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1.
Cytotherapy ; JOUR(5):S35-S35, 24.
Article in English | EuropePMC | ID: covidwho-1812325

ABSTRACT

From SARS-CoV-1 outbreak in 2002 to the most recent SARS-CoV-2 pandemic (COVID-19), emergence of viral diseases has repeatedly threatened humanity over the recent decades. These viral diseases mainly cause respiratory symptoms, which can even lead to death when appropriate measures are not taken. In this study, we investigated whether adipose tissue-derived mesenchymal stem cell EVs (ASC-EVs) can attenuate acute lung injury (ALI) induced by H1N1 influenza A virus and SARS-CoV-2 and by what mechanism the ant-viral effect may occurs.

3.
World Journal of Traditional Chinese Medicine ; 8(4):463-490, 2022.
Article in English | EMBASE | ID: covidwho-2066828

ABSTRACT

Curcumae Longae Rhizoma (CLR) is the rhizome of Curcuma longa L. Pharmacological studies show that CLR can be used to treat cervical cancer, lung cancer, lupus nephritis, and other conditions. In this paper, we review botany, traditional application, phytochemistry, pharmacological activity, and pharmacokinetics of CLR. The literature from 1981 to date was entirely collected from online databases, such as Web of Science, Google Scholar, China Academic Journals full-text database (CNKI), Wiley, Springer, PubMed, and ScienceDirect. The data were also obtained from ancient books, theses and dissertations, and Flora Reipublicae Popularis Sinicae. There are a total of 275 compounds that have been isolated from CLR, including phenolic compounds, volatile oils, and others. The therapeutic effect of turmeric has been expanded from breaking blood and activating qi in the traditional sense to antitumor, anti-inflammatory, antioxidation, neuroprotection, antibacterial, hypolipidemic effects, and other benefits. However, the active ingredients and mechanisms of action related to relieving disease remain ill defined, which requires more in-depth research and verification at a clinical level.

4.
Covid-19's Economic Impact And Countermeasures In China ; : 213-250, 2022.
Article in English | Scopus | ID: covidwho-2053320
5.
International Journal of Qualitative Methods ; 21, 2022.
Article in English | Scopus | ID: covidwho-2021043

ABSTRACT

The COVID-19 pandemic, travel restrictions, and social distancing measures have made it difficult to observe, monitor, or manage urban life. To capture the experience of being in New York City during the first year of the COVID-19 pandemic, we used a novel method of remote ethnography to interview people who were walking the city. We developed the Walkie-Talkie Map to collect and present these interviews, enabling website visitors to see what the subject saw as they walked the route of their choice. Visitors can interactively scroll through the interview and have access to additional visualizations and imagery that contextualize the main narrative. Visitors are thus able to vicariously experience what it was like to be in New York City at the outset of the COVID-19 epidemic. This work provides a case study on how to perform observational research when geographic and bodily distance has become the norm. We discuss the advantages and limitations of our method and conclude with its contributions to the study of cities and for others looking to conduct remote observational research in different fields of knowledge. The Walkie-Talkie maps can be found on this url: https://www.socialdistancing.tech.cornell.edu/what-is-a-walike-talkie © The Author(s) 2022.

6.
Analytical Chemistry ; 94(33):11591-11599, 2022.
Article in English | Web of Science | ID: covidwho-2016508

ABSTRACT

The COVID-19 pandemic has led to a global crisis with devastating effects on public healthcare and the economy. Sensitive detection of SARS-CoV-2 is the key to diagnose and control its spread. The spike (S) protein is an abundant viral transmembrane protein and a suitable target protein for the selective recognition of SARS-CoV-2. Here, we report that with bovine serum albumin prescreening, a specific phage peptide targeting SARS-CoV-2 S1 protein was biopanned with the pIII phage display library. The identified phage #2 expressing the to the target with a dissociation constant of 3.45 +/- 0.58 nM. Furthermore, the identified peptide shows good specificity with a binding site at the N-terminal domain of the S1 subunit through a hydrogen bond network and hydrophobic interaction, supported by molecular docking. Then, a sandwiched phage-based enzyme-linked chemiluminescence immunoassay (ELCLIA) was established by using phage #2 as a bifunctional probe capable of SARS-CoV-2 S1 antigen recognition and signal amplification. After optimizing the conditions, the proposed phage ELCLIA exhibited good sensitivity, and as low as 78 pg/mL SARS-CoV-2 S1 could be detected. This method can be applied to detect as low as 60 transducing units (TU)/mL SARS-CoV-2 pseudovirus in 50% saliva. Therefore, specific phage peptides have good prospects as powerful biological recognition probes for immunoassay detection and biomedical applications.

7.
Acs Photonics ; 2022.
Article in English | Web of Science | ID: covidwho-2004745

ABSTRACT

Recent advances in the Medical Internet of Things (MIoT) and big data enable a prospering platform for pervasive healthcare and facilitate the transformation from hospital-centered to human-centered healthcare. Wearable devices as human interfaces provide first-hand data and real-time monitoring, which are key technologies in the MIoT. Several remarkable surveys have been conducted to summarize the recent progress in wearable sensors and systems for the MIoT and pervasive medicine. However, few have focused on wearable optical sensing (WOS) technologies, which is an emerging sensing modality in wearable devices. WOS can achieve high precision, high compatibility, high anti-interference, and low motion artifacts for human vital signal acquisition, which are particularly useful in special scenarios such as intensive care units (ICUs). These technologies can also be integrated with smart fabrics or mobile computing for out-of-hospital healthcare. This work provides the first literature review of WOS for pervasive medicine. We aim to systematically summarize the emerging WOS technologies in the MIoT for disease diagnosis and health monitoring. Specifically, this review covers the technical bases and design principles of major WOS technologies and their application domains for monitoring and treatment. We also discuss the opportunities and challenges, especially in the COVID-19 outbreak.

8.
Cytotherapy ; 24(5):S35, 2022.
Article in English | EMBASE | ID: covidwho-1996713

ABSTRACT

Background & Aim: From SARS-CoV-1 outbreak in 2002 to the most recent SARS-CoV-2 pandemic (COVID-19), emergence of viral diseases has repeatedly threatened humanity over the recent decades. These viral diseases mainly cause respiratory symptoms, which can even lead to death when appropriate measures are not taken. In this study, we investigated whether adipose tissue-derived mesenchymal stem cell EVs (ASC-EVs) can attenuate acute lung injury (ALI) induced by H1N1 influenza A virus and SARS-CoV-2 and by what mechanism the ant-viral effect may occurs. Methods, Results & Conclusion: EVs were isolated from ASC or HEK293T conditioned media by tangential flow filtration, and were characterized according to MISEV recommendation. Influenza A/ Puerto Rico/08/1934 (H1N1) and SARS-CoV-2 (NCCP43326) were used to model highly pathogenic human influenza A and SARS-CoV-2 virus infection, respectively, in mice and Syrian hamsters respectively. Treatment of ASC-EVs, from 0.15 x 109 to 5.0 x 109 particles/mL, showed inhibitory activities on cytopathic effects and replication of H1N1 and SARS-CoV-2 in MDCK cells and Vero E6 cells, respectively. In the mouse H1N1 influenza A virus induced acute lung injury (ALI) model, total of 4 daily injections of 1 x 1010 particles of ASC-EVs administration resulted in significantly increased survival rate by 30 – 40%, recovery of body weight, and improved clinical disease score from 9 dpi. In addition, ASC-EV treatment downregulated various inflammatory cytokines such as IL-1β, IL-6 and TNFα in lung tissue by up to 77%. In the Syrian hamster SARS-CoV-2 induced ALI model, total of 4 daily injections of ASC-EVs at a dose of 3 x 1010 or 1 x 1010 particles resulted recovery of body weights from 5 dpi, in a dose-dependent manner, by 9.7% - 12.75%. Further, ASC-EV treatment resulted in significant downregulation of viral genes and IL-1 beat in lung tissue. To elucidate the molecular mechanisms of the observed anti-viral effects of ASC-EVs, the role of multiple miRNAs and proteins present in the ASC-EVs were assessed in vitro. We identified one specific protein that conveyed anti-viral efficacy against the two studied viruses including SARS-CoV-2. Loss and gain of function studies revealed that this protein may be involved in the anti-viral efficacy of the ASC-EVs. Our findings support the concept that that ASC-EVs have anti-viral effects against virus induced ALI, which may have implications for the treatment of not only treatment COVID-19, but also future ALI-inducing virus diseases.

9.
Cancer Research ; 82(12), 2022.
Article in English | EMBASE | ID: covidwho-1986493

ABSTRACT

Angiotensin converting enzyme II (ACE2) is the cellular receptor of SARS-CoV-2. At present, ACE2 receptor is considered to be the key component in the SARS-CoV-2 infection and transmitting in the host. Among the cancer patients with COVID-19, the gastrointestinal cancer is the second most prevalent. The MethyLight and QASM assays were used to evaluated the genomic DNA 5mC methylation, while the CviAII enzyme-based 6mA-RE-qPCR was applied to determine motif-specific DNA 6mA methylation. The 6mA and 5mC methylation analyses of the long interspersed nuclear elements 1 (LINE1) were used to evaluate the global level of genomic 6mA and 5mC methylations, respectively. To investigate the role of ACE2 DNA methylation in regulating ACE2 expression, we performed a genome-wide methylation analysis in colorectal cancer samples collected at the Sixth Affiliated Hospital of Sun Yat-sen University. The DNA 5mC methylation of ACE2 promoter in tumor tissues were significantly lower than that in normal tissues, while the DNA 6mA methylation of ACE2 promoter in tumor tissues was significantly higher than that in normal tissues. In addition, the mRNA and protein expression of ACE2 in tumor tissues were lower than that in normal tissues. To explore the epigenetic regulation on ACE2 expression, we treated colon cancer cell lines with 5-Azacytidine and found ACE2 expression was upregulated after lowering the DNA 5mC methylation. The correlation analysis in patient cohort samples showed that ACE2 mRNA expression was positively correlated with DNA 5mC and negatively associated with DNA 6mA methylation. Next, a novel CRISPR-based tool was developed for sequence-specific 6mA editing on ACE2 promoter region, and it was applied in HCT116 cell to further confirm the regulatory role of DNA 6mA methylation in ACE2 mRNA expression. This tool was proved to be reliable with our findings that the CRISPR/dCas9-METTL3 tool could dramatically upregulate DNA 6mA methylation in ACE2 promoter, while the global level of genomic 6mA methylation remained unchanged. Both the mRNA and protein expression of ACE2 were significantly increased following a sequence-specific DNA 6mA editing in ACE2 promoter. In conclusion, we revealed the aberrant DNA 5mC and 6mA methylations in colorectal cancer, which upregulate ACE2 expression in colorectal cancer cells that may confer the susceptibility to SARS-CoV-2 infection. We developed a novel CRISPR-based tool that could realize site-directed 6mA methylation editing. Notably, the epigenetic regulation of DNA 6mA methylation on ACE2 expression provides an insight into the intersection of the biology of cancer, SARS-CoV-2 infection and organ-specific complication in COVID-19. Aberrant ACE2 methylation may serve as a biomarker and treatment target in these patients.

10.
International Journal on Semantic Web and Information Systems ; 18(1):19, 2022.
Article in English | Web of Science | ID: covidwho-1979482

ABSTRACT

Health information becomes importantly valuable for protecting public health in the current coronavirus situation. Knowledge-based information systems can play a crucial role in helping individuals to practice risk assessment and remote diagnosis. The authors introduce a novel approach that will develop causality-focused knowledge learning in a robust and transparent manner. Then, the machine gains the causality and probability knowledge for inference (thinking) and accurate prediction later. In addition, the hidden knowledge can be discovered beyond the existing understanding of the diseases. The whole approach is built on a causal probability description logic framework that combines natural language processing (NLP), causality analysis, and extended knowledge graph (KG) technologies. The experimental work has processed 801 diseases in total (from the UK NHS website linking with DBpedia datasets). As a result, the machine learnt comprehensive health causal knowledge and relations among the diseases, symptoms, and other facts efficiently.

11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(6):576-580, 2022.
Article in Chinese | MEDLINE | ID: covidwho-1974965

ABSTRACT

OBJECTIVE: To evaluate the clinical effect of awake prone positioning (APP) for common coronavirus disease 2019 (COVID-19) caused by Omicron variant. METHODS: Retrospectively analyze the clinical data of patients with COVID-19 caused by Omicron variant admitted by medical team of Tianjin Third Central Hospital during the period of supporting Tianjin COVID-19 designated hospital from January 8 to February 20, 2022. Patients who met the diagnostic criteria for common COVID-19 and had risk factors for developing severe disease or had pulse oxygen saturation (SpO2) <= 0.93 after exercise without supplementary oxygen were enrolled. Patients were divided into APP group and control group according to whether they completed the daily 12-hours APP in the first three days after enrollment. Demographic characteristics, clinical symptoms, COVID-19 vaccination status, laboratory examination, disease progression (progression to severe), time to nucleic acid negative conversion, length of hospital stay, and adverse reactions and tolerability [visual analog scale (VAS) score (the higher the score, the worse the tolerability] during APP were evaluated in two groups. Interleukin-6 (IL-6), C-reactive protein (CRP), SpO2/inhaled oxygen concentration (FiO2) ratio and ROX index (ROXI) were compared between two groups at enrollment, 3rd and 7th day after enrollment. RESULTS: There were no significant differences in demographic characteristics, clinical symptoms, vaccination rates of COVID-19 and laboratory tests between the two groups. There were no statistically significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups at the time of enrollment. Compared with the group at the time of enrollment, SpO2/FiO2 ratio and ROXI in APP group increased significantly at the 3rd day after enrollment [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (437.14, 457.10), ROXI: 25.40 (23.33, 25.93) vs. 22.57 (21.86, 24.40), all P < 0.05], and the levels of IL-6 and CRP in control group were significantly increased [IL-6 (ng/L): 18.30 (6.50, 37.75) vs. 7.40 (5.10, 11.15), CRP (mg/L): 11.46 (2.11, 17.96) vs. 4.11 (1.72, 9.05), all P < 0.05]. At the 3rd day of enrollment, the levels of IL-6 and CRP in APP group were significantly lower than those in control group [IL-6 (ng/L): 7.35 (4.35, 12.80) vs. 18.30 (6.50, 37.75), CRP (mg/L): 4.52 (1.98, 9.66) vs. 11.46 (2.11, 17.96), all P < 0.05], while SpO2/FiO2 ratio and ROXI were significantly higher than those in control group [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (441.90, 459.52), ROXI: 25.40 (23.33, 25.93) vs. 23.31 (22.10, 24.66), all P < 0.05]. At the 7th day of enrollment,there were no significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups. There were no severe cases in both groups. The time of nucleic acid negative conversion and length of hospital stay in APP group were significantly shorter than those in control group [10.0 (8.0, 12.0) days vs. 11.0 (9.0, 13.0) days, 12.0 (10.0, 14.0) days vs. 14.0 (12.0,16.0) days, respectively, all P < 0.05]. The main adverse reaction during APP was back pain, and the incidence in APP group was slightly lower than that in control group, but the difference was not statistically significant [17.9% (17/95) vs. 26.5% (27/102), P = 0.149]. VAS score in control group was significantly higher than that in APP group [score: 2.5 (2.0, 4.0) vs. 2.0 (1.0, 3.0), P = 0.004]. CONCLUSIONS: In common COVID-19 patients caused by Omicron variant with high risk factors for progression to severe disease or decreased oxygen reserve capacity, early APP can shorten the time of nucleic acid negative conversion and the length of hospital stay, but its effect on preventing disease progression cannot be determined.

12.
Gastroenterology ; 162(7):S-292, 2022.
Article in English | EMBASE | ID: covidwho-1967289

ABSTRACT

The COVID-19 pandemic impacted the life of people worldwide. We used a cross-sectional survey to evaluate the effects of pandemic on inflammatory bowel disease patients registered with Johns Hopkins. We assessed the methods used to minimize the risk of infection, coping mechanisms, changes in disease activity and management in the first 6 months of pandemic. Of the 405 patients who completed the questionnaire, 240 (58.8%) had Crohn's disease, 132 (32.6%) ulcerative colitis and 35 (8.6%) unclassified IBD.The median (IQR) age was 49 (28, 71). Two hundred seventy-three (67.4%) received biologics including patients on hospital-based (4.2%) infusions, outpatient-based infusions (26.7%) and home infusion (22.2%). Majority had other comorbidities, either heart (142/35.1%) or lung disease (19/ 4.7%), diabetes (22/5.4%), hypertension (77/19%), or obesity (13/3.2%). Most patients were at low risk for infection as they lived in a non-metropolitan area (291 patients, 71.8%), did not report close contact with a confirmed COVID-19 individual (373, 92.1%), did not travel to an area with high rates of COVID-19 (381, 94.1%) and did not use public transportation (379, 93.6%). All but 2 were taking protective measures such as use of N-95 mask (90, 22.2%), commercially (271, 66.9%) or homemade mask (208, 51.4%), sanitizer (363, 89.6%) or gloves (96, 23.7%). Additionally, patients used dietary/herbal supplements (55, 13.6%), dietary modifications (98, 24.2%) to support immunity (35, 8.6%), prevent an IBD flare (28, 6.9%), or minimize medications (48, 11.9%). The most common supplement used was Vitamin C (28, 50.9%), and D (42, 76.4%). Most (344, 84.7%) had no adjustments to their medications during pandemic, 31 (7.7%) discontinued their medication and 31 (7.7%) had to add a medication. Pandemic had, reportedly, no effect to the lives of 44 (20.9%) patients but 28 (13.3%) felt depressed, 70 (33.2%) anxious, 9 (4.3%) lost their income and 60 (28.4%) had other non-specified effects. The most common stress reduction techniques used were exercise (261, 64.4%), yoga (76, 18.8%), art therapy (23, 5.7%), music therapy (40, 9.9%), journaling (28, 6.9%), and guided Imagery (18, 4.4%). Fifty-eight (14.3%) used stress reduction medications. Eight (2%) reported SARS-CoV-2 infection. Median (IQR) age was 39 years (22,50)(Table 1). The majority had CD (6, 75%) and the infection was treated at home (6, 75%). One required admission to ICU. Infection led to worsening of the disease in 2 (25%). One (12.5%) discontinued IBD treatment. Our data suggest that most IBD patients followed low risk activities and were adherent to personal protective equipment and used stress reduction techniques and dietary supplements to cope with pandemic and avoid flares. Infection rates were low and the majority did not require admission to the hospital. In the majority infection did not cause an IBD exacerbation. (Table Presented)

13.
12th International Conference on Identification, Information and Knowledge in the internet of Things, IIKI 2021 ; 202:203-216, 2022.
Article in English | Scopus | ID: covidwho-1907683

ABSTRACT

We choose 100 stocks from China's markets and use their daily returns from January 3, 2013 to August 31, 2020 to investigate the risk situation in China's stock markets by exploring their correlations in the sample period. We build complexes and carry out topological data analysis on them. The persistence landscapes and their LP-norms show that there are three clear turbulent periods since 2013. The dates are then detected when the stocks are strongly correlated. As is well known, the financial risks easily break out and spread in such situations, so we call the dates critical dates for risks. We can also take them as the early warning signals for potential risks. We then construct planar maximal filtered graphs on the critical dates to help discover the systematically important companies. We find that they changed obviously in three different turbulent periods. It reminds us to analyze the risks' characteristics of the risks and implement risk prevention. The method combing topological data analysis and complex networks is shown to be effective in detecting critical information from markets, and hence is worth popularizing. © 2022 The Authors. Published by Elsevier B.V.

14.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-338449

ABSTRACT

Physical interactions between viral and host proteins are responsible for almost all aspects of the viral life cycle and the host's immune response. Studying viral-host protein-protein interactions is thus crucial for identifying strategies for treatment and prevention of viral infection. Here, we use high-throughput yeast two-hybrid and affinity purification followed by mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of both binary and co-complex interactions. We report a total of 739 high-confidence interactions, showing the highest overlap of interaction partners among published datasets as well as the highest overlap with genes differentially expressed in samples (such as upper airway and bronchial epithelial cells) from patients with SARS-CoV-2 infection. Showcasing the utility of our network, we describe a novel interaction between the viral accessory protein ORF3a and the host zinc finger transcription factor ZNF579 to illustrate a SARS-CoV-2 factor mediating a direct impact on host transcription. Leveraging our interactome, we performed network-based drug screens for over 2,900 FDA-approved/investigational drugs and obtained a curated list of 23 drugs that had significant network proximities to SARS-CoV-2 host factors, one of which, carvedilol, showed promising antiviral properties. We performed electronic health record-based validation using two independent large-scale, longitudinal COVID-19 patient databases and found that carvedilol usage was associated with a significantly lowered probability (17%-20%, P < 0.001) of obtaining a SARS-CoV-2 positive test after adjusting various confounding factors. Carvedilol additionally showed anti-viral activity against SARS-CoV-2 in a human lung epithelial cell line [half maximal effective concentration (EC 50 ) value of 4.1 microM], suggesting a mechanism for its beneficial effect in COVID-19. Our study demonstrates the value of large-scale network systems biology approaches for extracting biological insight from complex biological processes.

15.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-338321

ABSTRACT

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering currently dominant Omicron variants, China's current immunization level, and non-pharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. We found that due to high transmissibility, neither Omicron BA.1 or BA.2 could be contained by China's pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. As China's current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

17.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-336850

ABSTRACT

We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining a "Zero-COVID" policy in mainland China in light of currently dominant Omicron variants, China's current immunization level, and non-pharmaceutical intervention (NPI) strategies. We found that due to high transmissibility, neither Omicron BA.1 or BA.2 sublineages could be contained by China's Pre-Omicron non-pharmaceutical intervention strategies which were successful at sustaining the "Zero-COVID" policy until March 2022. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success without the necessity of population-wide lockdown. As China's current vaccination has yet to reach high coverage in older populations, non-pharmaceutical interventions remain essential tools to maintain low levels of infection while building protective population immunity, ensuring a smooth transition out of the pandemic phase, and minimizing the overall disease burden and societal costs.

18.
3rd International Conference on Machine Learning, Big Data and Business Intelligence, MLBDBI 2021 ; : 268-273, 2021.
Article in English | Scopus | ID: covidwho-1806953

ABSTRACT

In this paper, our group evaluates the effect of Covid-19 on the stock prices of the top 10 American airline companies and the NYSE Arca Airline Index using event study methodology. We accomplish this by comparing the Actual Returns and Expected Returns of an airline stock. We derive our Expected Return through a linear regression model between the airline stock returns and the market returns. We then subtract the Expected Return from the Actual Return to find the Abnormal Return. After that, we construct a confidence interval to test the significance of the Abnormal Return. If the Abnormal Return exceeds the confidence interval, we claim that Covid-19 had a significant effect on the stock price of our chosen Airlines. Our group's results showed that Covid-19 had a significant impact on the airline industry. We also looked at the impact of government-issued relief and mass vaccination, and we saw that airline stock prices recovered slowly but steadily. © 2021 IEEE.

19.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333746

ABSTRACT

BACKGROUND: Dementia-like cognitive impairment is an increasingly reported complication of SARS-CoV-2 infection. However, the underlying mechanisms responsible for this complication remain unclear. A better understanding of causative processes by which COVID-19 may lead to cognitive impairment is essential for developing preventive interventions. METHODS: In this study, we conducted a network-based, multimodal genomics comparison of COVID-19 and neurologic complications. We constructed the SARS-CoV-2 virus-host interactome from protein-protein interaction assay and CRISPR-Cas9 based genetic assay results, and compared network-based relationships therein with those of known neurological manifestations using network proximity measures. We also investigated the transcriptomic profiles (including single-cell/nuclei RNA-sequencing) of Alzheimer's disease (AD) marker genes from patients infected with COVID-19, as well as the prevalence of SARS-CoV-2 entry factors in the brains of AD patients not infected with SARS-CoV-2. RESULTS: We found significant network-based relationships between COVID-19 and neuroinflammation and brain microvascular injury pathways and processes which are implicated in AD. We also detected aberrant expression of AD biomarkers in the cerebrospinal fluid and blood of patients with COVID-19. While transcriptomic analyses showed relatively low expression of SARS-CoV-2 entry factors in human brain, neuroinflammatory changes were pronounced. In addition, single-nucleus transcriptomic analyses showed that expression of SARS-CoV-2 host factors ( BSG and FURIN ) and antiviral defense genes ( LY6E , IFITM2 , IFITM3 , and IFNAR1 ) was significantly elevated in brain endothelial cells of AD patients and healthy controls relative to neurons and other cell types, suggesting a possible role for brain microvascular injury in COVID-19-mediated cognitive impairment. Notably, individuals with the AD risk allele APOE E4/E4 displayed reduced levels of antiviral defense genes compared to APOE E3/E3 individuals. CONCLUSION: Our results suggest significant mechanistic overlap between AD and COVID-19, strongly centered on neuroinflammation and microvascular injury. These results help improve our understanding of COVID-19-associated neurological manifestations and provide guidance for future development of preventive or treatment interventions.

20.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333526

ABSTRACT

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. Systematic review registration: Prospero 2020 crd42020175648.

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