Case report: Dysphagia after COVID-19 infection in a stroke patient-Is neurostimulation a potential management?

A 90-year-old man with stroke was weaned from tube feeding 4 months after stroke onset. However, he had a coronavirus disease 2019 (COVID-19) infection after 2 months and suffered from drastically worsened oropharyngeal dysphagia that required a reinsertion of the nasogastric tube. A videofluoroscopic swallowing study revealed poor bolus oral transit, significantly delayed swallowing reflex, reduced pharyngeal movements, and insufficient cough response. Repetitive transcranial magnetic stimulation and neuromuscular electrical stimulation were applied, in addition to conventional swallowing training. The feeding tube was removed after 20 treatment sessions. Clinicians should be aware of the risk of dysphagia after COVID-19 infection in patients with underlying neurological diseases. The management of post-COVID-19 dysphagia has not yet been fully established. Repetitive transcranial electrical stimulation combined with neuromuscular electrical stimulation may be used as an auxiliary intervention in specific cases.

Case report of new-onset ulcerative colitis after MVC-COVI1901 vaccine injection for SARS-CoV-2.

A 23-year-old man suffered from diarrhea after receiving the MVC-COVI1901 vaccine. The patient then presented to our emergency department due to swelling and pain in his right knee. Synovial effusion studies of the right knee revealed inflammation. Gram and acid-fast stains reported negative results and no crystals were found under a polarized light microscope. During his hospitalization, the patient underwent a colonoscopy and computed tomography (CT) due to bloody stool. Pancolitis was suspected under colonoscopy and an abdominal CT scan supported our diagnosis showing wall thickening and mucosal enhancement. Pathology showed distorted crypt architecture and acute cryptitis with abscesses. After excluding other causes of ulcerative colitis (UC), the patient was diagnosed with MVC-COV1901 vaccine-related UC and inflammatory bowel disease arthropathy. Subsequent presentation of UC and inflammatory bowel disease-related arthropathy after receiving the MVC-COVI1901 vaccine has not previously been reported. We speculate that the pathogenesis could be correlated to the vaccine's components (spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide) through the combination of 2 effects: the activation of Toll-like receptor (TLR) 4 by S-2P, and the activation of TLR9 and expression of interleukin-13 by CpG-1018 adjuvant. In conclusion, it is remarkable that the MVC-COVI1901 vaccine may lead to the incidence of autoinflammatory diseases such as UC.

Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Superrepellent Doubly Reentrant Geometry Promotes Antibiofouling and Prevention of Coronavirus Contamination.

The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID-19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID-19 pandemic.

Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.

Integrated Chinese herbal medicine and Western medicine successfully resolves spontaneous subcutaneous emphysema and pneumomediastinum in a patient with severe COVID-19 in Taiwan: A case report.

CASE: Serious complications of severe coronavirus disease 2019 (COVID-19) include subcutaneous emphysema (SE) and pneumomediastinum, which are complicated to treat with conventional Western medicine. We report how combining Chinese herbal medicine (CHM) with Western medicine quickly resolved a patient's COVID-19-associated pulmonary complications, shortened hospital stay and improved quality of life. CLINICAL FEATURES AND OUTCOME: A 59-year-old male with a history of smoking and tumors was diagnosed with COVID-19 in May 2021. At hospitalization, his oxygen saturation (SpO2) was 80%, he had a continuous severe cough, rapid shallow breathing, spontaneous SE and pneumomediastinum. By Day 4 of hospitalization, his condition was worsening despite standard care, so CHM was added. After 3-5 days, his coughing had lessened and supplementary oxygen therapy was de-escalated. Nine days after starting CHM, the SE had completely resolved and the patient avoided intubation. His WHO OS 10-point Scale score had fallen from 6 to 3 points and the modified Medical Research Council Dyspnea Scale score from 4 to 2 points. He was hospitalized for 19 days. At 1 week post-discharge, the patient could handle most of his daily activities and experienced minor shortness of breath only when performing labor-intensive tasks. At 1 month, his work output was restored to pre-COVID-19 levels. CONCLUSION: CHM combined with standard Western medicine improved pulmonary function, respiratory rate, blood oxygen saturation and shortened the hospital stay of a patient with severe COVID-19 complicated by SE and pneumomediastinum.

Neuro-ophthalmological Presentation of Optic Neuritis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare demyelinating autoimmune disorder of the central nervous system. MOGAD frequently manifests with severe, bilateral, and episodes of recurrent optic neuritis (ON) and is an important differential diagnosis to multiple sclerosis and aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorders. Besides ON, the clinical manifestations of MOGAD commonly include transverse myelitis, acute disseminated encephalomyelitis, and brain stem encephalitis. In this review, we summarize the current knowledge of the neuro-ophthalmological presentation of MOGAD-ON. We describe epidemiological aspects, including the association with COVID-19 and other infections or vaccinations, clinical presentation, and imaging findings of MOGAD-ON in the acute stage and during remission. Furthermore, we report findings on prognosis, treatment response, and changes in ON-unaffected eyes. We touch upon findings on visual acuity, visual fields, and visual evoked potentials, as well as structural changes assessed with optical coherence tomography. Moreover, we explain how to differentiate MOGAD from its differential diagnoses, including other neuroinflammatory disorders (multiple sclerosis and neuromyelitis optica spectrum disorders), but also idiopathic intracranial hypertension.

Association of malnutrition with SARS-CoV-2 vaccine response in patients undergoing hemodialysis.

BACKGROUND & AIMS: Patients undergoing dialysis are less likely to develop immune responses to SARS-CoV-2 vaccine. Malnutrition is common in the dialysis population. However, whether malnutrition contributes to the impaired immunogenicity remains unknown. The aim of this study was to assess the association between nutritional status and SARS-CoV-2 vaccine response in patients receiving maintenance hemodialysis. METHODS: A total of 206 hemodialysis patients (mean age, 67 ± 13 years) without prior SARS-CoV-2 infection were examined for the primary outcome of seroconversion, defined as the detection of IgG antibodies (≥50 AU/mL) to the receptor-binding domain of the S1 spike protein of SARS-CoV-2 one month after a priming dose of ChAdOx1 nCoV-19, an adenovirus-vectored vaccine. Nutritional status was assessed by using the Controlling Nutritional Status (CONUT) score, an objective indicator of nutrition incorporating serum albumin, total cholesterol, and total lymphocyte count, as well as the subjective global assessment (SGA). RESULTS: Overall, 16.5% of patients were classified as malnourished, and 64.1% of patients were at risk for malnutrition based on the CONUT score. Anti-SARS-CoV-2 IgG were the highest in patients with normal nutrition. In multivariate logistic regression analyses adjusted for age, sex, comorbidities, and use of immunosuppressants, patients with malnutrition remained less likely to develop an antibody response than those with normal nutrition (odds ratio 0.23, 95% CI, 0.07-0.76). SGA was a significant predictor of anti-SARS-CoV-2 IgG seroconversion in univariate but not multivariate analyses. CONCLUSIONS: Malnutrition according to CONUT score is associated with impaired humoral responses to SARS-CoV-2 vaccination in patients undergoing hemodialysis. Our results highlight the importance of incorporating nutritional assessment into routine dialysis care to identify patients at risk for suboptimal immune responses after SARS-CoV-2 vaccination. Further research is needed to determine whether nutritional intervention can improve immune responses in these vulnerable patients.

New Surveillance Metrics for Alerting Community-Acquired Outbreaks of Emerging SARS-CoV-2 Variants Using Imported Case Data: Bayesian Markov Chain Monte Carlo Approach.

BACKGROUND: Global transmission from imported cases to domestic cluster infections is often the origin of local community-acquired outbreaks when facing emerging SARS-CoV-2 variants. OBJECTIVE: We aimed to develop new surveillance metrics for alerting emerging community-acquired outbreaks arising from new strains by monitoring the risk of small domestic cluster infections originating from few imported cases of emerging variants. METHODS: We used Taiwanese COVID-19 weekly data on imported cases, domestic cluster infections, and community-acquired outbreaks. The study period included the D614G strain in February 2020, the Alpha and Delta variants of concern (VOCs) in 2021, and the Omicron BA.1 and BA.2 VOCs in April 2022. The number of cases arising from domestic cluster infection caused by imported cases (Dci/Imc) per week was used as the SARS-CoV-2 strain-dependent surveillance metric for alerting local community-acquired outbreaks. Its upper 95% credible interval was used as the alert threshold for guiding the rapid preparedness of containment measures, including nonpharmaceutical interventions (NPIs), testing, and vaccination. The 2 metrics were estimated by using the Bayesian Monte Carlo Markov Chain method underpinning the directed acyclic graphic diagram constructed by the extra-Poisson (random-effect) regression model. The proposed model was also used to assess the most likely week lag of imported cases prior to the current week of domestic cluster infections. RESULTS: A 1-week lag of imported cases prior to the current week of domestic cluster infections was considered optimal. Both metrics of Dci/Imc and the alert threshold varied with SARS-CoV-2 variants and available containment measures. The estimates were 9.54% and 12.59%, respectively, for D614G and increased to 14.14% and 25.10%, respectively, for the Alpha VOC when only NPIs and testing were available. The corresponding figures were 10.01% and 13.32% for the Delta VOC, but reduced to 4.29% and 5.19% for the Omicron VOC when NPIs, testing, and vaccination were available. The rapid preparedness of containment measures guided by the estimated metrics accounted for the lack of community-acquired outbreaks during the D614G period, the early Alpha VOC period, the Delta VOC period, and the Omicron VOC period between BA.1 and BA.2. In contrast, community-acquired outbreaks of the Alpha VOC in mid-May 2021, Omicron BA.1 VOC in January 2022, and Omicron BA.2 VOC from April 2022 onwards, were indicative of the failure to prepare containment measures guided by the alert threshold. CONCLUSIONS: We developed new surveillance metrics for estimating the risk of domestic cluster infections with increasing imported cases and its alert threshold for community-acquired infections varying with emerging SARS-CoV-2 strains and the availability of containment measures. The use of new surveillance metrics is important in the rapid preparedness of containment measures for averting large-scale community-acquired outbreaks arising from emerging imported SARS-CoV-2 variants.

Tag-Free SARS-CoV-2 Receptor Binding Domain (RBD), but Not C-Terminal Tagged SARS-CoV-2 RBD, Induces a Rapid and Potent Neutralizing Antibody Response.

Recombinant proteins are essential in the development of subunit vaccines. In the design of many recombinant proteins, polyhistidine residues are added to the N- or C-termini of target sequences to facilitate purification. However, whether the addition of tag residues influences the immunogenicity of proteins remains unknown. In this study, the tag-free SARS-CoV-2 RBD and His-tag SARS-CoV-2 RBD proteins were investigated to determine whether there were any differences in their receptor binding affinity and immunogenicity. The results showed that the tag-free RBD protein had a higher affinity for binding with hACE2 receptors than His-tag RBD proteins (EC50: 1.78 µM vs. 7.51 µM). On day 21 after primary immunization with the proteins, the serum ELISA titers of immunized mice were measured and found to be 1:1418 for those immunized with tag-free RBD and only 1:2.4 for His-tag RBD. Two weeks after the booster dose, tag-free-RBD-immunized mice demonstrated a significantly higher neutralizing titer of 1:369 compared with 1:7.9 for His-tag-RBD-immunized mice. Furthermore, neutralizing antibodies induced by tag-free RBD persisted for up to 5 months and demonstrated greater cross-neutralization of the SARS-CoV-2 Delta variant. Evidence from Western blotting showed that the serum of His-tag-RBD-immunized mice recognized irrelevant His-tag proteins. Collectively, we conclude that the addition of a polyhistidine tag on a recombinant protein, when used as a COVID-19 vaccine antigen, may significantly impair protein immunogenicity against SARS-CoV-2. Antibody responses induced were clearly more rapid and robust for the tag-free SARS-CoV-2 RBD than the His-tag SARS-CoV-2 RBD. These findings provide important information for the design of antigens used in the development of COVID-19 subunit vaccines.

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.

Association of malnutrition with SARS-CoV-2 vaccine response in patients undergoing hemodialysis

Background & aims Patients undergoing dialysis are less likely to develop immune responses to SARS-CoV-2 vaccine. Malnutrition is common in the dialysis population. However, whether malnutrition contributes to the impaired immunogenicity remains unknown. The aim of this study was to assess the association between nutritional status and SARS-CoV-2 vaccine response in patients receiving maintenance hemodialysis. Methods A total of 206 hemodialysis patients (mean age, 67±13 years) without prior SARS-CoV-2 infection were examined for the primary outcome of seroconversion, defined as the detection of IgG antibodies (≥50 AU/mL) to the receptor-binding domain of the S1 spike protein of SARS-CoV-2 one month after a priming dose of ChAdOx1 nCoV-19, an adenovirus-vectored vaccine. Nutritional status was assessed by using the Controlling Nutritional Status (CONUT) score, an objective indicator of nutrition incorporating serum albumin, total cholesterol, and total lymphocyte count, as well as the subjective global assessment (SGA). Results Overall, 16.5% of patients were classified as malnourished, and 64.1% of patients were at risk for malnutrition based on the CONUT score. Anti-SARS-CoV-2 IgG were the highest in patients with normal nutrition. In multivariate logistic regression analyses adjusted for age, sex, comorbidities, and use of immunosuppressants, patients with malnutrition remained less likely to develop an antibody response than those with normal nutrition (odds ratio 0.23, 95% CI, 0.07–0.76). SGA was a significant predictor of anti-SARS-CoV-2 IgG seroconversion in univariate but not multivariate analyses. Conclusions Malnutrition according to CONUT score is associated with impaired humoral responses to SARS-CoV-2 vaccination in patients undergoing hemodialysis. Our results highlight the importance of incorporating nutritional assessment into routine dialysis care to identify patients at risk for suboptimal immune responses after SARS-CoV-2 vaccination. Further research is needed to determine whether nutritional intervention can improve immune responses in these vulnerable patients.

Evaluating correlates of protection for mix-match vaccine against COVID-19 VOCs with potential of evading immunity.

BACKGROUND: In the face of rapid emerging variants of concern (VOCs) with potential of evading immunity from Beta to Omicron and uneven distribution of different vaccine brands, a mix-match strategy has been considered to enhance immunity. However, whether increasing immunogenicity using such a mix-match can lead to high clinical efficacy, particularly when facing Omicron pandemic, still remains elusive without using the traditional phase 3 trial. The aim of this study is to demonstrate how to evaluate correlates of protection (CoP) of the mix-match vaccination. METHODS: Data on neutralizing antibody (NtAb) titers and clinical efficacy against Wuhan or D614G strains of homologous ChAdOx1 nCov-19 or mRNA-1273 and heterologous vaccination were extracted from previous studies for demonstration. The reductions in NtAb titers of homologous vaccination against Beta, Delta, and Omicron variants were obtained from literatures. A Bayesian inversion method was used to derive CoP from homologous to mix-match vaccine. Findings The predicted efficacy of ChAdOx1 nCov-19 and mRNA-1273 for Wuhan or D614G strains was 93 % (89 %-97 %). Given 8 âˆ¼ 11-fold, 2 âˆ¼ 5.5-fold, and 32.5 âˆ¼ 36-fold reduction of NtAb for Beta, Delta, and Omicron variants compared with D614G, the corresponding predictive efficacy of the mix-match ranged from 75.63 % to 73.87 %, 84.87 % to 81.25 %, and 0.067 % to 0.059 %, respectively. Interpretations While ChAdOx1 nCov-19 and mRNA-1273 used for demonstrating how to timely evaluate CoP for the mix-match vaccine still provides clinical efficacy against Beta and Delta VOCs but it appears ineffective for Omicron variants, which highlights the urgent need for next generation vaccine against Omicron variant.

Superrepellent Doubly Reentrant Geometry Promotes Antibiofouling and Prevention of Coronavirus Contamination

The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID‐19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID‐19 pandemic. The findings demonstrate that a unique fabricated doubly reentrant topology (DRT) structure carries remarkable superrepellent properties against biofouling of protein, blood, bacteria, and viruses. Moreover, this characteristic results from a highly minimized contact area and still exists even if the DRT surface is made of a hydrophilic material, such as silicon oxide.

Outbreak of respiratory syncytial virus subtype ON1 among children during COVID-19 pandemic in Southern Taiwan.

BACKGROUND: The regional respiratory syncytial virus (RSV) outbreak in southern Taiwan in late 2020 followed the surge of RSV cases in the national surveillance data and displayed distinct clinical features. This study investigated RSV epidemiology in the most recent five years and compared the clinical manifestations of this outbreak with non-outbreak period. METHODS: Medical records of RSV-infected children at the National Cheng Kung University Hospital from January 2016 to December 2020 were retrospectively retrieved from hospital-based electronic medical database. Cases of RSV infection were identified by RSV antigen positive and/or RSV isolated from respiratory specimens. The demographic, clinical presentations, and laboratory data were recorded. The RSV isolates in 2020 was sequenced for phylogenetic analysis. RESULTS: Overall, 442 RSV-infected cases were retrieved and 42.1% (186 cases) clustered in late 2020. The 2020 outbreak started in September, peaked in November, and lasted for 3 months. 2020 RSV-infected children were older (2.3 ± 2.2 years vs. 1.0 ± 1.0 years), more likely to be diagnosed with bronchopneumonia (57.5% vs. 31.6%), but also had a lower hospitalization rate, shorter hospital stay, less oxygen use, and less respiratory distress than those in 2016-2019 (all p value < 0.05). The RSV isolates in 2020 belonged to RSV-A subtype ON1 but were phylogenetically distinct from the ON1 strains prevalent in Taiwan previously. CONCLUSION: The 2020 RSV outbreak was led by the novel RSV-A subtype ON1 variant with clinical manifestations distinct from previous years. Continuous surveillance of new emerging variants of respiratory viruses in the post-pandemic era is warranted.

Translated Emission Pathways (TEPs): Long-Term Simulations of COVID-19 CO2 Emissions and Thermosteric Sea Level Rise Projections.

Within the scientific community, climate models have been established to relate long-term emission scenarios to their respective environmental response. Although data at high resolutions can be obtained, this research framework is often computationally complex and offers limited readability for the general public. With the COVID-19 pandemic bringing forth a new sense of lifestyle and reduced human activity, the CO2 emission data related to this global event can be used to illustrate the context of climate science to a broader audience. This study proposes a series of translated emission pathways (TEPs) that consist of CO2 emission patterns from the various phases of COVID-19 response and demonstrate a resemblance to the forcing scenarios utilized within climate research. A simple climate model and radiative forcing expression are used to parameterize the CO2 emission data from the TEPs to its respective atmospheric conditions. Thermosteric sea level rise is used as a metric of environmental impact to highlight the differences between the TEPs. By referencing the COVID-19 pandemic and establishing a linear research framework, this study introduces climate research to the general public and serves as a call to action for environmental responsibility.

Association of Reactogenicity with Immunogenicity of the ChAdOx1 nCoV-19 Vaccine in Patients Undergoing Hemodialysis.

The aim of our study was to determine whether local and systemic reactions following SARS-CoV-2 vaccination are predictive of immunogenicity in patients undergoing hemodialysis. We used an established questionnaire to survey 206 hemodialysis patients without prior SARS-CoV-2 infection regarding solicited local (pain, redness, and swelling) and systemic reactions (fatigue, headache, muscle and joint pain, nausea or vomiting, abdominal pain, diarrhea, and fever) within 7 days after receiving 1 dose of the ChAdOx1 nCoV-19 vaccine for SARS-CoV-2. The primary outcome was seroconversion of anti-SARS-CoV-2 IgG (≥50 AU/mL) at 28 days after vaccination. Local and systemic reactions were reported by 80 (38.8%) and 119 (57.8%) patients, respectively. A total of 138 (67.0%) patients developed an antibody response. Responders were younger, had a lower prevalence of coronary artery disease and use of immunosuppressants, and had a higher body mass index and lymphocyte count. In addition, a greater percentage of responders than non-responders reported reactogenicity. In multivariate logistic regression analyses, fever (OR 2.70 [95% CI 1.12-6.50]) and total symptom score (OR 1.33 [95% CI, 1.05-1.68], per one increase) remained strongly associated with a greater humoral response. In conclusion, higher reactogenicity may identify hemodialysis patients who are more responsive to SARS-CoV-2 vaccination.

Estimating global burden of COVID-19 with disability-adjusted life years and value of statistical life metrics.

BACKGROUND: Global burden of COVID-19 has not been well studied, disability-adjusted life years (DALYs) and value of statistical life (VSL) metrics were therefore proposed to quantify its impacts on health and economic loss globally. METHODS: The life expectancy, cases, and death numbers of COVID-19 until 30th April 2021 were retrieved from open data to derive the epidemiological profiles and DALYs (including years of life lost (YLL) and years loss due to disability (YLD)) by four periods. The VSL estimates were estimated by using hedonic wage method (HWM) and contingent valuation method (CVM). The estimate of willingness to pay using CVM was based on the meta-regression mixed model. Machine learning method was used for classification. RESULTS: Globally, DALYs (in thousands) due to COVID-19 was tallied as 31,930 from Period I to IV. YLL dominated over YLD. The estimates of VSL were US$591 billion and US$5135 billion based on HWM and CVM, respectively. The estimate of VSL increased from US$579 billion in Period I to US$2160 billion in Period IV using CVM. The higher the human development index (HDI), the higher the value of DALYs and VSL. However, there exits the disparity even at the same level of HDI. Machine learning analysis categorized eight patterns of global burden of COVID-19 with a large variation from US$0.001 billion to US$691.4 billion. CONCLUSION: Global burden of COVID-19 pandemic resulted in substantial health and value of life loss particularly in developed economies. Classifications of such health and economic loss is informative to early preparation of adequate resource to reduce impacts.