A Brief History of Polyclonal Antibody Therapies Against Bacterial and Viral Diseases Before COVID-19.

The use of the serum or plasma of patients or animals who have recovered from an infectious disease, or had been immunized with a relevant antigen, to treat or prevent the same infection in others began in the late 1880s when French and German scientists uncovered, one step at a time, several of the elements of the immune system's response to infection. A key finding was that the damage caused by some bacteria depends upon their secreted toxins which can be neutralized by biologic agents. Antitoxins to diphtheria and tetanus began to be manufactured in large animals in France, Germany, and the US in the 1890s and were soon being used worldwide. The impact of diphtheria antitoxin on childhood mortality was profound. Shortly after the development of antitoxins, convalescent serum began to be used for its anti-bactericidal properties thus addressing serious infections caused by non-toxin-producing organisms. The effectiveness of antitoxins and antisera was demonstrated by examining mortality rates in hospitals before and after the introduction of antitoxins, by comparisons of treated and untreated patients, by comparing early and late treatment and dosage, by examining vital data mortality trends, and by several randomized and alternate assignment trials. Antitoxins continue to have a role in the rare cases of diphtheria and other conditions largely eradicated by immunization, but serum therapy nearly disappeared from the medical armamentarium with the development of antibiotics in the 1940s. Inasmuch as new human pathogens are now emerging with unprecedented regularity as seen in the recent COVID-19 pandemic, and because specific therapies are unlikely to be available for them, plasma-based antibody therapies are likely to again carve out a niche in infectious disease control.

HemoClear: A Practical and Cost-Effective Alternative to Conventional Convalescent Plasma Retrieval Methods.

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.

The effect of convalescent plasma therapy on the rate of nucleic acid negative conversion in patients with persistent COVID-19 test positivity.

Objective: This study investigates the association between convalescent plasma therapy and the negative conversion rate in patients with persistent COVID-19 test positivity. Method: A retrospective analysis was conducted on patients with severe or mild to moderate COVID-19 whose viral nucleic acid tests remained positive for over 30 days. Patients were categorized into two groups: those who administered convalescent plasma therapy and those who were not. Data collected included information on therapy strategies used (convalescent plasma, corticosteroids, interferons, etc.), patients' demographic characteristics, comorbidities, therapeutic medications, and nucleic acid testing results. Patients in the convalescent plasma therapy group were matched 1:2 ratio with those in the non-convalescent plasma therapy group. Cumulative negative conversion rates on the fifth, tenth, and fifteenth days post-therapy initiation were analyzed as dependent variables. Independent variables included therapy strategies, demographic characteristics, comorbidities, and therapeutic medication usage. Univariate analysis was conducted, and factors with a p-value (P) less than 0.2 were included in a paired Cox proportional hazards model. Results: There was no statistically significant difference in the cumulative negative conversion rate between the convalescent plasma therapy group and the non-convalescent plasma therapy group on the fifth, tenth, and fifteenth days. Specifically, on day the fifth, the negative conversion rate was 41.46% in the convalescent plasma therapy group compared to 34.15% in the non-convalescent plasma therapy group (HR: 1.72, 95% CI: 0.82-3.61, P = 0.15). On the tenth day, it was 63.41% in the convalescent plasma therapy group and 63.41% in the non-convalescent plasma therapy group (HR: 1.25, 95% CI: 0.69∼2.26, P = 0.46). On the fifteenth day, the negative conversion rate was 85.37% in the convalescent plasma therapy group and 75.61% in the non-convalescent plasma therapy group (HR: 1.19, 95% CI: 0.71-1.97, P = 0.51). Conclusion: Our finding does not support the hypothesis that convalescent plasma therapy could accelerate the time to negative conversion in patients who consistently test positive for COVID-19.

Coexistence of low body mass index and poor oral health negatively affects activities of daily living, swallowing, and cognition after stroke.

AIM: Low body mass index (BMI) and poor oral health are prevalent among older stroke patients and associated with adverse outcomes. However, their combined impact on functional recovery after stroke remains unclear. This study investigated the synergistic effects of low BMI and poor oral health on activities of daily living (ADL) independence, swallowing function, and cognitive status in post-stroke older patients. METHODS: A retrospective cohort study was conducted on 708 hospitalized post-stroke patients aged ≥70 years. Low BMI was defined as <20 kg/m2, and poor oral health was assessed using the Revised Oral Assessment Guide (ROAG) with a score ≥13 indicating oral problems. The primary outcome was ADL independence (Functional Independence Measure-motor score >78) at discharge. Secondary outcomes included swallowing level (Food Intake Level Scale) and cognitive status (Functional Independence Measure-cognition score). Multiple regression analyses were performed to examine the associations of low BMI, poor oral health, and their combination with outcomes of interest. RESULTS: The coexistence of low BMI and poor oral health was independently associated with lower odds of achieving ADL independence (odds ratio 0.130, 95% confidence interval [CI] 0.023-0.718), worse swallowing level (B = -0.878, 95% CI -1.280 to -0.476), and poorer cognitive status (B = -1.872, 95% CI -2.960 to -0.784) at discharge, after adjusting for confounders. The combined impact was stronger than either condition alone. CONCLUSIONS: The coexistence of low BMI and poor oral health exerts a synergistic negative impact on functional recovery in older stroke inpatients. Comprehensive interventions integrating nutritional support, oral management, and rehabilitation are crucial to optimizing outcomes in this vulnerable population. Geriatr Gerontol Int 2024; 00: 000-000. Geriatr Gerontol Int 2024; ••: ••-••.

Impaired oral health associations with cognitive and motor decline in activities of daily living independence during hospitalization: insights from a post-stroke cohort.

PURPOSE: Evidence is scarce on the associations between impaired oral health and cognitive level related to independence in activities of daily living (ADLs) among hospitalized older patients. We aimed to evaluate the associations between baseline oral problems and changes in cognitive level in post-stroke patients. METHODS: A retrospective cohort study was conducted, encompassing consecutively hospitalized post-stroke patients. Revised Oral Assessment Guide (ROAG) as a measure of oral health and function was assessed at admission. Primary outcomes included discharge scores for cognitive function assessed by the cognitive domain of the Functional Independence Measure (FIM-cognition) and the corresponding change in FIM-cognition during hospitalization. Another outcome measure was the motor domain of FIM (FIM-motor). Multivariate linear regression analyses were employed to assess the association between baseline ROAG and the designated outcomes, adjusting for potential confounding factors. RESULTS: Data from 955 patients (mean age 73.2 years; 53.6% men) were included in the analysis. The median ROAG was 10 [9, 12], with 811 patients (84.9%) presenting oral problems. After fully adjusting for confounding factors, the ROAG was significantly and negatively associated with FIM-cognition at discharge (ß = -0.107, p = 0.031) and FIM-cognition gain (ß = -0.093, p = 0.018). Further, the ROAG was independently and negatively associated with FIM-motor at discharge (ß = -0.043, p = 0.013) and FIM-motor gain (ß = -0.065, p = 0.013). CONCLUSION: Oral problems were associated with compromised cognitive levels and a decline in physical function during the hospitalization in post-stroke patients. These results underscore the critical importance of addressing oral health in this patient population.

Impact of Hospital Dentistry on Patients' Food Intake Status in Convalescent Rehabilitation Ward.

BACKGROUND: Treating oral problems with dentist intervention during hospitalisation may improve patients' food intake status. OBJECTIVES: This study aimed to clarify whether convalescent rehabilitation ward inpatients in a hospital with hospital dentistry (HHD) had a better diet at discharge than those in a hospital without hospital dentistry (HNHD). METHODS: Retrospective observational study including inpatients with dental involvement in a HHD with dentists and dental hygienists and HNHD with dental hygienist and visiting dental service between 1 March and 31 August 2022. Data included age, sex, body mass index (BMI), Functional Independent Measure (FIM) motor and cognitive, Oral Health Assessment Tool (OHAT) score, Food Intake LEVEL Scale (FILS), whether the FILS ≥8 (indicating that patient eats also a non-texture-modified diet), remained and functional tooth numbers and speech language hearing therapist (SLHT) and dentist interventions. Comparisons between the two hospitals and factors that affected the FILS ≥8 were examined. RESULTS: A total of 333 and 89 inpatients were included in the HHD and HNHD groups, respectively. After propensity score matching, the HHD group had a significantly higher rate of FILS ≥8, functional tooth numbers at discharge, and SLHT and dentist intervention rates. The multivariable logistic regression analysis for propensity score matching participants showed that the significant independent variables for FILS ≥8 were age, BMI, FILS, FIM motor (all at admission) and SLHT and dentist interventions. Odds ratio for dentist intervention was 14.46 (95% CI: 4.36-48.01). CONCLUSIONS: Dentists are necessary to improve patients' food intake status in convalescent rehabilitation wards.

High-Throughput Screening Assay for Convalescent Sera in COVID-19: Efficacy, Donor Selection, and Variant Neutralization.

Convalescent sera, rich in pathogen-specific antibodies, offers passive immunity to patients with infectious diseases. Screening assays using convalescent sera are crucial for evaluating therapeutic efficacy, selecting suitable serum donors, and standardizing assays. They measure antibody levels, neutralizing potential, and specificity against viruses like SARS-CoV-2, ensuring therapeutic serum contains potent antibodies. Standardized procedures enable reliable results and wider adoption of serum therapy for COVID-19. We have developed a high-content image-based assay for screening convalescent sera against SARS-CoV-2 variants. Using various cell lines, we identified optimal candidates, employed immunofluorescence to visualize infected cells, and assessed neutralizing antibody efficacy. Screening convalescent sera for therapeutic potential identified neutralizing activity against SARS-CoV-2 variants. Dose-response analysis showed variable neutralizing activity, with some sera exhibiting broad neutralization. Additionally, we explored the synergy between neutralizing sera and ß-d-N4-hydroxycytidine (NHC), an initial metabolite of molnupiravir. These assays enhance serum therapy's benefits for COVID-19 treatment and aid in understanding neutralizing activity against SARS-CoV-2 variants, addressing viral challenges.

Triad of rehabilitation, nutrition support, and oral management improves activities of daily living and muscle health in hospitalized patients after stroke.

BACKGROUND AND AIMS: The triad approach combining rehabilitation, nutrition support, and oral management has garnered increasing interest for improving outcomes in older adults. However, evidence is limited regarding its effectiveness in post-stroke patients, who are at high risk for malnutrition, sarcopenia, oral problems, and dysphagia. This study aims to investigate the association between the triad approach and improvement in activities of daily living (ADL), muscle strength, and skeletal muscle mass in these patients. METHODS: A retrospective cohort study was conducted using post-stroke patients. Patients were divided into groups based on their exposure to the triad approach, defined as a combination of intensive chair-stand exercise (rehabilitation), personalized food prescriptions (nutrition support), and oral management by dental professionals. We investigated the association between the triad approach and outcomes using multiple linear regression analysis adjusted for covariates. Primary outcome was Functional Independence Measure motor score (FIM-motor) at discharge and its gain. Secondary outcomes were handgrip strength (HGS) and skeletal muscle mass index (SMI) at discharge. RESULTS: The study included 1012 post-stroke patients (median age 75.6 years; 54.1% men). Multiple linear regression analysis revealed that the triad approach had the strongest association with higher FIM-motor at discharge (ß = 0.262, p < 0.001) and FIM-motor gain (ß = 0.272, p < 0.001) compared to the individual or combined interventions. The triad also showed the strongest associations with higher HGS (ß = 0.090, p = 0.017) and SMI (ß = 0.041, p = 0.028) at discharge. CONCLUSIONS: The triad approach of intensive rehabilitation, personalized nutrition support, and oral management by dental professionals is strongly associated with improved ADL, muscle strength, and skeletal muscle mass in post-stroke rehabilitation patients. Implementing this multidisciplinary strategy may maximize functional and muscle health recovery.

Evidence for the Efficacy of COVID-19 Convalescent Plasma.

During the global health emergency caused by the coronavirus disease 2019 (COVID-19), evidence relating to the efficacy of convalescent plasma therapy-evidence critically needed for both public policy and clinical practice-came from multiple levels of the epistemic hierarchy. The challenges of conducting clinical research during a pandemic, combined with the biological complexities of convalescent plasma treatment, required the use of observational data to fully assess the impact of convalescent plasma therapy on COVID symptomatology, hospitalization rates, and mortality rates. Observational studies showing the mortality benefits of convalescent plasma emerged early during the COVID-19 pandemic from multiple continents and were substantiated by real-time pragmatic meta-analyses. Although many randomized clinical trials (RCTs) were initiated at the onset of the pandemic and were designed to provide high-quality evidence, the relative inflexibility in the design of clinical trials meant that findings generally lagged behind other forms of emerging information and ultimately provided inconsistent results on the efficacy of COVID-19 convalescent plasma. In the pandemic framework, it is necessary to emphasize more flexible analytic strategies in clinical trials, including secondary, subgroup, and exploratory analyses. We conclude that in totality, observational studies and clinical trials taken together provide strong evidence of a mortality benefit conferred by COVID-19 convalescent plasma, while acknowledging that some randomized clinical trials examined suboptimal uses of convalescent plasma.

The Importance of Geographic Proximity of Convalescent Plasma Donors.

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.

Generating the Evidence Base for Convalescent Plasma Use for a New Infectious Disease.

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.

Convalescent Plasma for Immunocompromised Patients.

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.

Convalescent Plasma and Other Antibody Therapies for Infectious Diseases-Lessons Learned from COVID-19 and Future Prospects.

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.

Relationship between Improvement in Physical Activity and Three Nutritional Assessment Indicators in Patients Admitted to a Convalescent Rehabilitation Ward.

We investigated the relationship between three nutritional indicators, the Mini Nutritional Assessment-Short Form (MNA-SF), Geriatric Nutritional Risk Index (GNRI), and Controlling Nutrition Status (CONUT), and physical activity at discharge in patients admitted to convalescent rehabilitation wards. The study included 1601 patients (77 ± 12 years, male 46.2%) discharged from convalescent rehabilitation wards between April 2018 and September 2023. MNA-SF, GNRI, and CONUT scores were obtained on admission. Patients were divided into two groups according to their level of Functional Independence Measure (FIM) walk score at discharge. The walking group (n = 1181, FIM walk score ≥ 5, 76 ± 13 years, male 47.2%) was significantly younger than the wheelchair group (n = 420, 79 ± 12 years, FIM walk score < 5, male 43.8%) and had significantly higher MNA-SF (6.5 ± 2.5 vs. 4.7 ± 2.4) and GNRI (93.1 ± 12.4 vs. 86.7 ± 10.9) scores and significantly lower CONUT (3.1 ± 2.3 vs. 3.9 ± 2.3) scores than the wheelchair group (all p < 0.01). Multivariate logistic regression analysis showed that age, handgrip strength, Functional Oral Intake Scale, and MNA-SF score were independently associated with walking ability at discharge (all p < 0.01). In addition, MNA-SF scores were independently associated with Rehabilitation Effectiveness. These results suggest that nutritional status, particularly MNA-SF scores on admission, is associated with improvement of physical activity at discharge.

Convalescent plasma and predictors of mortality among hospitalized patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Plasma collected from recovered patients with COVID-19 (COVID-19 convalescent plasma [CCP]) was the first antibody-based therapy employed to fight the COVID-19 pandemic. While the therapeutic effect of early administration of CCP in COVID-19 outpatients has been recognized, conflicting data exist regarding the efficacy of CCP administration in hospitalized patients. OBJECTIVES: To examine the effect of CCP compared to placebo or standard treatment, and to evaluate whether time from onset of symptoms to treatment initiation influenced the effect. DATA SOURCES: Electronic databases were searched for studies published from January 2020 to January 2024. STUDY ELIGIBILITY CRITERIA: Randomized clinical trials (RCTs) investigating the effect of CCP on COVID-19 mortality in hospitalized patients with COVID-19. PARTICIPANTS: Hospitalized patients with COVID-19. INTERVENTIONS: CCP versus no CCP. ASSESSMENT OF RISK OF BIAS: Cochrane risk of bias tool for RCTs. METHODS OF DATA SYNTHESIS: The random-effects model was used to calculate the pooled risk ratio (RR) with 95% CI for the pooled effect estimates of CCP treatment. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the certainty of evidence. RESULTS: Twenty-seven RCTs were included, representing 18,877 hospitalized patients with COVID-19. When transfused within 7 days from symptom onset, CCP significantly reduced the risk of death compared to standard therapy or placebo (RR, 0.76; 95% CI, 0.61-0.95), while later CCP administration was not associated with a mortality benefit (RR, 0.98; 95% CI, 0.90-1.06). The certainty of the evidence was graded as moderate. Meta-regression analysis demonstrated increasing mortality effects for longer interval to transfusion or worse initial clinical severity. CONCLUSIONS: In-hospital transfusion of CCP within 7 days from symptom onset conferred a mortality benefit.

Hemoglobin levels and cognitive trajectory: unveiling prognostic insights in post-stroke geriatric cohort.

PURPOSE: Evidence is scarce regarding the association between anemia and alterations in cognitive level among hospitalized older patients. We aimed to evaluate the associations between baseline hemoglobin (Hb) levels and changes in cognitive level in patients undergoing rehabilitation after stroke. METHODS: A retrospective cohort study was conducted, encompassing consecutively hospitalized post-stroke patients. Data on serum Hb levels were extracted from medical records, specifically tests conducted within 24 hours of admission. Primary outcomes included discharge scores for cognitive function assessed by the cognitive domain of the Functional Independence Measure (FIM-cognition) and the corresponding change in FIM-cognition during hospitalization. Another outcome measure was the length of hospital stay. Multivariate linear regression analyses were employed to assess the association between Hb levels at admission and the designated outcomes, adjusting for potential confounding factors. RESULTS: Data from 955 patients (mean age 73.2 years; 53.6% men) were included in the analysis. The median Hb level at admission was 13.3 [11.9, 14.5] g/dL. After fully adjusting for confounding factors, the baseline Hb level was significantly and positively associated with FIM-cognition at discharge (ß = 0.045, p = 0.025) and its gain (ß = 0.073, p = 0.025). Further, the baseline Hb level was independently and negatively associated with length of hospital stay (ß = -0.013, p = 0.026). CONCLUSION: Elevated baseline Hb levels are correlated with preserved cognitive level and shorter hospital stays in post-stroke patients. Evaluating anemia at the outset serves as a crucial prognostic indicator.

Convalescent Plasma as Adjunctive Therapy for Hospitalized Patients with COVID-19: The Co-CLARITY Trial.

Background and Objective: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients. Methods: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections. Results: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days. Conclusions: Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.

Sarcopenia and its components suppress the improvement of depression symptoms in patients with stroke.

Background: Recent studies have reported an association between sarcopenia and depression symptoms. To date, no reports have investigated the association between sarcopenia and depression symptoms evaluated using the Geriatric Depression Screening Scale (GDS)-15 in patients with stroke. Therefore, this study aimed to investigate the association between sarcopenia and its components and the improvement of depression symptoms in patients with stroke admitted to a convalescent rehabilitation ward. Methods: Patients with stroke aged ≥65 years admitted to a convalescent rehabilitation ward were included in the study. Participants were categorized into sarcopenia and non-sarcopenia groups based on the 2019 Asian Working Group for Sarcopenia. Here, depression symptoms were evaluated using the GDS-15, in addition to demographic characteristics. This study's primary outcome was the GDS change from admission to discharge. Multiple regression analysis was performed to investigate the association between GDS change and sarcopenia and its components. Results: Overall, 118 participants were included, with a mean age of 78.7±8.1, and 58 (49%) were classified in the sarcopenia group. Multiple regression analysis showed that sarcopenia (ß: -0.283, 95% confidence interval [CI]: -1.140 to -0.283, p < 0.001) and handgrip strength (ß: -0.317, 95% CI: -0.162 to -0.014, p = 0.021) were independently associated with GDS change. Conclusion: Sarcopenia and handgrip strength were significantly associated with improved depression symptoms in patients with stroke admitted to a convalescent rehabilitation ward. However, further prospective studies should investigate the association between sarcopenia and depression symptoms in patients with stroke.

Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update.

The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.

Anti-HNA testing of allo-exposed COVID-19 convalescent plasma donors including genetic human neutrophil antigen screening to prevent anti-HNA antibody-mediated transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury caused by antibodies against human neutrophil antigens (HNA) is a serious but rare complication associated with blood transfusion. The presence of such antibodies is most probable in donors with a transfusion/pregnancy history. During the COVID-19 pandemic period convalescent plasma (CP) containing neutralizing antibodies against SARS-CoV-2 was widely used for COVID-19 patients as a therapy in the absence of any treatment. The aim of the study was to work out a simple diagnostic algorithm of anti-HNA testing of allo-exposed CP donors including genetic HNA screening. MATERIALS AND METHODS: A total of 457 anti-HLA-negative allo-exposed CP donors were genotyped for HNA-1a/1b, HNA-3a/3b, and HNA-2, and only donors with homozygous HNA-1a/1a; HNA-3b/3b; or HNA-2null genotypes were tested for anti-HNA antibody using LabScreenMulti (One Lambda) and homozygous HNA-1b/1b using the granulocyte immunofluorescence test (GIFT) but verified using LabScreenMulti. RESULTS: Testing of 83 homozygous HNA-3b/3b; HNA-2null; or HNA-1a/1a donors revealed anti-HNA-3a antibody in one case. Testing of 181 HNA-1b/1b donors using GIFT gave 10 ambiguous results verified using LabScreenMulti which confirmed anti-HNA-1a antibody in one case. The frequency of FCGR3B*01 and *04 encoding HNA-1a was 0.34; FCGR3B*02, *03, and *05 encoding HNA-1b-0.66; SLC44A2*01 encoding HNA-3a-0.80; and SLC44A2*02 encoding HNA-3b-0.20. In 3.7% cases the HNA-2null genotype was revealed. DISCUSSION: Due to applying HNA genotyping as a primary test before anti-HNA antibody testing the serological work was limited only to HNA-homozygous donors revealing two anti-HNA immunized donors. The distribution of HNA genotypes in the cohort was similar to other Caucasian populations.