Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. (preprint)

During the COVID-19 pandemic it was widely described that certain individuals infected by SARS-CoV-2 experience persistent disease signs and symptoms, Long COVID, which in some cases is very severe with life changing consequences. To maximize our chances of identifying the underpinnings of this illness, we have focused on 121 of the most severe cases from >1000 patients screened in specialized clinics in Sweden and Belgium. We restricted this study to subjects with objective measures of organ damage or dysfunction, >3 months following a verified, but mild-to-moderate SARS-CoV-2 infection. By performing systems-level immunological testing and comparisons to controls fully convalescent following a similar mild/moderate COVID-19 episode, we identify elevated serological responses to SARS-CoV-2 in severe Long COVID suggestive of chronic antigen stimulation. Persistent viral reservoirs have been proposed in Long COVID and using multiple orthogonal methods for detection of SARS-CoV-2 RNA and protein in plasma we identify a subset of patients with detectable antigens, but with minimal overlap across assays, and no correlation to symptoms or immune measurements. Elevated serologic responses to SARS-CoV-2 on the other hand were inversely correlated with clonally expanded memory CD8+ T cells, indicating that restrained clonal expansion enables viral persistence, chronic antigen exposure and elevated IgG responses, even if antigen-detection in blood is not universally possible.

Clinical and multimodal imaging features of acute macular neuroretinopathy lesions following recent SARS-CoV-2 infection.

AIM: To describe the clinical characteristics of eyes using multimodal imaging features with acute macular neuroretinopathy (AMN) lesions following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Retrospective case series study. From December 18, 2022 to February 14, 2023, previously healthy cases within 1-week infection with SARS-CoV-2 and examined at Tianjin Eye Hospital to confirm the diagnosis of AMN were included in the study. Totally 5 males and 9 females [mean age: 29.93±10.32 (16-49)y] were presented for reduced vision, with or without blurred vision. All patients underwent best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, indirect fundoscopy. Simultaneously, multimodal imagings fundus photography (45° or 200° field of view) was performed in 7 cases (14 eyes). Near infrared (NIR) fundus photography was performed in 9 cases (18 eyes), optical coherence tomography (OCT) in 5 cases (10 eyes), optical coherence tomography angiography (OCTA) in 9 cases (18 eyes), and fundus fluorescence angiography (FFA) in 3 cases (6 eyes). Visual field was performed in 1 case (2 eyes). RESULTS: Multimodal imaging findings data from 14 patients with AMN were reviewed. All eyes demonstrated different extent hyperreflective lesions at the level of the inner nuclear layer and/or outer plexus layer on OCT or OCTA. Fundus photography (45° or 200° field of view) showed irregular hypo-reflective lesion around the fovea in 7 cases (14 eyes). OCTA demonstrated that the superficial retinal capillary plexus (SCP) vascular density, deep capillary plexus (DCP) vascular density and choriocapillaris (CC) vascular density was reduced in 9 case (18 eyes). Among the follow-up cases (2 cases), vascular density increased in 1 case with elevated BCVA; another case has vascular density decrease in one eye and basically unchanged in other eye. En face images of the ellipsoidal zone and interdigitation zone injury showed a low wedge-shaped reflection contour appearance. NIR image mainly show the absence of the outer retinal interdigitation zone in AMN. No abnormal fluorescence was observed in FFA. Corresponding partial defect of the visual field were visualized via perimeter in one case. CONCLUSION: The morbidity of SARS-CoV-2 infection with AMN is increased. Ophthalmologists should be aware of the possible, albeit rare, AMN after SARS-CoV-2 infection and focus on multimodal imaging features. OCT, OCTA, and infrared fundus phase are proved to be valuable tools for detection of AMN in patients with SARS-CoV-2.

Identification of Age-Related Characteristic Genes Involved in Severe COVID-19 Infection Among Elderly Patients using Machine Learning and Immune Cell Infiltration Analysis (preprint)

Background Elderly patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at higher risk of severe clinical manifestation, extended hospitalization, and increased mortality. Those patients are more likely to experience persistent symptoms and exacerbate the condition of basic diseases with long COVID-19 syndrome. However, the molecular mechanisms underlying severe COVID-19 in the elderly patients remain unclear. Our study aims to investigate the function of the interaction between disease-characteristic genes and immune cell infiltration in patients with severe COVID-19 infection.Methods COVID-19 datasets (GSE164805 and GSE180594) and aging dataset (GSE69832) were obtained from the Gene Expression Omnibus (GEO) database. The combined different expression genes (DEGs) were subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Diseases Ontology (DO) functional enrichment analysis, Gene Set Enrichment Analysis (GSEA), machine learning, and immune cell infiltration analysis.Results GO and KEGG enrichment analysis revealed that the eight DEGs (IL23A, PTGER4, PLCB1, IL1B, CXCR1, C1QB, MX2, ALOX12) were mainly involved in inflammatory mediator regulation of TRP channels, coronavirus disease-COVID-19, and cytokine activity signaling pathways. Two-degree algorithm (LASSO and SVM-RFE) and correlation analysis showed that the seven DEGs upregulated the immune cells of macrophages M0/M1, memory B cells, gramma delta T cell, dendritic cell resting and master cell resisting.Conclusion Our study identified seven hallmark genes that can serve as disease-characteristic genes and target immune cells infiltrated in severe COVID-19 patients among the elderly population, which may contribute to the study of pathogenesis and the evaluation of diagnosis and prognosis in aging patients infected with severe COVID-19.

Excess mortality in Ukraine during the course of COVID-19 pandemic in 2020-2021.

In this work, the COVID-19 pandemic burden in Ukraine is investigated retrospectively using the excess mortality measures during 2020-2021. In particular, the epidemic impact on the Ukrainian population is studied via the standardized both all-cause and cause-specific mortality scores before and during the epidemic. The excess mortality counts during the pandemic were predicted based on historic data using parametric and nonparametric modeling and then compared with the actual reported counts to quantify the excess. The corresponding standardized mortality P-score metrics were also compared with the neighboring countries. In summary, there were three "waves" of excess all-cause mortality in Ukraine in December 2020, April 2021 and November 2021 with excess of 32%, 43% and 83% above the expected mortality. Each new "wave" of the all-cause mortality was higher than the previous one and the mortality "peaks" corresponded in time to three "waves" of lab-confirmed COVID-19 mortality. The lab-confirmed COVID-19 mortality constituted 9% to 24% of the all-cause mortality during those three peak months. Overall, the mortality trends in Ukraine over time were similar to neighboring countries where vaccination coverage was similar to that in Ukraine. For cause-specific mortality, the excess observed was due to pneumonia as well as circulatory system disease categories that peaked at the same times as the all-cause and lab-confirmed COVID-19 mortality, which was expected. The pneumonias as well as circulatory system disease categories constituted the majority of all cases during those peak times. The seasonality in mortality due to the infectious and parasitic disease category became less pronounced during the pandemic. While the reported numbers were always relatively low, alcohol-related mortality also declined during the pandemic.

Effect of monovalent and bivalent live attenuated vaccines against QX-like IBV infection in young chickens.

Since 1999, QX-like (GI-19) avian infectious bronchitis viruses have been the predominant strains in China till now. Vaccination is the most effective way to control the disease, while live attenuated vaccine is widely used. In the current research, we evaluated the effect of several monovalent and bivalent live IBV vaccines in young chickens against the QX-like (GI-19) IBV infection. The results showed that monovalent 4/91 and bivalent Ma5+LDT3 vaccines could provide efficient protection in day-old chickens that reduced morbidity and mortality, ameliorated histopathology lesions, and reduced viral loads were observed. These data suggest that vaccination through nasal route with monovalent 4/91 or bivalent Ma5+LDT3 in day-old chickens could serve a safe and effective vaccination strategy for controlling QX-like (GI-19) infectious bronchitis virus.

Evolution of Immune Evasion and Host Range Expansion by the SARS-CoV-2 B.1.1.529 (Omicron) Variant.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has rapidly become the dominant strain, with an unprecedented number of mutations within its spike gene. However, it remains unknown whether these variants have alterations in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies and entry inhibitors. In this study, we found that Omicron spike has evolved to escape neutralization by three-dose inactivated-vaccine-elicited immunity but remains sensitive to an angiotensin-converting enzyme 2 (ACE2) decoy receptor. Moreover, Omicron spike could use human ACE2 with a slightly increased efficiency while gaining a significantly increased binding affinity for a mouse ACE2 ortholog, which exhibits limited binding with wild-type (WT) spike. Furthermore, Omicron could infect wild-type C57BL/6 mice and cause histopathological changes in the lungs. Collectively, our results reveal that evasion of neutralization by vaccine-elicited antibodies and enhanced human and mouse ACE2 receptor engagement may contribute to the expanded host range and rapid spread of the Omicron variant. IMPORTANCE The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Compared with the ancestor strain isolated in early 2020, the spike protein of Omicron utilizes the human ACE2 receptor with enhanced efficiency while gaining the ability to utilize mouse ACE2 for cell entry. Moreover, Omicron could infect wild-type mice and cause pathological changes in the lungs. These results reveal that antibody evasion, enhanced human ACE2 utilization, and an expanded host range may contribute to its rapid spread.

Key mutations in the spike protein of SARS-CoV-2 affecting neutralization resistance and viral internalization.

To control the ongoing COVID-19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been developed. However, the rapid mutations of SARS-CoV-2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS-CoV-2, and then systematically assessed the susceptivity of these SARS-CoV-2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS-CoV-2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin-converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS-CoV-2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.

Effects of different stirrer modes on the physicochemical properties of vegetables during cooking

Summary The coronavirus disease‐19 (COVID‐19) pandemic caused dietary changes. Humans reduced social activities to prevent the spread of COVID‐19, which led to increasing demand for machines to help cook. This work studies the effect of different stirrer modes on the texture of celery, asparagus, green peppers, and spinach during the cooking process and the functional loss of components in vegetables by measuring the changes in vitamin C, total polyphenols, and total flavonoids. The results showed that colour changes and loss of nutrients in each vegetable varied under different stirrer modes. Stirring was found to be the best mode for cooking all four vegetables. In addition, there was a positive correlation between the a* value and functional components during the cooking process, which means that the colour difference and nutritional loss of vegetables can be modulated together. This study provides theoretical guidance for developing the stirring unit in a cooking machine. [ FROM AUTHOR]

Association between sleep duration and myopia among Chinese children during the COVID-19 pandemic: A cross-sectional study

Background The studies on the association between sleep duration and myopia are limited, and the evidence is inconsistent. This study aimed to evaluate the association between sleep duration and myopia, cycloplegic spherical equivalent (SE) and axial length (AL) among Chinese children during the Corona Virus Disease 2019 (COVID-19) pandemic. Methods The study was a cross-sectional study on Chinese children aged 6–18 years. The comprehensive ophthalmic examinations for children included cycloplegic SE, AL, and standardized questionnaires. The questionnaire included sleep duration, parental myopia, outdoor time, and continuous near work duration without breaks. Myopia was defined as SE ≤-0.50 diopters (D). Results A total of 1,140 children were included in the analyses, with 84.7% of myopic children and 74.4% of children's daily sleep duration being more than 8 h/d. In univariate regression analysis, compared with sleep duration < 8 h/d, children with sleep duration of 8–9 and >9 h/d were less myopia (p < 0.01 for all), and had less myopic SE (p < 0.01 for all), and shorter AL (p < 0.01 for all). After adjusting for age, gender, parental myopia, outdoor time, and continuous near work duration without breaks, sleep duration was not associated with myopia, cycloplegic SE, and AL (p > 0.05 for all). Conclusions This study showed sleep duration was related to myopia, cycloplegic SE, and AL among Chinese children during the COVID-19 pandemic-related lifestyles, but no independent association.

Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration.

Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-[Formula: see text]1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-[Formula: see text]1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-[Formula: see text]1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-[Formula: see text]1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration.

VirusRecom: an information-theory-based method for recombination detection of viral lineages and its application on SARS-CoV-2.

Genomic recombination is an important driving force for viral evolution, and recombination events have been reported for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Coronavirus Disease 2019 pandemic, which significantly alter viral infectivity and transmissibility. However, it is difficult to identify viral recombination, especially for low-divergence viruses such as SARS-CoV-2, since it is hard to distinguish recombination from in situ mutation. Herein, we applied information theory to viral recombination analysis and developed VirusRecom, a program for efficiently screening recombination events on viral genome. In principle, we considered a recombination event as a transmission process of ``information'' and introduced weighted information content (WIC) to quantify the contribution of recombination to a certain region on viral genome; then, we identified the recombination regions by comparing WICs of different regions. In the benchmark using simulated data, VirusRecom showed a good balance between precision and recall compared to two competing tools, RDP5 and 3SEQ. In the detection of SARS-CoV-2 XE, XD and XF recombinants, VirusRecom providing more accurate positions of recombination regions than RDP5 and 3SEQ. In addition, we encapsulated the VirusRecom program into a command-line-interface software for convenient operation by users. In summary, we developed a novel approach based on information theory to identify viral recombination within highly similar sequences, providing a useful tool for monitoring viral evolution and epidemic control.

Immune response to the mRNA COVID-19 vaccine in hemodialysis patients: cohort study (preprint)

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines.Methods: A transcriptomic analysis of the immune response to the Covid-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells (PBMCs) was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and seven days after the second dose (V2D7) using anti-Spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified six months after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response.Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with predominant T cell activity in controls one week after the first vaccination dose, compared to predominant myeloid cell activity in HD at this time point. HD demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p < 0.05). Anti-spike IgG remained elevated above baseline at six months in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development.Conclusion: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance hemodialysis subjects (HD) comparable to healthy controls (HC) and identify transcriptomic and clinical predictors of anti-Spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of end stage renal disease (ESRD). Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003

Human-in-the-loop Evaluation for Early Misinformation Detection: A Case Study of COVID-19 Treatments (preprint)

We present a human-in-the-loop evaluation framework for fact-checking novel misinformation claims and identifying social media messages that support them. Our approach extracts check-worthy claims, which are aggregated and ranked for review. Stance classifiers are then used to identify tweets supporting novel misinformation claims, which are further reviewed to determine whether they violate relevant policies. To demonstrate the feasibility of our approach, we develop a baseline system based on modern NLP methods for human-in-the-loop fact-checking in the domain of COVID-19 treatments. We make our data and detailed annotation guidelines available to support the evaluation of human-in-the-loop systems that identify novel misinformation directly from raw user-generated content.

Advances in "long COVID" syndrome

SARS-CoV-2 has rapidly spread across the world and infected hundreds of billions of people worldwide. As our understanding of this disease continues to increase, the knowledge of the complications and sequelaes of this disease is also growing. For the time being, such complications and sequelaes are collectively termed as Long COVID. Similar to the acute infection stage of COVID-19, Long COVID is also heterogeneous. This review discusses various persistent complications and sequelaes observed in multiple organ systems caused by Long COVID, in order to increase people's attention to the Long COVID patients and enable them to obtain better quality of life.

Case report: Myocarditis following COVID-19 protein subunit vaccination.

We report findings in a 34-year-old female patient who presented with fulminant myocarditis 8 days after receiving the first dose of the ZF2001 RBD-subunit vaccine against coronavirus disease 2019 (COVID-19). Autopsy showed severe interstitial myocarditis, including multiple patchy infiltrations of lymphocytes and monocytes in the myocardium of the left and right ventricular walls associated with myocyte degeneration and necrosis. This report highlights the details of clinical presentations and autopsy findings of myocarditis after ZF2001 (RBD-subunit vaccine) vaccination. The correlation between vaccination and death due to myocarditis is discussed.

The impact of COVID-19 lockdown on maternal and neonatal outcomes of uninfected woman in late pregnancy: A multicenter study in China (preprint)

Background COVID-19 pandemic has had direct and indirect impacts on health-care system and maternal and neonatal health, but no multicenter evidence from China of this effects has been undertaken. The purpose of this study was to investigate the impacts of COVID-19 lockdown on maternal and fetal outcomes in China.Methods This retrospective cohort study included 3540 women in their late pregnancy without COVID-19 who received perinatal healthcare in three hospitals in Wuhan, Shanghai and Haikou during COVID-19 lockdown period in 2020 or the non-lockdown period in 2019. Propensity-score matching was used to compare preterm birth (< 37 weeks) and its classification, very preterm birth (< 34 weeks), caesarean section and its indications, the length of hospital stay, birth weight and other pregnancy outcomes between two groups.Results Preterm births before 37 weeks’ gestation (5.4% vs. 5.3%, P = 0.83) and very preterm birth (0.7% vs. 0.8%, P = 0.58) were not significantly changed overall. But medical-induced preterm birth before 37 weeks’ gestation in Wuhan was decreased (0.8% vs. 1.7%, P = 0.04). The cesarean section for maternal factors was decreased (21.4% vs. 24.3%, P = 0.003). The length of maternal (4.2d vs 4.5d, P < 0.001) and neonatal (3.4d vs 3.7d, P < 0.001) hospital stay was shortened. No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; pregnancy-induced hypertension; preterm birth with premature rupture of membranes; low birthweight (< 2500 g); neonatal intensive care unit admission; or abnormal Apgar score.Conclusions This study demonstrated that there was protective impact of the COVID-19 lockdown on maternal and neonatal outcomes among women in their late pregnancy in China.

Does It Matter to Establish a Strategic Partnership for COVID-19 Prevention and Control? The Perspective of Multiple Distances in Emerging Economies

The rapid spread of the COVID-19 pandemic in early 2020 has impacted the politics, economy and society of countries around the world. The public health diplomacy system through which developed countries in Europe and America used to provide vertical one-way assistance to developing countries faces huge challenges. How emerging economies can cooperate to fight the pandemic on the basis of mutual trust and mutual benefit has become an urgent issue. In this paper, we examine the impact of political mutual trust on the effectiveness of pandemic prevention and control from the perspective of establishing strategic partnerships between emerging economies. Furthermore, taking into account the huge differences between emerging economies, this paper explores institutional distance, cultural distance, and geographical distance—the adjustment effect of the control effect. Studies have shown that the improvement of political mutual trust is conducive to the formation of a community of shared futures between countries and has a positive effect on curbing the spread of the pandemic. The increase of the three-dimensional distance of institutions, culture, and geography will weaken the effect of establishing strategic partners for pandemic prevention and control. This paper explores a new model of horizontal international cooperation among emerging economies, and provides a reference for emerging economies to deal with common globalization issues in the future.

Peer Support and Mental Health of Migrant Domestic Workers: A Scoping Review.

The effectiveness of peer support in improving mental health and well-being has been well documented for vulnerable populations. However, how peer support is delivered to migrant domestic workers (MDWs) to support their mental health is still unknown. This scoping review aimed to synthesize evidence on existing peer support services for improving mental health among MDWs. We systematically searched eight electronic databases, as well as grey literature. Two reviewers independently performed title/abstract and full-text screening, and data extraction. Twelve articles were finally included. Two types of peer support were identified from the included studies, i.e., mutual aid and para-professional trained peer support. MDWs mainly seek support from peers through mutual aid for emotional comfort. The study's findings suggest that the para-professional peer support training program was highly feasible and culturally appropriate for MDWs. However, several barriers were identified to affect the successful implementation of peer support, such as concerns about emotion contagion among peers, worries about disclosure of personal information, and lack of support from health professionals. Culture-specific peer support programs should be developed in the future to overcome these barriers to promote more effective mental health practices.