Search Results (156)

Our study demonstrates that IVIG lots manufactured in 2023–2024 contain neutralizing antibodies against circulating Omicron variants, including KP.3 and XEC. These variants are resistant to all convalescent plasma and IVIG preparations produced prior to 2023. Therefore, recent IVIG lots may provide some protection against COVID-19 caused by circulating SARS-CoV-2 variants. Full article

Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, long COVID (LC) has become a significant global health burden. While knowledge about LC is accumulating, studies on its prevention are still lacking. Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to investigate prevention options for LC. We identified fifteen articles on vaccines, seven on antivirals, and six on other interventions after searching for articles in the PubMed/MEDLINE database using the MeSH terms. Results: Most vaccine-related studies demonstrated a protective effect of COVID-19 vaccines against developing LC. Our review found an equivocal effect of antivirals, while metformin had a protective effect in outpatients and corticosteroids were protective in hospitalized patients against LC. Conversely, COVID-19 convalescent plasma and multiple micronutrient supplement did not confer any protection against LC. Conclusions: COVID-19 vaccination is vital as it not only prevents COVID-19 but also reduces the severity of illness and may help prevent LC. Further studies are warranted to shed light on preventive strategies for long COVID. Full article

Background/Objectives: Mortality from COVID-19 in intensive care units (ICUs) was not clearly reported in many regions during the first wave. We aimed to assess the characteristics and outcomes of ICU patients with COVID-19 in Saudi Arabia. Methods: This was a secondary data analysis of the Convalescent Plasma Trial. All patients who were recruited from King Fahad Hospital of the University (KFHU) in the Eastern Region of Saudi Arabia between 13 March 2020 and 13 September 2020 were included. Characteristics and outcomes, differences in characteristics and outcomes between Saudi and non-Saudi populations, and predictors of mortality were assessed. Results: The KFHU recruited 185 ICU patients with COVID-19. Of those, 90 (48.6%) were Saudi, and 95 (51.4%) were non-Saudi. The overall mean age was 56.7 years, and 71.9% were males. Compared with Saudis, non-Saudis were younger, with a mean age of 54.4 years, were more likely to be males (81.1%), and had a higher median respiratory rate (28.0 breaths/min vs. 24.0), a lower percentage of blood-oxygen saturation (86.0% vs. 91.0%), and higher median levels of ferritin per µg/L (820 vs. 550). The overall mortality rate was 33.0% (n = 61). The mortality rate in non-Saudis (42.1%) was higher than that in Saudis (23.3%). The variables associated with increased mortality included non-Saudi status (odds ratio [OR] 2.66; 95% CI: 1.05, 6.72), ferritin (OR 1.01; 95% CI: 1.00, 1.02), and intubation (OR 8.55; 95% CI: 2.92, 24.97). Conclusions: Since the mortality rate in non-Saudis was greater than that in Saudis, more efforts should be made to improve social determinants of health across non-Saudis in our region. Full article

Blood products, including apheresis platelets and plasma, are essential for medical use but pose risks of bacterial contamination and viral transmission. Platelets are prone to bacterial growth due to their storage conditions, while plasma requires extensive screening. This study explores rapid irradiation as an innovative pathogen reduction method. A clinical linear accelerator was configured to deliver ultra-high dose rate (6 kGy/min) irradiation to platelet and plasma components. Platelets spiked with Escherichia coli (E. coli; 10⁵ colony-forming units) were irradiated at 0.1–20 kGy, followed by bacterial growth and platelet count analysis. COVID-19 convalescent plasma (CCP) was irradiated at 25 kGy, and receptor-binding domain (RBD)-specific immunoglobulins (Ig) were assessed. Irradiation at 1 kGy reduced E. coli growth by 2.7-log without significant platelet loss, while 5 kGy achieved complete suppression. The estimated 6-log bacterial reduction dose (2.3 kGy) led to a 31% platelet count drop. Administering a 25 kGy virus-sterilizing dose to CCP resulted in a 9.2% decrease in RBD-specific IgG binding. This study demonstrates the proof-of-concept for rapid blood sterilization using a clinical linear accelerator. The method maintains platelet counts and CCP antibody binding at sterilizing doses, highlighting its potential as a point-of-care blood product sterilization solution. Full article

Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks. Unveiling the genomic intricacies of SARS-CoV-2 variants, including the WHO-designated Omicron variant, we explore diverse antiviral categories such as fusion inhibitors, protease inhibitors, transcription inhibitors, neuraminidase inhibitors, nucleoside reverse transcriptase, and non-antiviral interventions like importin α/β1-mediated nuclear import inhibitors, neutralizing antibodies, and convalescent plasma. Notably, Molnupiravir emerges as a pivotal player, now licensed in the UK. This review offers a fresh perspective on the historical evolution of COVID-19 therapeutics, from repurposing endeavors to the latest developments in oral anti-SARS-CoV-2 treatments, ushering in a new era of hope in the battle against the pandemic. Full article

Italy was the first western country to be hit by the COVID-19 pandemic and has suffered nearly 200,000 deaths so far during the four years of the pandemic. In March 2020, Italy first deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Despite this initial effort, the proportion of COVID-19 patients treated with CCP during the first two years of the pandemic (2020–2021) was very low (approximately 2% of individuals hospitalized for COVID-19). In this study, we estimated the number of actual inpatient lives saved by CCP treatment in Italy using national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimated the potential number of lives saved if CCP had been deployed to 100% of hospitalized patients or used in 15% to 75% of outpatients. According to these models, CCP usage in 2020–2021 saved between 385–1304 lives, but this number would have increased to 17,751–60,079 if 100% of inpatients had been transfused with CCP. Similarly, broader (15–75%) usage in outpatients could have prevented 21,187–190,689 hospitalizations (desaturating hospitals) and 6144–81,926 deaths. These data have important implications for convalescent plasma use in future infectious disease emergencies. Full article

Objective: This study aimed to assess changes in the morphology of the retina and cornea in patients treated and hospitalized during the acute active phase of SARS-CoV-2 infection. Methods: A total of 24 patients with symptomatic early COVID-19 disease and 38 healthy participants from a control group were enrolled in our study. Among them, 20 received oxygen therapy at flow rates ranging from 1–10 L, while four received high-flow intranasal oxygen therapy (HFNOT). Some patients were treated with other types of therapy, such as Remdesivir, COVID-19 convalescent plasma therapy, or Tocilizumab. In the study, we focused on the analysis of optical coherence tomography (OCT) images of the cornea and retina including corneal thickness, central retinal thickness, retinal nerve fiber layer (RNFL), and optic disc parameters. The measurements were acquired using Spectral-domain OCT REVO FC 130. Results: The analysis did not show significant changes between the examined ophthalmological parameters before and after therapy. Furthermore, there were no detected significant differences between the tested parameters of the retina and cornea in COVID-19-positive patients compared to the control group. Conclusions: No ophthalmological manifestations of COVID-19 disease were observed during the study. Taking into account the results of other publications, the lack of an unambiguous position on this topic requires further research. Full article

SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient—who did mount a SARS-CoV-2 IgM response—showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population. Full article

Background: Data show that due to endothelial damage and thrombogenic effects, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may accelerate the development of atherosclerosis and increase the risk of cardiovascular diseases (CVDs). The impaired metabolism of aminothiols increases oxidative stress, as these molecules are involved in antioxidant defense as well as in thiol redox control. In this study, total levels of selected aminothiols (i.e., cysteine (Cys), homocysteine (HCy), and glutathione) in convalescents after coronavirus disease of 2019 (COVID-19) were evaluated. The analyses were made according to the sex of the patients, time from COVID-19 onset, and COVID-19 severity. Methods: The study group consisted of 212 patients after COVID-19. Levels of total aminothiols were assessed in the blood plasma using high-performance liquid chromatography (HPLC). Results: The mean Cys concentrations were higher in men than in women (229.92 µmol/L ± 51.54 vs. 210.35 µmol/L ± 41.90, respectively; p = 0.003). Differences in Cys levels were also noticed in the total study group between patients distinguished due to time from disease onset (226.82 µmol/L ± 40.57 in <12 weeks, 232.23 µmol/L ± 47.99 in patients 12–24 weeks, and 208.08 µmol/L ± 48.43 in patients >24 weeks; p = 0.005). In addition, over 11% of total patients 12–24 weeks from disease onset had Cys levels above 300 µmol/L compared to almost 4% of patients <12 weeks and 2% of patients >24 weeks (p = 0.046). In sex-adjusted subgroups, significant differences due to time from COVID-19 were found in Cys levels in women (p = 0.004) and in glutathione levels in men (p = 0.024). None of the aminothiol levels differed between the subgroups based on the severity of COVID-19. Conclusions: Men had overall higher Cys levels than women. Cys levels were lower >24 weeks after COVID-19 onset than in the earlier period after disease onset. A partial elevation in Cys levels 12–24 weeks after the disease onset may contribute to the increase in CVD risk in the post-COVID-19 period. Full article

Background: Sample size estimation is an essential step in the design of randomized controlled trials (RCTs) evaluating a treatment effect. Sample size is a critical variable in determining statistical significance and, thus, it significantly influences RCTs’ success or failure. During the COVID-19 pandemic, many RCTs tested the efficacy of COVID-19 convalescent plasma (CCP) in hospitalized patients but reported different efficacies, which could be attributed to, in addition to timing and dose, inadequate sample size estimates. Methods: To assess the sample size estimation in RCTs evaluating the effect of treatment with CCP in hospitalized COVID-19 patients, we searched the medical literature between January 2020 and March 2024 through PubMed and other electronic databases, extracting information on expected size effect, statistical power, significance level, and measured efficacy. Results: A total of 32 RCTs were identified. While power and significance level were highly consistent, heterogeneity in the expected size effect was relevant. Approximately one third of the RCTs did not reach the planned sample size for various reasons, with the most important one being slow patient recruitment during the pandemic’s peaks. RCTs with a primary outcome in favor of CCP treatment had a significant lower median absolute difference in the expected size effect than unfavorable RCTs (20.0% versus 33.9%, P = 0.04). Conclusions: The analyses of sample sizes in RCTs of CCP treatment in hospitalized COVID-19 patients reveal that many underestimated the number of participants needed because of excessively high expectations on efficacy, and thus, these studies had low statistical power. This, in combination with a lower-than-planned recruitment of cases and controls, could have further negatively influenced the primary outcomes of the RCTs. Full article

Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma antibodies from COVID-19 convalescents. These antibodies were found to hydrolyze the S-protein and corresponding oligopeptides. Our study shows that for antibodies with affinity to recombinant structural proteins of the SARS-CoV-2: S-protein, its fragment RBD and N-protein can only hydrolyze the corresponding protein substrates and are not cross-reactive. By using strict criteria, we have confirmed that this proteolytic activity is an intrinsic property of antibodies and is not caused by impurities co-eluting with them. This discovery suggests that natural proteolytic antibodies that hydrolyze proteins of the SARS-CoV-2 virus may have a positive impact on disease pathogenesis. It is also possible for these antibodies to work in combination with other antibodies that bind specific epitopes to enhance the process of virus neutralization. Full article

This research explores the association between ABO blood groups and susceptibility to SARS-CoV-2 infection, analyzing Convalescent COVID-19 plasma (CCP) donors (n = 500) and healthy whole blood donors (BDs) (n = 9678) during the pandemic (1 May 2020 to 30 April 2021). A comparison is made with pre-pandemic BDs (n = 11,892) from 1 May 2018 to 30 April 2019. Significant differences in blood group distribution are observed, with blood group A individuals being three times more likely to be CCP donors. Conversely, blood groups B, O, and AB are less associated with CCP donation. Notably, blood group O is more prevalent among regular BDs, suggesting potential resistance to SARS-CoV-2 infection. This study underscores variations in blood group distribution during the pandemic compared to pre-pandemic periods. The findings support previous research indicating a link between blood group antigens and viral susceptibility, including SARS-CoV-2. Understanding these associations has implications for public health strategies, with potential for predicting COVID-19 outcomes and transmission patterns. Further research is crucial to explore molecular and immunological mechanisms, providing valuable insights for targeted preventive strategies and personalized healthcare in managing the impact of COVID-19. Full article

Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale. Full article

Demands for whole blood (WB) and COVID-19 convalescent plasma (CCP) donations during the SARS-CoV-2 (COVID-19) pandemic presented unprecedented challenges for blood services throughout the world. This study aims to understand the motivating factors that drive WB and CCP donations in the context of the pandemic. This cross-sectional study is based on data extracted from surveys of the two volunteer donor cohorts. The findings reveal that when compared to CCP donors, WB donors were more likely to view donation as a form of social engagement (97.7% vs. 87.1%, p < 0.01), advantageous in the workplace (46.4% vs. 28.6%, p < 0.01), advantageous in their social network (58.6% vs. 47.0%, p = 0.01), and view their donation in the context of positive self-satisfaction (99% vs. 95.1%, p = 0.01). The average age of CCP donors was 7.1 years younger than those who donated WB (p < 0.01). Motivational factors were also analyzed by sex and religiosity. In conclusion, whereas both donor groups showed a high motivation to partake in these life-saving commitments, WB donors were more likely to be motivated by factors that, when better-understood and implemented in policies concerning plasma donations, may help to increase these donations. Full article

Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated systematically. To assess the safety and efficacy of CCP combined with other agents for treatment of patients hospitalized for COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms was performed through PubMed, EMBASE, Cochrane central, medRxiv and bioRxiv. The main outcomes considered were mortality and safety of CCP combined with other treatments versus CCP alone. This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Measure of treatment effect was the risk ratio (RR) together with 95% confidence intervals (CIs). A total of 11 studies (8 randomized controlled trials [RCTs] and 3 observational) were included in the systematic review, 4 studies with CCP combined with remdesivir and 6 studies with CCP combined with corticosteroids, all involving hospitalized patients. One RCT reported information on both remdesivir and steroids use with CCP. The use of CCP combined with remdesivir was associated with a significantly reduced risk of death (RR 0.74; 95% CI 0.56–0.97; p = 0.03; moderate certainty of evidence), while the use of steroids with CCP did not modify the mortality risk (RR 0.72; 95% CI 0.34–1.51; p = 0.38; very low certainty of evidence). Not enough safety data were retrieved form the systematic literature analysis. The current evidence from the literature suggests a potential beneficial effect on mortality of combined CCP plus remdesivir compared to CCP alone in hospitalized COVID-19 patients. No significant clinical interaction was found between CCP and steroids. Full article