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1.
Autophagy ; : 1-15, 2022 Aug 31.
Article in English | MEDLINE | ID: covidwho-2282980

ABSTRACT

As a new emerging severe coronavirus, the knowledge on the SARS-CoV-2 and COVID-19 remains very limited, whereas many concepts can be learned from the homologous coronaviruses. Macroautophagy/autophagy is finely regulated by SARS-CoV-2 infection and plays important roles in SARS-CoV-2 infection and pathogenesis. This review will explore the subversion and mechanism of the autophagy-related machinery, vacuoles and organelle-specific autophagy during infection of SARS-CoV-2 and coronaviruses to provide meaningful insights into the autophagy-related therapeutic strategies for infectious diseases of SARS-CoV-2 and coronaviruses.

3.
J Med Virol ; 95(1): e28438, 2023 01.
Article in English | MEDLINE | ID: covidwho-2242677

ABSTRACT

Coronavirus disease 2019 (COVID-19), as well as its prevention and control measures, seriously affected people's livehood, which may have affected the body's level of vitamin D (VD). This study aimed to investigate the effect of the COVID-19 pandemic on the VD status of children in Zhengzhou, China. In this study, we included 12 272 children in 2019 (before the COVID-19 pandemic) and 16 495 children in 2020 (during the COVID-19 pandemic) to examine the changes in VD levels and deficiency rates among children before and during the COVID-19 pandemic. Total VD levels in 2020 were significantly higher than those in 2019 (26.56 [18.15, 41.40] vs. 25.98 [17.92, 40.09] ng/ml, p < 0.001). Further analysis revealed that during the COVID-19 pandemic control period in 2020, the VD levels in February, March, and April were lower than those in the same months of 2019, while the VD deficiency rates were significantly higher. Additionally, our data revealed that VD levels decreased significantly with age. Among children older than 6 years, the VD deficiency rate exceeded 50%. These results indicate that we should pay close attention to VD supplementation during the COVID-19 pandemic control period and in children older than 6 years of age.


Subject(s)
COVID-19 , Vitamin D Deficiency , Child , Humans , Vitamin D , Cross-Sectional Studies , Pandemics , COVID-19/epidemiology , Vitamins , Vitamin D Deficiency/epidemiology
5.
Front Pharmacol ; 13: 979400, 2022.
Article in English | MEDLINE | ID: covidwho-2229161

ABSTRACT

Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory effects of JTKY in poly(I:C)-induced pneumonia model mice were studied using untargeted metabolomics. Our results showed that JTKY treatment decreased the wet-to-dry ratio in the lung tissue, total protein concentration, and total cell count of the bronchoalveolar lavage fluid (BALF). Hematoxylin and Eosin (HE) and Masson staining indicated that the JTKY treatment alleviated the pathological changes and decreased the fibrotic contents in the lungs. JTKY treatment also decreased the expression of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α)] and increased the levels of immunomodulatory cytokines (IL-4 and IL-10) in the BALF and serum. Flow cytometry analysis showed that the JTKY treatment lowered the ratio of CD86+/CD206+ macrophages in the BALF, decreased inducible nitric oxide synthase (iNOS) level, and increased arginase 1 (Arg-1) level in lung. JTKY also lowered CD11b+Ly6G+ neutrophils in BALF and decreased myeloperoxidase (MPO) activity in lung. Moreover, it also elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) level in lung. Untargeted metabolomic analysis showed that the JTKY treatment could affect 19 metabolites in lung, such as L-adrenaline, L-asparagine, ornithine, and alpha-ketoglutaric acid. These metabolites are associated with the synthesis and degradation of ketone bodies, butanoate, alanine, aspartate, and glutamate metabolism, and tricarboxylic acid (TCA) cycle processes. In conclusion, our study demonstrated that treatment with JTKY ameliorated poly(I:C)-induced pneumonia. The mechanism of action of JTKY may be associated with the inhibition of the inflammatory response, the reduction of oxidative stress, and the regulation of the synthesis and degradation of ketone bodies, TCA cycle, and metabolism of alanine, aspartate, glutamate, and butanoate processes in lung.

7.
J Virol ; : e0124522, 2022 Dec 05.
Article in English | MEDLINE | ID: covidwho-2152892

ABSTRACT

The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus in vitro. It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice in vivo. Therefore, SRT shows promise as a treatment option for COVID-19. IMPORTANCE The study shows SRT is an effective entry inhibitor against infection of SARS-CoV-2, which is currently prevalent globally. SRT targets the S protein of SARS-CoV-2 and is effective against a panel of SARS-CoV-2 variants. It also could be used in combination to prevent SARS-CoV-2 infection. More importantly, with long history of clinical use and proven safety, SRT might be particularly suitable to treat infection of SARS-CoV-2 in the central nervous system and optimized for treatment in older people, pregnant women, and COVID-19 patients with heart complications, which are associated with severity and mortality of COVID-19.

8.
Frontiers in pharmacology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2033862

ABSTRACT

Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice;the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory effects of JTKY in poly(I:C)-induced pneumonia model mice were studied using untargeted metabolomics. Our results showed that JTKY treatment decreased the wet-to-dry ratio in the lung tissue, total protein concentration, and total cell count of the bronchoalveolar lavage fluid (BALF). Hematoxylin and Eosin (HE) and Masson staining indicated that the JTKY treatment alleviated the pathological changes and decreased the fibrotic contents in the lungs. JTKY treatment also decreased the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α)] and increased the levels of immunomodulatory cytokines (IL-4 and IL-10) in the BALF and serum. Flow cytometry analysis showed that the JTKY treatment lowered the ratio of CD86+/CD206+ macrophages in the BALF, decreased inducible nitric oxide synthase (iNOS) level, and increased arginase 1 (Arg-1) level in lung. JTKY also lowered CD11b+Ly6G+ neutrophils in BALF and decreased myeloperoxidase (MPO) activity in lung. Moreover, it also elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) level in lung. Untargeted metabolomic analysis showed that the JTKY treatment could affect 19 metabolites in lung, such as L-adrenaline, L-asparagine, ornithine, and alpha-ketoglutaric acid. These metabolites are associated with the synthesis and degradation of ketone bodies, butanoate, alanine, aspartate, and glutamate metabolism, and tricarboxylic acid (TCA) cycle processes. In conclusion, our study demonstrated that treatment with JTKY ameliorated poly(I:C)-induced pneumonia. The mechanism of action of JTKY may be associated with the inhibition of the inflammatory response, the reduction of oxidative stress, and the regulation of the synthesis and degradation of ketone bodies, TCA cycle, and metabolism of alanine, aspartate, glutamate, and butanoate processes in lung.

9.
Front Cell Dev Biol ; 10: 896618, 2022.
Article in English | MEDLINE | ID: covidwho-1847154
10.
Autophagy ; 18(11): 2576-2592, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1722064

ABSTRACT

SARS-CoV-2 infections have resulted in a very large number of severe cases of COVID-19 and deaths worldwide. However, knowledge of SARS-CoV-2 infection, pathogenesis and therapy remains limited, emphasizing the urgent need for fundamental studies and drug development. Studies have shown that induction of macroautophagy/autophagy and hijacking of the autophagic machinery are essential for the infection and replication of SARS-CoV-2; however, the mechanism of this manipulation and the function of autophagy during SARS-CoV-2 infection remain unclear. In the present study, we identified ORF3a as an inducer of autophagy (in particular reticulophagy) and revealed that ORF3a localizes to the ER and induces RETREG1/FAM134B-related reticulophagy through the HMGB1-BECN1 (beclin 1) pathway. As a consequence, ORF3a induces ER stress and inflammatory responses through reticulophagy and then sensitizes cells to the acquisition of an ER stress-related early apoptotic phenotype and facilitates SARS-CoV-2 infection, suggesting that SARS-CoV-2 ORF3a hijacks reticulophagy and then disrupts ER homeostasis to induce ER stress and inflammatory responses during SARS-CoV-2 infection. These findings reveal the sequential induction of reticulophagy, ER stress and acute inflammatory responses during SARS-CoV-2 infection and imply the therapeutic potential of reticulophagy and ER stress-related drugs for COVID-19.Abbreviations: CQ: chloroquine; DEGs: differentially expressed genes; ER: endoplasmic reticulum; GSEA: gene set enrichment analysis; HMGB1: high mobility group box 1; HMOX1: heme oxygenase 1; MERS-CoV: Middle East respiratory syndrome coronavirus; RETREG1/FAM134B: reticulophagy regulator 1; RTN4: reticulon 4; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TN: tunicamycin.


Subject(s)
Autophagy , COVID-19 , Viroporin Proteins , Humans , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Stress , HMGB1 Protein/metabolism , SARS-CoV-2 , Viroporin Proteins/metabolism
11.
Clin Pharmacol Ther ; 112(5): 990-999, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1694806

ABSTRACT

As the scientific research community along with healthcare professionals and decision makers around the world fight tirelessly against the coronavirus disease 2019 (COVID-19) pandemic, the need for comparative effectiveness research (CER) on preventive and therapeutic interventions for COVID-19 is immense. Randomized controlled trials markedly under-represent the frail and complex patients seen in routine care, and they do not typically have data on long-term treatment effects. The increasing availability of electronic health records (EHRs) for clinical research offers the opportunity to generate timely real-world evidence reflective of routine care for optimal management of COVID-19. However, there are many potential threats to the validity of CER based on EHR data that are not originally generated for research purposes. To ensure unbiased and robust results, we need high-quality healthcare databases, rigorous study designs, and proper implementation of appropriate statistical methods. We aimed to describe opportunities and challenges in EHR-based CER for COVID-19-related questions and to introduce best practices in pharmacoepidemiology to minimize potential biases. We structured our discussion into the following topics: (1) study population identification based on exposure status; (2) ascertainment of outcomes; (3) common biases and potential solutions; and (iv) data operational challenges specific to COVID-19 CER using EHRs. We provide structured guidance for the proper conduct and appraisal of drug and vaccine effectiveness and safety research using EHR data for the pandemic. This paper is endorsed by the International Society for Pharmacoepidemiology (ISPE).


Subject(s)
COVID-19 , Comparative Effectiveness Research , Humans , Comparative Effectiveness Research/methods , Electronic Health Records , Pharmacoepidemiology , Pandemics/prevention & control
12.
Anat Rec (Hoboken) ; 304(11): 2566-2578, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1460147

ABSTRACT

COVID-19 (coronavirus) has spread all over the world with a high infection rate. Currently, there are no targeted therapeutic drugs for COVID-19 as well as for stress induced by COVID-19. The unpredictable events of COVID-19 can trigger feelings of fear, worry, or unease in people, leading to stress-related disorders such as depression and anxiety. It has been reported that individuals, including COVID-19 patients, medical staff, and ordinary people, are under both physical and psychological pressure, and many of them have developed depression or anxiety during this pandemic. Traditional Chinese medicine (TCM) has been widely used in treating depression with relatively better safety and efficacy and may have an important role in treating stress-related disorders induced by COVID-19. In this review, we collected the common TCM treatment methods including Qigong, Acupuncture, Five Elements Musical Therapy, Five Elements Emotional Therapy, and Chinese herbal medicine from the databases of PubMed and the China National Knowledge Internet to illustrate the effect of TCM on depression. The better knowledge of TCM and implementation of TCM in COVID-19 clinics may help to effectively improve depression induced by COVID-19, may assist people to maintain a healthy physical and mental quality, and may alleviate the current shortage of medical resources.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Depression/epidemiology , Depression/therapy , Medicine, Chinese Traditional/methods , Acupuncture Therapy/methods , Drugs, Chinese Herbal/therapeutic use , Humans , Qigong/methods , Treatment Outcome
13.
ISPRS International Journal of Geo-Information ; 10(9):627, 2021.
Article in English | MDPI | ID: covidwho-1430889

ABSTRACT

The Coronavirus disease 2019 (COVID-19) has been spreading in New York State since March 2020, posing health and socioeconomic threats to many areas. Statistics of daily confirmed cases and deaths in New York State have been growing and declining amid changing policies and environmental factors. Based on the county-level COVID-19 cases and environmental factors in the state from March to December 2020, this study investigates spatiotemporal clustering patterns using spatial autocorrelation and space-time scan analysis. Environmental factors influencing the COVID-19 spread were analyzed based on the Geodetector model. Infection clusters first appeared in southern New York State and then moved to the central western parts as the epidemic developed. The statistical results of space-time scan analysis are consistent with those of spatial autocorrelation analysis. The analysis results of Geodetector showed that both temperature and population density were strong indications of the monthly incidence of COVID-19, especially in March and April 2020. There is a trend of increasing interactions between various risk factors. This study explores the spatiotemporal pattern of COVID-19 in New York State over ten months and explains the relationship between the disease transmission and influencing factors.

14.
Front Psychiatry ; 12: 696823, 2021.
Article in English | MEDLINE | ID: covidwho-1295708

ABSTRACT

When a biological public health event breaks out, due to the characteristics of their work, doctors and nurses must face risks directly when the situation is unknown. Their difficulties and psychological pressure are unimaginable. However, few studies have investigated the difficulties encountered by those doctors and nurses and their requirements for psychological interventions. This study aimed to explore the difficulties and psychological intervention needs of doctors and nurses during the new biological public health events in China in 2019. We carried out a qualitative study using a phenomenological approach. We used convenience sampling to identify participants who provided direct care and treatment for patients with biological events such as coronavirus disease 2019 (COVID-19). They participated in semi-structured, in-depth face-to-face interviews. The interviews were transcribed and analyzed using Colaizzi's seven-step method. Analysis of this study was divided into the difficulties encountered by doctors and nurses and their mental health need. The difficulties encountered by doctors and nurses included four themes: being worried about the impact on others, lack of knowledge and skills, difficult patients, being socially isolated, and the feeling of uncertainty. The mental health need was summarized into two parts, needs expressed by doctors and nurses and needs observed by researchers. Doctors and nurses mostly did not feel that they needed any psychological support, but the researchers noticed several signs of stress or potential mental health problems among interviewees. Doctors and nurses faced significant complex and multidimensional difficulties. Many denied needing psychological support, even though the researchers noted signs that it might be helpful. Interventions and support strategies that involve mental health promotion activities should consider individual needs related to doctors and nurses' situation.

15.
Front Genet ; 12: 663098, 2021.
Article in English | MEDLINE | ID: covidwho-1268247

ABSTRACT

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.

16.
BMC Nephrol ; 21(1): 504, 2020 11 24.
Article in English | MEDLINE | ID: covidwho-975879

ABSTRACT

BACKGROUND: Since the Coronavirus Disease 2019 (COVID-19) outbreak, there is accumulating data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. Postmortem investigations reveal renal involvement in COVID-19, and most recently, several biopsy researches reveal that acute tubular injury, as well as glomerular nephropathy such as collapsing glomerulopathy were common histological findings. However, to our best knowledge, there is limited data regarding IgA nephropathy in the setting of COVID-19. CASE PRESENTATION: In the present case, we report a 65-year old Chinese woman who presented with dark-colored urine, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient's underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up. CONCLUSIONS: It is important to consider the underlying glomerular disease exacerbation as well as virus induced injury when dealing with renal abnormalities in patients with COVID-19. A kidney biopsy may be indicated to exclude a rapidly progressive glomerular disease.


Subject(s)
COVID-19/diagnostic imaging , Glomerulonephritis, IGA/pathology , Kidney/pathology , Lung/diagnostic imaging , Aged , Angiotensin Receptor Antagonists/therapeutic use , COVID-19/complications , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19 Nucleic Acid Testing , Disease Progression , Female , Glomerular Filtration Rate , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/metabolism , Glomerulonephritis, IGA/physiopathology , Glucocorticoids/therapeutic use , Hematuria/physiopathology , Humans , Kidney/ultrastructure , Kidney/virology , Microscopy, Electron , Proteinuria/physiopathology , Recovery of Function
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