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1.
Natl Sci Rev ; 10(5): nwac034, 2023 May.
Article in English | MEDLINE | ID: covidwho-2311829

ABSTRACT

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

2.
Animal Model Exp Med ; 3(1): 93-97, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-2288057

ABSTRACT

BACKGROUND: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models. METHODS: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response. RESULTS: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. CONCLUSION: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

3.
Poult Sci ; 102(4): 102501, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2287484

ABSTRACT

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.


Subject(s)
Coronavirus Infections , Infectious bronchitis virus , Poultry Diseases , Viral Vaccines , Animals , Chickens , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Poultry Diseases/prevention & control , Vaccine Efficacy , Vaccines, Attenuated/administration & dosage , Viral Vaccines/administration & dosage , Age Factors
4.
Drugs Today (Barc) ; 59(1): 37-49, 2023 Jan.
Article in English | MEDLINE | ID: covidwho-2269398

ABSTRACT

On March 23, 2022, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have highly expressed prostate-specific membrane antigen (PSMA) and have at least one metastatic lesion. It is the first FDA-approved targeted radioligand therapy for eligible men with PSMA-positive mCRPC. Lutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation, resulting in DNA damage and cell death. PSMA is overexpressed in cancer cells while being lowly expressed in normal tissues, which makes it an ideal theranostic target. As precision medicine advances, this is a thrilling turning point for highly individualized treatments. This review aims to summarize the pharmacology and clinical studies of the novel drug lutetium Lu 177 vipivotide tetraxetan for the treatment of mCRPC, emphasizing its mechanism of action, pharmacokinetics and safety.


Subject(s)
Lutetium , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Lutetium/adverse effects , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostate-Specific Antigen/therapeutic use , Treatment Outcome
5.
Pathogens ; 11(12)2022 Dec 17.
Article in English | MEDLINE | ID: covidwho-2163548

ABSTRACT

Porcine epidemic diarrhea virus (PEDV), a highly pathogenic enteric coronavirus, is regarded as one of the most severe porcine pathogens. To date, there are still no commercial vaccines or drugs that can provide full protection against the epidemic strains. A better understanding of the subcellular location of individual proteins could benefit from studying the protein functions and mechanisms of how the virus regulates key cellular processes, finally leading to the development of antiviral agents. In this study, we characterized the subcellular localization of PEDV proteins using multi-labeled fluorescent immunocytochemistry. As a result, 11 proteins showed cytoplasmic distribution and 10 proteins showed both cytoplasmic and nuclear distribution. Furthermore, we demonstrated that four proteins (Nsp3, Nsp4, Nsp6, and S1) were co-localized in the endoplasmic reticulum (ER), while four proteins (Nsp2, S2, N, and ORF3) were partially observed in the ER, two proteins (E and M) were co-localized in the Golgi apparatus, and two proteins (Nsp2 and E) were partially co-localized with the mitochondria. These viral proteins may perform specific functions at specific cellular locations. Together, these results describe a subcellular localization map of PEDV proteins, which will help to characterize the functions of these proteins in the future.

6.
Eur J Pediatr Surg ; 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2118065

ABSTRACT

INTRODUCTION: Since the onset of coronavirus disease 2019 (COVID-19), stay-at-home orders and fear caused by the pandemic have had a significant effect on the timing and outcomes of testicular torsion. However, the evidence was limited since the study results were inconsistent. This study aims to examine the hospitalization rates, timing, and outcomes of testicular torsion in children before and during the pandemic. MATERIALS AND METHODS: Using PubMed, Embase, and Google Scholar databases, we conducted a systematic search and meta-analysis of studies reporting the timing and outcomes of children admitted with testicular torsion before and during the COVID-19 pandemic. Subgroup analyses were conducted to explore possible sources of heterogeneity. RESULT: The outcomes of 899 testicular torsion patients from eight studies were evaluated. Our study found an increased hospitalization rate for patients with testicular torsion (incidence rate ratio = 1.60, 95% confidence interval [CI]: 1.27-2.03; p = 0.001). Despite a significant increase in the duration of symptoms during the COVID-19 pandemic (weighted mean difference = 11.04, 95% CI: 2.75-19.33; p = 0.009), orchiectomy rates did not increase (odds ratio = 1.33, 95% CI: 0.85-2.10; p = 0.147). CONCLUSION: During the COVID-19 pandemic, hospitalization rates for testicular torsion and the duration of symptoms among children increased significantly. Moreover, the rate of orchiectomy did not increase during the pandemic, indicating that pediatric emergency services have remained efficient and have prevented an increase in the number of orchiectomies performed despite pandemic-related closures and delays in transporting patients to medical care.

7.
Dis Markers ; 2022: 7099908, 2022.
Article in English | MEDLINE | ID: covidwho-2053426

ABSTRACT

Objective: This research sets out to elucidate the influence of evidence-based nursing (EBN) on psychological status (PSY), neurological function, and quality of life (QoL) of patients with acute poststroke depression (PSD). Methods: One hundred and fifty stroke patients who received treatment in the Characteristic Medical Center of PLA Rocket Force between December 2019 and December 2021 were enrolled, including 100 cases (Group A) treated with comprehensive EBN and 50 patients (Group B) with routine nursing. Anxiety and depression (Self-Rating Anxiety Scale [SAS] and Self-Rating Depression Scale [SDS] scores), neurological function (National Institutes of Health Stroke Scale [NIHSS] and Scandinavian Stroke Scale [SSS] scores), QoL (Generic Quality Of Life Inventory-74 [GQOLI-74] score), and complication rate of both groups were evaluated, as well as total effective rate and nursing satisfaction. Results: Group A outperformed Group B with lower scores of NIHSS, SSS, SAS, and SDS and higher GOOLI-74 scores. Besides, lower complication rate and higher total effective rate and nursing satisfaction were determined in Group A. Conclusions: EBN can better improve the PSY of patients with acute PSD, restore their neurological function, and effectively improve their QoL.


Subject(s)
Depression , Stroke , Depression/etiology , Evidence-Based Nursing , Humans , Polyesters , Quality of Life/psychology , Stroke/complications
8.
Curr Med Sci ; 42(4): 885-894, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1959093

ABSTRACT

OBJECTIVE: This study aimed to investigate whether perceived stress mediated the relationship between hope and anxiety/depression symptoms among patients with COVID-19 during the epidemic. In addition, the potential moderating effect of coping styles was examined. METHODS: From February 26 to March 10, 2020, patients with COVID-19 were asked to complete a questionnaire online, which included demographic characteristics, as well as the SCL-90-Anxiety, SCL-90-Depression, Chinese Perceived Stress Scale (CPSS), Herth Hope Index (HHI), and Trait Coping Style Questionnaire (TCSQ). Hierarchical linear regression was performed to explore independent factors of anxiety/depression. A multi-group structural equation modeling with the collected data from patients in the Negative Coping style (NC) group and Positive Coping style (PC) group was used to test the hypothesized mechanism. RESULTS: In total, 382 valid questionnaires of patients were obtained, including 96 from NC patients and 286 from PC patients. In the hierarchical linear regression, hope and perceived stress were independent risk factors for both anxiety and depression in the total sample and PC group. However, hope was not independently related to anxiety/depression in the NC group. As hypothesized, the hope of patients had significant and negative indirect effects on both anxiety and depression that were mediated by perceived stress, However, the direct effect from stress on anxiety and depression was stronger for NC patients than for PC patients. Besides, hope had significant direct effects on anxiety/depression in PC patients, but not in NC patients. CONCLUSION: During the COVID-19 epidemic, perceived stress could mediate the relationship between hope and anxiety/depression symptoms among COVID-19 patients, with coping style moderating this cultivation process.


Subject(s)
COVID-19 , Depression , Adaptation, Psychological , Anxiety/epidemiology , Anxiety/etiology , COVID-19/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression/etiology , Humans , Stress, Psychological/etiology
10.
Annals of Tourism Research ; 94(75), 2022.
Article in English | CAB Abstracts | ID: covidwho-1889197

ABSTRACT

This paper examines the influence of mortality salience on preference for humanoid robot service. Six studies confirm that consumers/tourists are reluctant to adopt humanoid (vs. non-humanoid) service robots and robotic services when mortality is salient. The effect is driven by the perceived threat to human identity. However, temporal distance can alleviate the mortality salience effect. Eliciting a distant-future temporal perspective can reduce consumers'/tourists' existential anxiety, and then attenuate negative reactions to humanoid service robots. This research provides an innovative standpoint on consumers' reactions to service robots under conditions of mortality salience (e.g., during the COVID-19 pandemic). It also offers insight into service robot implementation and design in the hospitality and tourism industry.

11.
Front Pharmacol ; 13: 879733, 2022.
Article in English | MEDLINE | ID: covidwho-1862647

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus (α-CoV) that causes high mortality in suckling piglets, leading to severe economic losses worldwide. No effective vaccine or commercial antiviral drug is readily available. Several replicative enzymes are responsible for coronavirus replication. In this study, the potential candidates targeting replicative enzymes (PLP2, 3CLpro, RdRp, NTPase, and NendoU) were screened from 187,119 compounds in ZINC natural products library, and seven compounds had high binding potential to NTPase and showed drug-like property. Among them, ZINC12899676 was identified to significantly inhibit the NTPase activity of PEDV by targeting its active pocket and causing its conformational change, and ZINC12899676 significantly inhibited PEDV replication in IPEC-J2 cells. It first demonstrated that ZINC12899676 inhibits PEDV replication by targeting NTPase, and then, NTPase may serve as a novel target for anti-PEDV.

13.
Annals of Tourism Research ; 94:103383, 2022.
Article in English | ScienceDirect | ID: covidwho-1748288

ABSTRACT

This paper examines the influence of mortality salience on preference for humanoid robot service. Six studies confirm that consumers/tourists are reluctant to adopt humanoid (vs. non-humanoid) service robots and robotic services when mortality is salient. The effect is driven by the perceived threat to human identity. However, temporal distance can alleviate the mortality salience effect. Eliciting a distant-future temporal perspective can reduce consumers'/tourists' existential anxiety, and then attenuate negative reactions to humanoid service robots. This research provides an innovative standpoint on consumers' reactions to service robots under conditions of mortality salience (e.g., during the COVID-19 pandemic). It also offers insight into service robot implementation and design in the hospitality and tourism industry.

14.
Infect Dis Poverty ; 10(1): 140, 2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1639437

ABSTRACT

BACKGROUND: Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. METHODS: We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (Reff) was used to estimate the transmission interaction in different age groups. RESULTS: A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (Reff = 4.28), followed by group 2 to 3 (Reff = 2.61), and group 2 to 4 (Reff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45-64 years old. CONCLUSIONS: Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15-64 years should first be vaccinated to prevent transmission in China.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , China , Cities , Humans , Middle Aged , SARS-CoV-2 , Vaccination , Young Adult
15.
J Cardiovasc Transl Res ; 15(1): 38-48, 2022 02.
Article in English | MEDLINE | ID: covidwho-1594479

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.


Subject(s)
COVID-19 , Hypertension , Animals , Humans , Hypertension/complications , Hypertension/drug therapy , Inpatients , Mice , Mice, Transgenic , Renin-Angiotensin System , SARS-CoV-2 , Virulence
16.
Ecotoxicol Environ Saf ; 228: 112989, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1517133

ABSTRACT

Ficus hirta Vahl. has been reported to have hepatoprotective, antitumor, antibacterial functions, and is used to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ammonia nitrogen is one of the most common environmental stress factors in aquaculture. Long-term exposure to high concentrations of ammonia nitrogen can induce oxidative stress and increase the risk of infections. However, whether Ficus hirta Vahl. has effect on ammonia nitrogen stress is unclear. In present study we report that Ficus hirta Vahl. improves the activity of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) of shrimp and decreases shrimp mortality caused by ammonia nitrogen stress. It is demonstrated that miR-2765 is negatively regulate the antioxidant capacity. We find that SOD was a direct target gene of miR-2765. MiR-2765 can bind to 3'-untranslated region (3'-UTR) of SOD to inhibit its transcription. Furthermore, Ficus hirta Vahl. down-regulates miR-2765 to activate the antioxidant capacity to alleviate the damage caused by ammonia nitrogen stress. Interestingly, overexpression of miR-2765 could attenuate the protective effect of Ficus hirta Vahl. on shrimp under ammonia nitrogen stress. These data indicate that Ficus hirta Vahl. alleviates the damage of ammonia nitrogen stress in shrimp by repressing miR-2765 and activating the antioxidant enzyme system. This study will provide a theoretical basis and a new perspective for assessing the toxicity mechanism of ammonia nitrogen in the process of farming on shrimp.

17.
J Hepatol ; 75(2): 439-441, 2021 08.
Article in English | MEDLINE | ID: covidwho-1454288

ABSTRACT

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 , Immunogenicity, Vaccine/immunology , Non-alcoholic Fatty Liver Disease , Vaccination , Vaccines, Inactivated , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , China/epidemiology , Female , Humans , Male , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Outcome Assessment, Health Care , SARS-CoV-2/immunology , Vaccination/adverse effects , Vaccination/methods , Vaccination/statistics & numerical data , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects
18.
Ital J Pediatr ; 47(1): 142, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1286831

ABSTRACT

OBJECTIVE: To control the transmission of coronavirus disease 2019 (COVID-19), the Chinese government encouraged people to stay at home. This study aimed to evaluate the effects of home confinement on the occurrence of fractures among children. STUDY DESIGN: We retrospectively reviewed children admitted to Children's Hospital of Chongqing Medical University, for traumatic injury from January 24 to March 10, 2020, and the same time period in 2017, 2018 and 2019. At the same time, children with fracture were screened out and the date for the past 4 years was compared in terms of etiology, location of fracture, sex and age to evaluate the effects of home confinement on the epidemiology of pediatric fractures during the COVID-19 outbreak. RESULTS: There were 6066 fractures in5,346 patients in 2017-2019, and 1034 fractures in 862 patients in 2020; the number of patients in all years reached a peak at the age of 2 to 4 years. The patients were slightly younger in 2020 than in 2017-2019 (t = 9.953, 95% CI: 0.846-1.262), and the proportion of boys in 2017-2019 is higher than in 2020 (X2 = 6.944, P = 0.008). Home confinement and traffic restriction resulted in a reduction in traffic accidents-associated fractures among children (X2 = 16.399, P < 0.001). CONCLUSION: Home confinement lead to the significant reduction in the number of pediatric fractures, especially in male children, but the number of patients under 4 years old was still considerable, and the proportion of younger patients even increased. Therefore, the perspective of children should not be relaxed during home isolation.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Fractures, Bone/epidemiology , Physical Distancing , Adolescent , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Pandemics , Retrospective Studies , SARS-CoV-2
19.
Front Pharmacol ; 12: 673485, 2021.
Article in English | MEDLINE | ID: covidwho-1282402

ABSTRACT

Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drugs combinations on inflammatory cytokine production, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.

20.
Infect Dis Poverty ; 10(1): 53, 2021 Apr 19.
Article in English | MEDLINE | ID: covidwho-1191906

ABSTRACT

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Although public health countermeasures effectively controlled the epidemic in China, non-pharmaceutical interventions can neither be maintained indefinitely nor conveniently implemented globally. Vaccination is mainly used to prevent COVID-19, and most current antiviral treatment evaluations focus on clinical efficacy. Therefore, we conducted population-based simulations to assess antiviral treatment effectiveness among different age groups based on its clinical efficacy. METHODS: We collected COVID-19 data of Wuhan City from published literature and established a database (from 2 December 2019 to 16 March 2020). We developed an age-specific model to evaluate the effectiveness of antiviral treatment in patients with COVID-19. Efficacy was divided into three types: (1) viral activity reduction, reflected as transmission rate decrease [reduction was set as v (0-0.8) to simulate hypothetical antiviral treatments]; (2) reduction in the duration time from symptom onset to patient recovery/removal, reflected as a 1/γ decrease (reduction was set as 1-3 days to simulate hypothetical or real-life antiviral treatments, and the time of asymptomatic was reduced by the same proportion); (3) fatality rate reduction in severely ill patients (fc) [reduction (z) was set as 0.3 to simulate real-life antiviral treatments]. The population was divided into four age groups (groups 1, 2, 3 and 4), which included those aged ≤ 14; 15-44; 45-64; and ≥ 65 years, respectively. Evaluation indices were based on outbreak duration, cumulative number of cases, total attack rate (TAR), peak date, number of peak cases, and case fatality rate (f). RESULTS: Comparing the simulation results of combination and single medication therapy s, all four age groups showed better results with combination medication. When 1/γ = 2 and v = 0.4, age group 2 had the highest TAR reduction rate (98.48%, 56.01-0.85%). When 1/γ = 2, z = 0.3, and v = 0.1, age group 1 had the highest reduction rate of f (83.08%, 0.71-0.12%). CONCLUSIONS: Antiviral treatments are more effective in COVID-19 transmission control than in mortality reduction. Overall, antiviral treatments were more effective in younger age groups, while older age groups showed higher COVID-19 prevalence and mortality. Therefore, physicians should pay more attention to prevention of viral spread and patients deaths when providing antiviral treatments to patients of older age groups.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/prevention & control , SARS-CoV-2/drug effects , Adolescent , Age Factors , Aged , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Humans , Infectious Disease Incubation Period , Middle Aged , Models, Statistical , Young Adult
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