Approaching Pharmacological Space: Events and Components.

The pharmacological space comprises all the dynamic events that determine the bioactivity (and/or the metabolism and toxicity) of a given ligand. The pharmacological space accounts for the structural flexibility and property variability of the two interacting molecules as well as for the mutual adaptability characterizing their molecular recognition process. The dynamic behavior of all these events can be described by a set of possible states (e.g., conformations, binding modes, isomeric forms) that the simulated systems can assume. For each monitored state, a set of state-dependent ligand- and structure-based descriptors can be calculated. Instead of considering only the most probable state (as routinely done), the pharmacological space proposes to consider all the monitored states. For each state-dependent descriptor, the corresponding space can be evaluated by calculating various dynamic parameters such as mean and range values.The reviewed examples emphasize that the pharmacological space can find fruitful applications in structure-based virtual screening as well as in toxicity prediction. In detail, in all reported examples, the inclusion of the pharmacological space parameters enhances the resulting performances. Beneficial effects are obtained by combining both different binding modes to account for ligand mobility and different target structures to account for protein flexibility/adaptability.The proposed computational workflow that combines docking simulations and rescoring analyses to enrich the arsenal of docking-based descriptors revealed a general applicability regardless of the considered target and utilized docking engine. Finally, the EFO approach that generates consensus models by linearly combining various descriptors yielded highly performing models in all discussed virtual screening campaigns.

Feasibility and Effectiveness of Vaccines for COVID-19: An Umbrella Review.

Introduction: In January 2020, WHO declared the 2019 Coronavirus Disease (COVID-19) a pandemic. Though COVID-19 vaccines are recommended, ongoing surveillance is crucial due to potential unforeseen events. Evaluation of long-term effectiveness and safety and addressing emerging variants are vital. This study integrates systematic reviews to assess COVID-19 vaccine efficacy, immunogenicity, and safety comprehensively. Methods: This study was an umbrella review study on the feasibility and effectiveness of vaccines for COVID-19. We conducted a comprehensive search in PubMed, Web of Sciences, and Scopus, using MeSH terms and keywords related to COVID-19 vaccines. Inclusion criteria comprised peer-reviewed systematic reviews and meta-analyses in English, focusing on feasibility and effectiveness. Exclusion criteria targeted non-systematic reviews exclusively on vaccine safety and duplicates. Two independent reviewers screened and resolved discrepancies. Data extraction included key details. Methodological quality was assessed using the ROBIS tool. Data synthesis involves narrative and, if applicable, quantitative synthesis (meta-analysis). Reporting followed PRISMA guidelines. Results: A total of 32 systematic reviews were included in the study, of which 20 also conducted a meta-analysis. The studies investigated in the included reviews ranged from 7 to 74. The included articles were conducted in various countries around the globe. The findings indicated that COVID-19 vaccines are generally safe and effective for individuals with various medical conditions. The overall risk of bias for the included studies was assessed as low risk. Conclusion: The study outcomes indicated that mRNA vaccines exhibit a higher incidence of adverse events but demonstrate greater efficacy. Conversely, inactivated and protein subunit vaccines are safer but exhibit lower efficiency. Moreover, the vaccine is considered safe for individuals with specific conditions such as inflammatory bowel disease, solid organ transplant recipients, children, pregnant individuals, and those with hematologic problems. Ultimately, the acceptance of the COVID-19 vaccine among individuals is influenced by various factors, including geographic, socioeconomic, and pandemic-related considerations.

Choroiditis following severe acute respiratory syndrome coronavirus 2 infection in unvaccinated identical twins

ABSTRACT Unvaccinated identical twins developed bilateral anterior uveitis soon after the onset of coronavirus disease 2019 symptoms. During follow-up, both patients developed choroiditis, and one twine developed posterior scleritis and serous retinal detachment. Prompt treatment with oral prednisone ameliorated the lesions, and no recurrence was observed at the 18-month follow-up. Choroiditis may rarely be associated with severe acute respiratory syndrome coronavirus 2 infection, and it responds well to corticosteroid therapy. Although the exact mechanism is unknown, we hypothesize that the virus may act as an immunological trigger for choroiditis.

Convalescent anti-SARS-CoV-2 plasma for the treatment of patients with COVID-19: a retrospective study RESCOVID-19.

PURPOSE: Convalescent plasma (CP) collected from people who recovered from COVID-19 became a rapidly available treatment modality in numerous countries, including the Czech Republic. The aims of our study were to evaluate the effectiveness and safety of CP in the treatment of COVID-19. METHODS: This retrospective observational study involved six Czech hospitals. This study enrolled patients with and without CP treatment who were hospitalized between April 2020 and April 2021. Propensity score matching and logistic regression analysis were performed to evaluate the influence of CP administration and its timing on the in-hospital survival of COVID-19 patients. RESULTS: A total of 1,498 patients were enrolled in the study; 406 (27%) were administered CP, and 1,092 (73%) were not treated with CP. The propensity score-matched control group consisted of 1,218 subjects. The survival of patients treated with CP was 79%, while that of patients in the matched control group was 62% (P<0.001). Moreover, the chance of survival was significantly greater when CP was administered within three days after the onset of COVID-19 symptoms than when CP was administered after four or more days (87% vs. 76%, P <0.001). In addition, adverse effects related to CP administration were recorded in only 2% of patients and were considered mild in all patients. CONCLUSIONS: Our study demonstrated that the administration of CP was safe and possibly associated with positive effects that were more pronounced if CP was administered within the first three days after the onset of COVID-19 symptoms.

Impact of COVID-19 in pregnancy on maternal and perinatal outcomes during the Delta variant period: a comparison of the Delta and pre-delta time periods, 2020-2021.

BACKGROUND: To describe the impact on maternal and perinatal outcomes of the Delta variant of COVID-19 compared to the pre-Delta period in pregnant women with COVID-19 infections in one large public, non-profit hospital system. METHODS: We conducted a retrospective chart review of identified COVID-19 diagnosed pregnant women with the outcome of pregnancy (livebirth or stillbirths). We assessed maternal and perinatal outcomes between the pre-delta and Delta variant time periods. RESULTS: A study cohort of 173 mother-baby dyads was identified from January 2020 to November 2021. Maternal outcomes showed a higher rate of cesarean section (33.8%,49%; p = 0.047), with a higher frequency for worsening maternal condition due to COVID-19 (2.8%, 13.7%; p = 0.016) and association with non-reassuring fetal heart tones as indications for cesarean Sect. (53.8%, 95%; p = 0.008) during the Delta time period. There were more preterm births (16.9%, 32.4%; p = 0.023) even when excluding stillbirths (16.9%,30%; p = 0.05). Cesarean section due to "worsening maternal condition" was an independent risk factors for early delivery (ß = 2.66, 93.32-62.02, p < 0.001). The neonates had a longer mean (7.1 days, 9.9 days; p < 0.001) and median (2 days, 3 days; p < 0.001) length of stay during the Delta period. There was no difference in Apgar scores, NICU admissions or need for respiratory support between time periods. CONCLUSION: In a public, non-profit health system, from January 2020 to November of 2021, mothers with a diagnosis of COVID-19 during pregnancy, there were more preterm deliveries during the Delta time period, as well as longer length of stay for liveborn babies.

Strategies for developing self-assembled nanoparticle vaccines against SARS-CoV-2 infection.

In the recent history of the SARS-CoV-2 outbreak, vaccines have been a crucial public health tool, playing a significant role in effectively preventing infections. However, improving the efficacy while minimizing side effects remains a major challenge. In recent years, there has been growing interest in nanoparticle-based delivery systems aimed at improving antigen delivery efficiency and immunogenicity. Among these, self-assembled nanoparticles with varying sizes, shapes, and surface properties have garnered considerable attention. This paper reviews the latest advancements in the design and development of SARS-CoV-2 vaccines utilizing self-assembled materials, highlighting their advantages in delivering viral immunogens. In addition, we briefly discuss strategies for designing a broad-spectrum universal vaccine, which provides insights and ideas for dealing with possible future infectious sarbecoviruses.

Glycoprofile Comparison of the SARS-CoV-2 Spike Proteins Expressed in CHO and HEK Cell Lines.

Coronavirus SARS-CoV-2 spike protein remains a key focus of research due to a continued need for diagnostic and therapeutic tools to monitor and respond to new variants. Glycosylation of the spike protein is critical for the protein's functions in viral attachment and host cell entry. For scalable and cost-effective production of the spike protein, expression system-driven divergence in glycosylation patterns on recombinant spike proteins needs to be fully understood. This study assessed the N-glycosylation profiles of a full-length trimeric spike protein expressed in either Human Embryonic Kidney (HEK Expi293F) or Chinese Hamster Ovary (CHO-S) cells. Glycopeptide analysis was performed using a tandem mass spectrometry workflow and BioPharma Finder TM incorporating HEK and CHO glycan databases for protein characterisation. The results outline important differences in the variety and types of N-glycan generated by the two cell lines across the 22 known N-glycosylation sites of the spike protein. A notable increase in terminal sialylation, as well as the presence of the potentially immunogenic N-glycolylneuraminic acid at a functionally key N-glycosylation site, was observed in the CHO-S derived spike protein. With the potential for the relatively vast and more complex CHO glycan repertoire (182 glycans relative to 39 human glycans) to produce functional implications with CHO-S expressed spike protein, this study adds valuable knowledge to aid Quality by Design approaches and enable Multi Attribute Monitoring of specific N-glycosylation sites for proteoform analyses. This can further inform antigen development with future variants in order to devise updated diagnostic tests and therapeutic vaccine designs.

A Dual-Adjuvanted Parenteral-Intranasal Subunit Nanovaccine generates Robust Systemic and Mucosal Immunity Against SARS-CoV-2 in Mice.

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters can overcome the shortcomings of parenteral vaccines and enhance pre-existing systemic immunity. Here, a new protein subunit nanovaccine is developed by utilizing dual-adjuvanted (RIG-I: PUUC RNA and TLR-9: CpG DNA) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) along with SARS-CoV-2 S1 trimer protein, that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL subunit nanovaccine, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lungs and showed robust systemic humoral immunity. Interestingly, as a purely intranasal subunit vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. The data suggest that PUUC+CpG PAL subunit nanovaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

Associations Between Acute COVID-19 Symptom Profiles and Long COVID Prevalence: Population-Based Cross-Sectional Study.

Background: Growing evidence suggests that severe acute COVID-19 illness increases the risk of long COVID (also known as post-COVID-19 condition). However, few studies have examined associations between acute symptoms and long COVID onset. Objective: This study aimed to examine associations between acute COVID-19 symptom profiles and long COVID prevalence using a population-based sample. Methods: We used a dual mode (phone and web-based) population-based probability survey of adults with polymerase chain reaction-confirmed SARS-CoV-2 between June 2020 and May 2022 in the Michigan Disease Surveillance System to examine (1) how acute COVID-19 symptoms cluster together using latent class analysis, (2) sociodemographic and clinical predictors of symptom clusters using multinomial logistic regression accounting for classification uncertainties, and (3) associations between symptom clusters and long COVID prevalence using modified Poisson regression. Results: In our sample (n=4169), 15.9% (n=693) had long COVID, defined as new or worsening symptoms at least 90 days post SARS-CoV-2 infection. We identified 6 acute COVID-19 symptom clusters resulting from the latent class analysis, with flu-like symptoms (24.7%) and fever (23.6%) being the most prevalent in our sample, followed by nasal congestion (16.4%), multi-symptomatic (14.5%), predominance of fatigue (10.8%), and predominance of shortness of breath (10%) clusters. Long COVID prevalence was highest in the multi-symptomatic (39.7%) and predominance of shortness of breath (22.4%) clusters, followed by the flu-like symptom (15.8%), predominance of fatigue (14.5%), fever (6.4%), and nasal congestion (5.6%) clusters. After adjustment, females (vs males) had greater odds of membership in the multi-symptomatic, flu-like symptom, and predominance of fatigue clusters, while adults who were Hispanic or another race or ethnicity (vs non-Hispanic White) had greater odds of membership in the multi-symptomatic cluster. Compared with the nasal congestion cluster, the multi-symptomatic cluster had the highest prevalence of long COVID (adjusted prevalence ratio [aPR] 6.1, 95% CI 4.3-8.7), followed by the predominance of shortness of breath (aPR 3.7, 95% CI 2.5-5.5), flu-like symptom (aPR 2.8, 95% CI 1.9-4.0), and predominance of fatigue (aPR 2.2, 95% CI 1.5-3.3) clusters. Conclusions: Researchers and clinicians should consider acute COVID-19 symptom profiles when evaluating subsequent risk of long COVID, including potential mechanistic pathways in a research context, and proactively screen high-risk patients during the provision of clinical care.

Recent Advancements in the Delivery of Therapeutic Agents Targeting RNA-dependent RNA Polymerase of SARS-CoV-2.

This study aimed to undertake a complete evaluation and analysis of all known data on RNA-dependent RNA polymerase (RdRp) inhibitors, concentrating on their safety, efficacy, and current improvements in the delivery of therapeutic drugs targeting RdRp of SARS-CoV-2. The work has attempted to emphasise the necessity for future research into the development of nanocarrier-based targeted drug delivery methods for RdRp inhibitors in the treatment of COVID-19. In December 2019, a novel SARS-- CoV-2 strain was discovered in Wuhan, China. SARS-CoV-2 is transferable among humans and has caused a global pandemic. The rapid global outbreak of SARS-CoV-2 and numerous deaths caused because of coronavirus disease (COVID-19) prompted the World Health Organization to announce a pandemic on March 12, 2020. COVID-19 is becoming a key concern that has a significant impact on an individual's life status. RdRp inhibitors are major pharmaceutical agents used in the treatment of COVID-19, which have various undesirable side effects, a greater risk of recurrence, lower bioavailability, as well as a lack of targeted therapy. Hence, the present article has provided a review on all known data on RdRp inhibitors, safety, and efficacy, and recent advances in the delivery of therapeutic agents targeting RdRp of SARS-CoV-2. An analysis has been done using a scientific data search engine, such as the National Center for Biotechnology Information (NCBI/PubMed), Science Direct, Google Scholar, WIPO, Lens, etc. The information has emphasized the need for more research into the safety, efficacy, and development of nanocarrier-based targeted drug delivery systems for RdRp inhibitors in the treatment of COVID-19.

Metabolomic characterization of COVID-19 survivors in Jilin province.

BACKGROUND: The COVID-19 pandemic has escalated into a severe global public health crisis, with persistent sequelae observed in some patients post-discharge. However, metabolomic characterization of the reconvalescent remains unclear. METHODS: In this study, serum and urine samples from COVID-19 survivors (n = 16) and healthy subjects (n = 16) underwent testing via the non-targeted metabolomics approach using UPLC-MS/MS. Univariate and multivariate statistical analyses were conducted to delineate the separation between the two sample groups and identify differentially expressed metabolites. By integrating random forest and cluster analysis, potential biomarkers were screened, and the differential metabolites were subsequently subjected to KEGG pathway enrichment analysis. RESULTS: Significant differences were observed in the serum and urine metabolic profiles between the two groups. In serum samples, 1187 metabolites were detected, with 874 identified as significant (457 up-regulated, 417 down-regulated); in urine samples, 960 metabolites were detected, with 39 deemed significant (12 up-regulated, 27 down-regulated). Eight potential biomarkers were identified, with KEGG analysis revealing significant enrichment in several metabolic pathways, including arginine biosynthesis. CONCLUSIONS: This study offers an overview of the metabolic profiles in serum and urine of COVID-19 survivors, providing a reference for post-discharge monitoring and the prognosis of COVID-19 patients.

Macrolide resistance outcomes after the Covid-19 pandemic: A one health approach investigation.

During the Covid-19 pandemic period, the indiscriminate use of macrolide-class antibiotics was frequent among the Brazilian population due to the lack of knowledge and information with a scientific basis. Thus, the class of drugs that includes azithromycin, clarithromycin, and erythromycin, which alter metabolic reactions in the body and act on the immune system, was widely used without medical prescription. Samples of bacterial strains from hospital environments were obtained during the most extensive spread of Covid-19 and studied in the present article, emphasizing the investigation for macrolide resistance genes (erm and msr) bacteria of the genus Staphylococcus isolated from urinary tract infections. In addition, the physiological, genetic, immunological, and socio-epidemiological aspects were highlighted with a focus on the One Health approach and implications on the gut-brain axis in this integrative research, revealing that the inappropriate use of antibiotics directly affects entire communities, representing a significant concern for public and environmental health.

COVID-19 complicated with severe M1UK-lineage Streptococcus pyogenes infection in elderly patients: A report of two cases.

Case 1: A 71-year-old man was admitted to our hospital with progressive fever and dyspnea, which had developed three days after the onset of COVID-19. Initial chest computed tomography (CT) revealed a pulmonary lesion consistent with a secondary bacterial infection. Streptococcus pyogenes was isolated from cultures of primary sputum collected from the endotracheal tube, and identified as the causative microorganism. Case 2: A 91-year-old man was transferred to our hospital with severe hypotension, which had developed nine days after the onset of COVID-19. A chest CT revealed pericardial effusion and pericardiocentesis yielded purulent fluid. S. pyogenes was isolated from the fluid specimens and was identified as the causative microorganism of the secondary bacterial pericarditis. Isolates from both patients were subsequently identified as M1UK-lineage S. pyogenes via genetic analysis. This report implicates COVID-19 as a potential risk factor for severe M1UK infection via the respiratory tract.

COVID-19 vaccination anti-cancer impact on the PI3K/AKT signaling pathway in MC4L2 mice models.

The most promising method of containing the COVID-19 pandemic is considered to be vaccination against SARS-CoV-2 infection. However, research on the relationship between vaccination against COVID-19 and cancer has primarily examined induced immunity rather than the disease itself. Considering that breast cancer is the most common cancer among women, the main goal of this study was to examine the impact of the Sinopharm and AstraZeneca vaccination on tumor characteristics such as tumor size, important tumor markers, tumor-infiltrating lymphocytes, metastasis to vital organs, and investigation of the PI3K/AKT signaling pathway, and the expression levels of relevant genes (PTEN, mTOR, AKT, PI3K, GSK3, and FoxO1) of the luminal B (MC4L2) mouse model. The tumor size of the mice was measured and monitored every two days, and after thirty days, the mice were euthanized. Remarkably, after vaccination, all vaccinated mice showed a decrease in the size of their tumor and an increase in the number of lymphocytes that had invaded the tumors. Tumor marker levels (VEGF, Ki-67, MMP-2/9), CD4/CD8 ratio, metastasis to vital organs, hormone receptors (ER, PR, and HER-2), and expression of genes related to the advancement of the PI3K/AKT signaling pathway were lower in vaccinated mice. Our research showed that the COVID-19 vaccine can have an anti-cancer effect by slowing the tumor progression and metastasis.

Validation of monocyte CD169 expression as a valuable rapid diagnostic marker of SARS-CoV-2 and other acute viral infections.

OBJECTIVES: Acute infectious diseases are some of the most common reasons for receiving medical care, and analysis of the host immune response is an attractive approach for their diagnosis. The present study aimed to evaluate the potential usefulness of CD169 expression on peripheral monocytes (mCD169) as a marker of viral-associated host immune response. METHODS: In a large mono-institutional cohort of 4,025 patients evaluated for SARS-CoV-2 (CoV2) and other viral infections, mCD169 analysis was performed by rapid flow cytometry assay. RESULTS: Increased mCD169 values (median, 17.50; IQR, 8.40-25.72) were found in 1,631 patients with CoV2+ acute infection compared to 2,394 in CoV2- patients (median, 2.35; IQR, 2.0-3.25) (odds ratio [OR], 21.84; 95% CI ,17.53-27.21; P < .001). Among CoV2- patients, 1,484 (62.0%) were assessed for other viral infections, and viral etiology was laboratory confirmed in 428 patients (CoV2- Vir+), with RNA viruses most frequently detected (94.6%). Higher levels of mCD169 were also confirmed in CoV2- Vir+ compared to CoV2- Vir- patients (OR, 10.05; 95% CI, 7.35-13.74; P < .001). CONCLUSIONS: mCD169 analysis by rapid flow cytometry assay may be a sensitive broad marker useful for the rapid triage of patients with suspected acute viral infections and could potentially be directly applied to eventual new emergent viral outbreaks.

Detailed review of mortality reported following COVID-19 vaccination in Victoria, Australia: 2021-2023.

INTRODUCTION: The scale of the COVID-19 vaccine program, and appropriate focus on older individuals, emphasised monitoring of mortality as an important part of COVID-19 vaccine safety surveillance, noting many deaths temporally associated with vaccination may not be causally related. This cross-sectional study describes Victoria's vaccine safety service (SAEFVIC) process of reviewing mortality reports following COVID-19 vaccination, summarises report characteristics and identifies trends in mortality reporting. METHODS: Mortality cases reported to SAEFVIC following COVID-19 vaccination from 22 February 2021 to 22 February 2023 were included. Report characteristics, demographics, and cause of death information were described. Proportions of mortality reports per 100,000 vaccine doses administered were calculated, overall and stratified by age (<60 years, ≥60 years), sex, vaccine type and dose number. Rate ratios (RR) were used to compare proportions. RESULTS: Reporting proportions were higher in the first three months of the vaccine program (3.98 per 100,000 doses), compared to the following 21 months (0.71 per 100,000 doses), RR:5.61, p < 0.001. Of 159 mortality reports included, 135/159 (84.9 %) were in individuals ≥60 years. Most individuals (121/159, 90.3 %) had comorbidities relevant to cause(s) of death, and 143/159 (89.9 %) were categorised as having a 'likely alternate' cause of death based on treating clinician/forensic assessment. For 11/159 (6.9 %) reports vaccine contribution to death could not be determined. Five deaths (0.03 per 100,000 doses administered), all publicly reported, were assessed by the national regulator as likely vaccine-associated. CONCLUSIONS: Mortality reporting predominantly reflected the health status of the population receiving vaccines, vaccine administration patterns and contextual factors surrounding COVID-19 vaccines (including public concerns regarding serious adverse events of special interest), as well as extremely rare but fatal adverse events that were likely vaccine-associated. Jurisdictional vaccine safety services such as SAEFVIC play an important role in follow-up of mortality reports, supporting the work of national regulators, and thereby supporting vaccine safety surveillance and vaccine confidence more broadly.

Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity.

Existing antibodies (Abs) have varied effects on humoral immunity during subsequent infections. Here, we leveraged in vivo systems that allow precise control of antigen-specific Abs and B cells to examine the impact of Ab dose, affinity, and specificity in directing B cell activation and differentiation. Abs competing with the B cell receptor (BCR) epitope showed affinity-dependent suppression. By contrast, Abs targeting a complementary epitope, not overlapping with the BCR, shifted B cell differentiation toward Ab-secreting cells. Such Abs allowed for potent germinal center (GC) responses to otherwise poorly immunogenic sites by promoting antigen capture and presentation by low-affinity B cells. These mechanisms jointly diversified the B cell repertoire by facilitating the recruitment of high- and low-affinity B cells into Ab-secreting cell, GC, and memory B cell fates. Incorporation of small amounts of monoclonal Abs into protein- or mRNA-based vaccines enhanced immunogenicity and facilitated sustained immune responses, with implications for vaccine design and our understanding of protective immunity.

Transfusion safety concerns during the COVID-19 pandemic in Taiwan: Altered by evolving control strategies.

BACKGROUND: In 2022, the SARS-CoV-2 Omicron surge affected 8.8 million people in Taiwan. This study delves into how the transition from containment to mitigation strategies in COVID-19 control has altered concerns regarding transfusion safety. METHODS: Blood donations during 2020-2022 in Taiwan were included. Donation details and post-donation information (PDI) were retrieved to assess donation fluctuations and incidences of various PDI. The main effects of PDI reporting were assessed using chi-square test and logistic regression. Additionally, from April to August 2022, we collected disease information from COVID-19 donors, and tested their repository specimens for SARS-CoV-2 RNA and antibodies. RESULTS: Before 2022, when containment measures were in place, only 8 blood donors with COVID-19 reported PDI. However, by mid-2021, there was a significant decrease in blood donations. In 2022, with mitigation strategies implemented, a total of 3483 donations reported COVID-19 PDI. The incidence of all cause PDI increased from 10.5 per 10,000 donations in 2020-2021 to 29.9 per 10,000 in 2022, with nearly 70% of PDI being related to COVID-19. Female donors reported more PDI events. Additionally, the incidence significantly decreased with age. A total of 1148 repository specimens from COVID-19 donor were tested, revealing no detection of SARS-CoV-2 RNA. The seroprevalence rates of anti-nucleocapsid(N) and anti-spike(S) antibodies were 0.61% and 98.4%, respectively. CONCLUSION: Transfusion safety concerns in Taiwan progressed alongside the evolution of control strategies, with a one-year delay following the pandemic started. The absence of RNAemia among COVID-19 donors indicates that precautionary measures were commensurate with the risk.

Face masks and protection against COVID-19 and other viral respiratory infections: Assessment of benefits and harms in children.

Mask mandates for children were implemented at schools and childcare centers during the COVID-19 pandemic, and the US continues to recommend masking down to the age of two in certain settings. Medical interventions should be informed by high-quality evidence and consider the possibility of harm (i.e., include harm-benefit analyses). In this review, we weigh the existing evidence for the effectiveness of mask mandates to protect against COVID-19 and other viral respiratory infections and the harms associated with face mask wearing in children. There is a lack of robust evidence of benefit from masking children to reduce transmission of SARS-CoV-2 or other respiratory viruses. The highest quality evidence available for masking children for COVID-19 or other viral respiratory infections has failed to find a beneficial impact against transmission. Mechanistic studies showing reduced viral transmission from use of face masks and respirators have not translated to real world effectiveness. Identified harms of masking include negative effects on communication and components of speech and language, ability to learn and comprehend, emotional and trust development, physical discomfort, and reduction in time and intensity of exercise. Effectiveness of child masking has not been demonstrated, while documented harms of masking in children are diverse and non-negligible and should prompt careful reflection. Recommendations for masking children fail basic harm-benefit analyses.