaining high-quality CP and designing clinical studies that adhere to the principles of antibody therapy to generate a robust evidence base for using CP.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Importance of Geographic Proximity of Convalescent Plasma Donors.","authors":"Katie L Kunze, Patrick W Johnson","doi":"10.1007/82_2024_270","DOIUrl":"https://doi.org/10.1007/82_2024_270","url":null,"abstract":"<p><p>Donor-recipient proximity emerged as an important factor influencing the efficacy of COVID-19 convalescent plasma (CCP) treatment during the early stages of the COVID-19 pandemic. This relationship was uncovered while analyzing data collected in the collaborative Expanded Access Program (EAP) for CCP at Mayo Clinic, a project aimed to establish protocols for CCP use amid the uncertainty of the novel disease. Analysis of data from nearly 28,000 patients revealed a significant reduction in risk of 30-day mortality for those receiving near-sourced plasma when compared to those receiving distantly sourced plasma [pooled relative risk, 0.73 (95% CI 0.67-0.80)], prompting adjustments in treatment protocols at selected institutions, and highlighting the importance of proximity in optimizing CCP outcomes. Despite its significance, subsequent studies of CCP effectiveness in COVID-19 have often overlooked donor-recipient proximity. Our findings emphasize the importance of donor-recipient proximity in CCP treatment in the current pandemic, and we discuss potential methods for improving CCP efficacy in future pandemics. Our recommendations include prioritizing virus genotyping for vulnerable patients, establishing a robust testing infrastructure, and collecting additional donor data to enhance plasma selection. This chapter underscores the importance of comprehensive data collection and sharing to navigate the evolving landscape of newly emerging infectious diseases.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convalescent Plasma and Other Antibody Therapies for Infectious Diseases-Lessons Learned from COVID-19 and Future Prospects.","authors":"David J Sullivan","doi":"10.1007/82_2024_273","DOIUrl":"10.1007/82_2024_273","url":null,"abstract":"<p><p>Antiviral passive antibody therapy includes convalescent plasma, hyperimmune globulin, and monoclonal antibodies. Passive antibodies have proven effective in reducing morbidity and mortality for SARS-CoV-2 and other infectious diseases when given early in the disease course with sufficiently high specific total and neutralizing antibody levels. Convalescent plasma can be delivered to patients before vaccination implementation or novel drug production. Carefully designed and executed randomized controlled trials near the pandemic outset are important for regulatory bodies, healthcare workers, guideline committees, the public, and the government. Unfortunately, many otherwise well-designed antibody-based clinical trials in COVID-19 were futile, either because they intervened too late in the disease or provided plasma with insufficient antibodies. The need for early treatment mandates outpatient clinical trials in parallel with inpatient trials. Early outpatient COVID-19 convalescent plasma transfusion with high antibody content within 9 days of symptom onset has proven effective in blunting disease progression and reducing hospitalization, thus reducing hospital overcrowding in a pandemic. Convalescent plasma offers the opportunity for hope by enabling community participation in outpatient curative therapy while monoclonal therapies, vaccines, and drugs are being developed. Maintaining the appropriate infrastructure for antibody infusion in both outpatient and inpatient facilities is critical for future pandemic readiness.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Patient Advocate During a Pandemic: The Case of Convalescent Plasma.","authors":"Chaim Lebovits","doi":"10.1007/82_2024_271","DOIUrl":"https://doi.org/10.1007/82_2024_271","url":null,"abstract":"<p><p>The onset of the COVID-19 pandemic confronted medicine with several difficulties, including a lack of specific therapeutic options, the absence of out-of-hospital testing facilities to diagnose the condition, and the sudden extraordinary need for intensive medical care that overwhelmed most hospitals. Early in the pandemic, many physicians recognized that using antibodies harvested from recovering patients was a treatment that had a proven track record for many diseases and that might be used to manage the disease at least as a stopgap until more specific medicines for COVID-19 were developed. But using convalescent plasma raised many additional complications, most especially the logistics that needed to be put in place to collect and distribute such plasma. Unlike drugs ordered from a pharmacy, plasma and other blood products are procured by a complex process that depends intensely on interaction with the public, the provider of all blood products that are directly provided to patients. Blood components such as convalescent plasma, intended to be used immediately without major processing, are entirely supplied by donations from the public. This form of treatment can therefore benefit from patient advocates, especially if they are experienced in solving problems of logistics and in the process of matching supply to demand that is more commonly encountered in the business world than in medicine. In this chapter, one patient advocate, Chaim Lebovits, describes the process of mobilizing the population, interacting with blood banks and hospitals, and successfully channeling thousands of units of plasma from volunteers recovering from COVID-19 to patients in hospitals. Starting in New York City in early 2020 and initially working with communities with which Mr. Lebovits was familiar, the efforts steadily spread across many parts of the US. The model described here, which uses patient advocates to serve as a link between patients, blood banks, and hospitals in the service of gathering and distributing high-titer convalescent plasma to patients is likely to be relevant to the next pandemic.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperimmune Globulins in COVID-19.","authors":"Yasmin Maor, Oren Zimhony","doi":"10.1007/82_2024_277","DOIUrl":"https://doi.org/10.1007/82_2024_277","url":null,"abstract":"<p><p>The COVID-19 pandemic, resulting from the emergence of the novel coronavirus SARS-CoV-2, posed unprecedented challenges to global health systems as no proven therapy was available. Initially, COVID-19 convalescent plasma (CCP) from recovered COVID-19 patients showed promise as a therapeutic option. However, the efficacy of this approach was closely correlated with the neutralizing antibody titer in the administered plasma and thus effectiveness was not always guaranteed. In response, hyperimmune immunoglobulins (hIG) derived from CCP obtained by apheresis from recovered or vaccinated individuals emerged as a potential alternative. hIG were purified through stringent chromatographic processing from CCP units and displayed varying results in clinical trials, although it seems likely that they improved outcomes compared to placebo or CCP at day 28, particularly in unvaccinated patients. The variability in the effect of hIG likely stems from factors such as the timing of outcome assessment, the administered dose of hIG, the patients' immunological background, and the matching between the variant infecting patients and the neutralization ability of the immunoglobulin batch, which depended on the timing of the CCP collection. Despite logistical challenges and high production costs, hIG showcase advantages over CCP, offering versatility in administration routes and eliminating the need for blood matching, thus facilitating administration in the community, and allowing for variant-specific preparations. hIG appear to be of particular importance in the treatment of immunocompromised patients and patients with persistent COVID-19, although studies in these populations are lacking. Non-human alternatives, such as equine-derived hIG and recombinant hIG, may provide a solution to the logistical challenges of large-scale hIG preparation. Further study is needed to explore these avenues. Establishing the infrastructure for large-scale hIG production independent of plasma donations emerges as a strategic approach for future pandemics, justifying exploration and promotion by health authorities.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibodies and Hyperimmune Immunoglobulins in the Next Pandemic.","authors":"Massimo Franchini, Daniele Focosi","doi":"10.1007/82_2024_274","DOIUrl":"https://doi.org/10.1007/82_2024_274","url":null,"abstract":"<p><p>Pandemics are highly unpredictable events that are generally caused by novel viruses. There is a high likelihood that such novel pathogens belong to entirely novel viral families for which no targeted small-molecule antivirals exist. In addition, small-molecule antivirals often have pharmacokinetic properties that make them contraindicated for the frail patients who are often the most susceptible to a novel virus. Passive immunotherapies-available from the first convalescent patients-can then play a key role in controlling pandemics. Convalescent plasma is immediately available, but if manufacturers have fast platforms to generate marketable drugs, other forms of passive antibody treatment can be produced. In this chapter, we will review the technological platforms for generating monoclonal antibodies and hyperimmune immunoglobulins, the current experience on their use for treatment of COVID-19, and the pipeline for pandemic candidates.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convalescent Plasma and the US Expanded Access Program: A Personal Narrative.","authors":"Michael J Joyner","doi":"10.1007/82_2024_269","DOIUrl":"https://doi.org/10.1007/82_2024_269","url":null,"abstract":"<p><p>Between early April 2020 and late August 2020, nearly 100,000 patients hospitalized with SARS-CoV2 infections were treated with COVID-19 convalescent plasma (CCP) in the US under the auspices of an FDA-authorized Expanded Access Program (EAP) housed at the Mayo Clinic. Clinicians wishing to provide CCP to their patients during that 5-month period early in the COVID pandemic had to register their patients and provide clinical information to the EAP program. This program was utilized by some 2,200 US hospitals located in every state ranging from academic medical centers to small rural hospitals and facilitated the treatment of an ethnically and socio-economically diverse cross section of patients. Within 6 weeks of program initiation, the first signals of safety were found in 5,000 recipients of CCP, supported by a later analysis of 20,000 recipients (Joyner et al. in J Clin Invest 130:4791-4797, 2020a; Joyner et al. in Mayo Clin Proc 95:1888-1897, 2020b). By mid-summer of 2020, strong evidence was produced showing that high-titer CCP given early in the course of hospitalization could lower mortality by as much as a third (Joyner et al. in N Engl J Med 384:1015-1027, 2021; Senefeld et al. in PLoS Med 18, 2021a). These data were used by the FDA in its August decision to grant Emergency Use Authorization for CCP use in hospitals. This chapter provides a personal narrative by the principal investigator of the EAP that describes the events leading up to the program, some of its key outcomes, and some lessons learned that may be applicable to the next pandemic. This vast effort was a complete team response to a crisis and included an exceptional level of collaboration both inside and outside of the Mayo Clinic. Writing just 4 years after the initiation of the EAP, this intense professional effort, comprising many moving parts, remains hard to completely understand or fully explain in this brief narrative. As Nelson Mandela said of the perception of time during his decades in prison, \"the days seemed like years, and the years seemed like days.\"</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}