Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19.

SARS-CoV-2 infection causes severe COVID-19 in some patients and mild in others. Dysfunctional innate immune responses have been identified to contribute to COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell multi-omics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified genes that were potentially regulated by differential chromatin accessibility. Then, sub-clustering and motif-enrichment analyses reveals disease condition-specific regulation by transcription factors and their targets, including an interaction between C/EBPs and a long-noncoding RNA LUCAT1, which we validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (AsoC) in COVID-19 patients and identified a SNP rs6800484-C, which is associated with lower expression of CCR2 and may contribute to higher viral loads and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to COVID-19.

Changes in Public Sentiment under the Background of Major Emergencies-Taking the Shanghai Epidemic as an Example.

The occurrence of major health events can have a significant impact on public mood and mental health. In this study, we selected Shanghai during the 2019 novel coronavirus pandemic as a case study and Weibo texts as the data source. The ERNIE pre-training model was used to classify the text data into five emotional categories: gratitude, confidence, sadness, anger, and no emotion. The changes in public sentiment and potential influencing factors were analyzed with the emotional sequence diagram method. We also examined the causal relationship between the epidemic and public sentiment, as well as positive and negative emotions. The study found: (1) public sentiment during the epidemic was primarily affected by public behavior, government behavior, and the severity of the epidemic. (2) From the perspective of time series changes, the changes in public emotions during the epidemic were divided into emotional fermentation, emotional climax, and emotional chaos periods. (3) There was a clear causal relationship between the epidemic and the changes in public emotions, and the impact on negative emotions was greater than that of positive emotions. Additionally, positive emotions had a certain inhibitory effect on negative emotions.

Hotspots and trends in ophthalmology in recent 5 years: Bibliometric analysis in 2017-2021.

Purpose: The purpose of this study was to investigate the hotspots and research trends of ophthalmology research. Method: Ophthalmology research literature published between 2017 and 2021 was obtained in the Web of Science Core Collection database. The bibliometric analysis and network visualization were performed with the VOSviewer and CiteSpace. Publication-related information, including publication volume, citation counts, countries, journals, keywords, subject categories, and publication time, was analyzed. Results: A total of 10,469 included ophthalmology publications had been cited a total of 7,995 times during the past 5 years. The top countries and journals for the number of publications were the United States and the Ophthalmology. The top 25 global high-impact documents had been identified using the citation ranking. Keyword co-occurrence analysis showed that the hotspots in ophthalmology research were epidemiological characteristics and treatment modalities of ocular diseases, artificial intelligence and fundus imaging technology, COVID-19-related telemedicine, and screening and prevention of ocular diseases. Keyword burst analysis revealed that "neural network," "pharmacokinetics," "geographic atrophy," "implementation," "variability," "adverse events," "automated detection," and "retinal images" were the research trends of research in the field of ophthalmology through 2021. The analysis of the subject categories demonstrated the close cooperation relationships that existed between different subject categories, and collaborations with non-ophthalmology-related subject categories were increasing over time in the field of ophthalmology research. Conclusions: The hotspots in ophthalmology research were epidemiology, prevention, screening, and treatment of ocular diseases, as well as artificial intelligence and fundus imaging technology and telemedicine. Research trends in ophthalmology research were artificial intelligence, drug development, and fundus diseases. Knowledge from non-ophthalmology fields is likely to be more involved in ophthalmology research.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern in real-world: a literature review and meta-analysis.

Knowing vaccine effectiveness (VE) against variants of concern (VOCs) in the real-world setting is essential for public health decision-making. A systematic landscape of the VE against a series of clinical outcomes caused by the VOCs in the real-world setting is needed. We systematically searched for studies that evaluated VE against VOCs in the real-world setting and collected individual data. We identified 113 studies meeting the eligibility criteria. We found full vaccination provided strong protection against each clinical outcome with summary VE ranging from 86.8% to 96.0% Alpha, moderate protection against infection caused by Beta, Gamma and Delta with summary VE ranging from 70.9% to 72.8%, strong protection against severe disease caused by Delta with summary VE ranging from 84.9% to 90.3%, limited protection with summary VE of 23.5% (95% CI, 17.0-29.5) against infection and moderate protection with summary VE ranging from 56.5% to 82.4% against severe diseases caused by Omicron. Booster vaccination can provide a substantial improvement in protection against Delta and Omicron, but not as much as the Delta. The meta-regression analysis showed that the VE against the Omicron wanned over time, and the VE against hospitalization declined relatively slowly, compared to against infection. Those findings supported the need for public health measures, increasing booster vaccination coverage in response to current and new infectious waves driven by variants and developing broadly protective vaccines to confront virus evolution.

Hotspots and trends in ophthalmology in recent 5 years: Bibliometric analysis in 2017–2021

Purpose The purpose of this study was to investigate the hotspots and research trends of ophthalmology research. Method Ophthalmology research literature published between 2017 and 2021 was obtained in the Web of Science Core Collection database. The bibliometric analysis and network visualization were performed with the VOSviewer and CiteSpace. Publication-related information, including publication volume, citation counts, countries, journals, keywords, subject categories, and publication time, was analyzed. Results A total of 10,469 included ophthalmology publications had been cited a total of 7,995 times during the past 5 years. The top countries and journals for the number of publications were the United States and the Ophthalmology. The top 25 global high-impact documents had been identified using the citation ranking. Keyword co-occurrence analysis showed that the hotspots in ophthalmology research were epidemiological characteristics and treatment modalities of ocular diseases, artificial intelligence and fundus imaging technology, COVID-19-related telemedicine, and screening and prevention of ocular diseases. Keyword burst analysis revealed that “neural network,” “pharmacokinetics,” “geographic atrophy,” “implementation,” “variability,” “adverse events,” “automated detection,” and “retinal images” were the research trends of research in the field of ophthalmology through 2021. The analysis of the subject categories demonstrated the close cooperation relationships that existed between different subject categories, and collaborations with non-ophthalmology-related subject categories were increasing over time in the field of ophthalmology research. Conclusions The hotspots in ophthalmology research were epidemiology, prevention, screening, and treatment of ocular diseases, as well as artificial intelligence and fundus imaging technology and telemedicine. Research trends in ophthalmology research were artificial intelligence, drug development, and fundus diseases. Knowledge from non-ophthalmology fields is likely to be more involved in ophthalmology research.

The Genetic Risk for COVID-19 Severity Is Associated With Defective Immune Responses.

Recent genome-wide association studies (GWASs) of COVID-19 patients of European ancestry have identified genetic loci significantly associated with disease severity. Here, we employed the detailed clinical, immunological and multi-omics dataset of the Human Functional Genomics Project (HFGP) to explore the physiological significance of the host genetic variants that influence susceptibility to severe COVID-19. A genomics investigation intersected with functional characterization of individuals with high genetic risk for severe COVID-19 susceptibility identified several major patterns: i. a large impact of genetically determined innate immune responses in COVID-19, with ii. increased susceptibility for severe disease in individuals with defective cytokine production; iii. genetic susceptibility related to ABO blood groups is probably mediated through the von Willebrand factor (VWF) and endothelial dysfunction. We further validated these identified associations at transcript and protein levels by using independent disease cohorts. These insights allow a physiological understanding of genetic susceptibility to severe COVID-19, and indicate pathways that could be targeted for prevention and therapy.

Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19.

The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in 14 convalescent COVID-19 and 15 healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays minor changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1Ra and IFN-γ was higher in convalescent individuals. In conclusion, we propose that despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.

Single-cell RNA sequencing reveals induction of distinct trained-immunity programs in human monocytes.

Trained immunity refers to the long-lasting memory traits of innate immunity. Recent studies have shown that trained immunity is orchestrated by sustained changes in epigenetic marks and metabolic pathways, leading to an altered transcriptional response to a second challenge. However, the potential heterogeneity of trained-immunity induction in innate immune cells has not been explored. In this study, we demonstrate cellular transcriptional programs in response to 4 different inducers of trained immunity in monocyte populations at single-cell resolution. Specifically, we identified 3 monocyte subpopulations upon the induction of trained immunity, and replicated these findings in an in vivo study. In addition, we found gene signatures consistent with these functional programs in patients with ulcerative colitis, sepsis, and COVID-19, suggesting the impact of trained-immunity programs in immune-mediated diseases.

Real-world effectiveness of COVID-19 vaccines: a literature review and meta-analysis.

OBJECTIVE: To estimate the coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) against concerned outcomes in real-world settings. METHODS: Studies reporting COVID-19 VE from August 6, 2020 to October 6, 2021 were included. The summary VE (with 95% confidence intervals (95% CI)) against disease related to COVID-19 was estimated. The results were presented in forest plots. Predefined subgroup analyses and sensitivity analyses were also performed. RESULTS: A total of 51 records were included in this meta-analysis. In fully vaccinated populations, the VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19-related hospitalization, admission to the intensive care unit, and death was 89.1% (95% CI 85.6-92.6%), 97.2% (95% CI 96.1-98.3%), 97.4% (95% CI 96.0-98.8%), and 99.0% (95% CI 98.5-99.6%), respectively. The VE against infection in the general population aged ≥16 years, the elderly, and healthcare workers was 86.1% (95% CI 77.8-94.4%), 83.8% (95% CI 77.1-90.6%), and 95.3% (95% CI 92.0-98.6%), respectively. For those fully vaccinated against infection, the observed effectiveness of the Pfizer-BioNTech vaccine was 91.2% and of the Moderna vaccine was 98.1%, while the effectiveness of the CoronaVac vaccine was found to be 65.7%. CONCLUSIONS: The COVID-19 vaccines are highly protective against SARS-CoV-2-related diseases in real-world settings.

Induction of trained immunity by influenza vaccination - impact on COVID-19.

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.

Implementation and evaluation of a novel real-time multiplex assay for SARS-CoV-2: in-field learnings from a clinical microbiology laboratory.

The unprecedented scale of testing required to effectively control the coronavirus disease (COVID-19) pandemic has necessitated urgent implementation of rapid testing in clinical microbiology laboratories. To date, there are limited data available on the analytical performance of emerging commercially available assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and integration of these assays into laboratory workflows. Here, we performed a prospective validation study of a commercially available assay, the AusDiagnostics Coronavirus Typing (8-well) assay. Respiratory tract samples for SARS-CoV-2 testing were collected between 1 March and 25 March 2020. All positive samples and a random subset of negative samples were sent to a reference laboratory for confirmation. In total, 2673 samples were analysed using the Coronavirus Typing assay. The predominant sample type was a combined nasopharyngeal/throat swab (2640/2673; 98.8%). Fifty-four patients were positive for SARS-CoV-2 (2.0%) using the Coronavirus Typing assay; 53/54 (98.1%) positive results and 621/621 (100%) negative results were concordant with the reference laboratory. Compared to the reference laboratory gold standard, sensitivity of the Coronavirus Typing assay for SARS-CoV-2 was 100% (95% CI 93.2-100%), specificity 99.8% (95% CI 99.1-100%), positive predictive value 98.1% (95% CI 90.2-99.7%) and negative predictive value 100% (95% CI 99.4-100%). In many countries, standard regulatory requirements for the introduction of new assays have been replaced by emergency authorisations and it is critical that laboratories share their post-market validation experiences, as the consequences of widespread introduction of a suboptimal assay for SARS-CoV-2 are profound. Here, we share our in-field experience, and encourage other laboratories to follow suit.

Meltblown fabric vs nanofiber membrane, which is better for fabricating personal protective equipments.

The coronavirus disease 2019 (COVID-19) pandemic has led to a great demand on the personal protection products such as reusable masks. As a key raw material for masks, meltblown fabrics play an important role in rejection of aerosols. However, the electrostatic dominated aerosol rejection mechanism of meltblown fabrics prevents the mask from maintaining the desired protective effect after the static charge degradation. Herein, novel reusable masks with high aerosols rejection efficiency were fabricated by the introduction of spider-web bionic nanofiber membrane (nano cobweb-biomimetic membrane). The reuse stability of meltblown and nanofiber membrane mask was separately evaluated by infiltrating water, 75% alcohol solution, and exposing under ultraviolet (UV) light. After the water immersion test, the filtration efficiency of meltblown mask was decreased to about 79%, while the nanofiber membrane was maintained at 99%. The same phenomenon could be observed after the 75% alcohol treatment, a high filtration efficiency of 99% was maintained in nanofiber membrane, but obvious negative effect was observed in meltblown mask, which decreased to about 50%. In addition, after long-term expose under UV light, no filtration efficiency decrease was observed in nanofiber membrane, which provide a suitable way to disinfect the potential carried virus. This work successfully achieved the daily disinfection and reuse of masks, which effectively alleviate the shortage of masks during this special period.

Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment.

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

COVID-19 and cutaneous manifestations: a systematic review.

The cutaneous manifestations of COVID-19 patients have been increasingly reported, but not summarized, and the potential mechanisms remain to be investigated. Herein, we performed a comprehensive review of literatures (from inception to 30 May 2020) using PubMed, CNKI, medRxiv and bioRxiv with the terms "((novel coronavirus) OR (2019 novel coronavirus) OR (2019-nCoV) OR (Coronavirus disease 2019) OR (COVID-19) OR (SARS-CoV-2)) AND ((Dermatology) OR (skin) OR (rash) OR (cutaneous))" and "((ACE2) OR (Angiotensin-converting enzyme)) AND ((skin) OR (epidermis) OR (dermis))." Totally, 44 articles met the inclusion criteria. A total of 507 patients with cutaneous manifestations were summarized, and 96.25% patients were from Europe. The average age of the patients was 49.03 (range: 5-91) with a female ratio of 60.44%. The skin lesions were polymorphic, and erythema, chilblain-like and urticarial lesions were most common, occurring on an average of 9.92 days (range: 1-30) after the onset of systemic symptoms. The receptor of SARS-CoV-2, ACE2, was found to be expressed on skin, mainly on keratinocytes. Our review systematically presented the clinical characteristics of 507 patients and showed that skin might be the potential target of the infection according to ACE2 expression. More work should be done to better understand the underlying pathogenesis.