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1.
J Cardiovasc Transl Res ; 2022 Jan 01.
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.

2.
Infect Dis Poverty ; 10(1): 140, 2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1582000

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
3.
Preprint in English | EuropePMC | ID: ppcovidwho-296434

ABSTRACT

Background: The onset of various kidney diseases have been reported after COVID-19 vaccination. However, detailed clinical and pathological examination of kidney injury in patients receiving inactivated vaccines are lacking.<br><br>Methods: 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. We obtained samples of blood, urine, and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observation were described. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein and Nucleoprotein were stained using immune-fluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay.<br><br>Findings: The study group included 17 patients, 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 (ANCA)-associated vasculitis, anti-GBM nephritis, acute tubulointerstitial nephritis, and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and 10 (58.82%) after the second dose. We found no definitive evidence of SARS-CoV-2 Spike protein or Nucleoprotein deposition in the kidney biopsy samples. Serological 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.<br><br>Interpretation: We observed various kidney diseases following inactivated SARS-CoV-2 vaccine administration. Our findings provide an evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of inactivated SARS-CoV-2 vaccine renal safety.<br><br>Funding: This study was funded by National Natural Science Foundation of China (91742205, 82170711, 81800636, 82070733, 81625004), Clinical Medicine Plus X—Young Scholars Project of Peking University (PKU2021LCXQ017), the Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046), Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), and Beijing Young Scientist Program (BJJWZYJH01201910001006).<br><br>Declaration of Interest: The authors declare no competing interests.<br><br>Ethical Approval: This study was approved by the institutional review board of Peking University First Hospital (2021-352) and the Committee on Human Subject Research and Ethics of Yunnan University (CHSRE2021020). Written Informed Consent Form was obtained from each participant.

4.
Journal of Financial and Quantitative Analysis ; 56(7):2545, 2021.
Article in English | ProQuest Central | ID: covidwho-1527938

ABSTRACT

After fitting a topic model to 40,927 COVID-19–related paragraphs in 3,581 earnings calls over the period Jan. 22–Apr. 30, 2020, we obtain firm-level measures of exposure and response related to COVID-19 for 2,894 U.S. firms. We show that despite the large negative impact of COVID-19 on their operations, firms with a strong corporate culture outperform their peers without a strong culture. Moreover, these firms are more likely to support their community, embrace digital transformation, and develop new products than those peers. We conclude that corporate culture is an intangible asset designed to meet unforeseen contingencies as they arise.

5.
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.

6.
Preprint in English | EuropePMC | ID: ppcovidwho-292220

ABSTRACT

Purpose: Most of humeral shaft fractures in children could be treated satisfactorily by conservative treatment. This study aimed to evaluate the application value of ultrasonography in conservative treatment of humeral shaft fracture in children.Methods : We retrospectively reviewed children admitted to our hospital, for humeral shaft fracture from January 2014 to March 2018. The patients were divided into two groups: ultrasonography group and X-ray group. All patients were instructed to re-examined at 1 week, 2 weeks, 4 weeks, 12 weeks, 24 weeks and 1 year from the injury date for follow-up, and evaluated the prognosis according to the Disabilities of Arm, Shoulder and Hand (DASH) score at 12 months.Results : A total of 37 children were divided into ultrasonography group, 32 children were divided into X-ray group. There was no significant difference in prognosis between the two groups. The mean number of radiation exposures of ultrasonography group was less and ultrasonic examination found radial nerve injury, and using ultrasound reduced the chance of direct or in direct contact with infected peoples. Conclusion: Ultrasound is a non-invasive, non-radioactive test, which could decrease risk of COVID-19 infection and detect the vascular nerve injury caused by fracture. Ultrasonography may be the examination method for follow-up conservative treatment of humeral shaft fracture in children during the epidemic period.

7.
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
8.
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
9.
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.

10.
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
11.
J Pharm Biomed Anal ; 195: 113876, 2021 Feb 20.
Article in English | MEDLINE | ID: covidwho-1001609

ABSTRACT

In this study, we developed a sensitive and efficient analytical approach combining a 96-well plate-based protein precipitation strategy with ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-MS/MS) in order to assess the pharmacokinetic (PK) properties of sivelestat and its metabolite XW-IMP-A in samples of plasma from ALI/ARDS patients with SIRS. The samples were separated via gradient elution with a C18 column (Phenomenex Kinetex, C18, 2.6 µm, 100 Å, 50 × 2.1 mm) using 0.1 % formic acid aqueous solution (A) and acetonitrile-methanol (1:1, V:V) (B) as a mobile phase at a 0.6 mL/min flow rate. UPLC-MS/MS spectra were generated in positive ion mode, and multiple reaction monitoring (MRM) was used to detect the following transitions: m/z 435.1 → 360.0 for sivelestat, m/z 469.0 → 394.0 for sivelestat-IS, m/z 351.0 → 276.0 for XW-IMP-A, and m/z 384.9 → 310.0 for XW-IMP-A-IS. This assay was run for 2.5 min in total, and achieved lowest limit of quantitation values of 2.0 ng/mL and 0.5 ng/mL for sivelestat and XW-IMP-A, respectively, while remaining highly linear from 2-500 ng/mL for sivelestat (r2 ≥ 0.9900) and from 0.5-125 ng/mL for XW-IMP-A (r2 ≥ 0.9900). These validated data were consistent with US Food and Drug Administration (FDA) and European Medicines Agency (EMA) acceptance criteria. In addition, this method was successfully applied to the steady-state PK evaluation of ALI/ARDS patients with SIRS.


Subject(s)
Respiratory Distress Syndrome , Tandem Mass Spectrometry , China , Chromatography, High Pressure Liquid , Chromatography, Liquid , Glycine/analogs & derivatives , Humans , Limit of Detection , Reproducibility of Results , Sulfonamides , Systemic Inflammatory Response Syndrome
13.
NPJ Vaccines ; 6(1): 1, 2021 Jan 04.
Article in English | MEDLINE | ID: covidwho-1007626

ABSTRACT

Modified Vaccinia Ankara (MVA) was recently approved as a smallpox vaccine. Variola is transmitted by respiratory droplets and MVA immunization by skin scarification (s.s.) protected mice far more effectively against lethal respiratory challenge with vaccinia virus (VACV) than any other route of delivery, and at lower doses. Comparisons of s.s. with intradermal, subcutaneous, or intramuscular routes showed that MVAOVA s.s.-generated T cells were both more abundant and transcriptionally unique. MVAOVA s.s. produced greater numbers of lung Ova-specific CD8+ TRM and was superior in protecting mice against lethal VACVOVA respiratory challenge. Nearly as many lung TRM were generated with MVAOVA s.s. immunization compared to intra-tracheal immunization with MVAOVA and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVA s.s.-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via intra-tracheal immunization. Overall, our data suggest that heterologous MVA vectors immunized via s.s. are uniquely well-suited as vaccine vectors for respiratory pathogens, which may be relevant to COVID-19. In addition, MVA delivered via s.s. could represent a more effective dose-sparing smallpox vaccine.

14.
J Proteome Res ; 19(11): 4374-4379, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-960288

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted a large portion of the world population. From a virus genetic perspective, a recent study described what genomic data revealed about the origin and emergence of SARS-CoV-2, proposing stronger action against illegal wildlife trade. In the current "big data" era, an increasing number of large-scale, multidimensional omics data sets were publicly available. Herein, we review how human genetics tells us about the transmission, pathogenesis, susceptibility, severity, and drug prioritization of COVID-19. We further drafted a genetic roadmap of COVID-19, which was also expected to be applicable to other viruses with known receptors. Our review provides insights into the way of understanding a pandemic from a human genetic perspective.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Animals , Animals, Wild , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Genetic Predisposition to Disease , Humans , Organ Specificity , Pneumonia, Viral/drug therapy , Pneumonia, Viral/genetics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , SARS-CoV-2
15.
Shock ; 54(5): 644-651, 2020 11.
Article in English | MEDLINE | ID: covidwho-867936

ABSTRACT

INTRODUCTION: Coronavirus disease-2019 (COVID-19) outbreak has spread around the world. However, the dynamic course of critically ill COVID-19 has not been described thoroughly. PATIENTS AND METHODS: We retrospectively analyzed 195 critically ill COVID-19 patients in Hubei province, China, between January 5, 2020 and April 3, 2020. Epidemiologic data, clinical features, treatments, and outcomes were collected and analyzed. RESULTS: Most critically ill patients were older with higher Acute Physiology and Chronic Health Evaluation II scores. After critical illness onset, a total of 181 (92.8%) patients received ventilation support, of which 84 (43.1%) received noninvasive and 97 (49.7%) received invasive mechanic ventilation (IMV). Among the 97 patients with IMV, 28 (28.9%) received prone ventilation, 57 (58.8%) received neuromuscular blocked therapy, and 22 (11.3%) received tracheostomy due to prolonged ventilator use. Early hypoxemia, subsequent hypercapnia, pulmonary hypertension, and finally pulmonary fibrosis were notable in the clinical course of acute respiratory distress syndrome (ARDS). Eighty-nine (45.6%) patients presented with shock. Acute kidney injury (29.7%) and secondary infection (28.2%) were also notable. The overall mortality of critically ill patients at day 28 was 42.1%. Intensive care unit (ICU) mortality was around 33%, as 16 patients died prior to ICU admission. A low PaO2/FiO2 ratio was an independent risk factor for death. High viral load was observed in most non-survivors. CONCLUSION: ARDS and shock were notable in the critical illness of COVID-19. Ventilation support and hemodynamic support were the cornerstones for critical care. High viral load was associated with death of critically ill COVID-19 patients.


Subject(s)
Cardiovascular Agents/therapeutic use , Coronavirus Infections/therapy , Hemodynamics/drug effects , Pneumonia, Viral/therapy , Respiration, Artificial , Aged , COVID-19 , Cardiovascular Agents/adverse effects , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Critical Illness , Disease Progression , Female , Hospital Mortality , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Respiration, Artificial/adverse effects , Respiration, Artificial/mortality , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Viral Load
16.
Animal Model Exp Med ; 3(1): 93-97, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-847791

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.

17.
Nat Commun ; 11(1): 5033, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-834877

ABSTRACT

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.


Subject(s)
Coronavirus Infections/mortality , Machine Learning , Pandemics , Pneumonia, Viral/mortality , Aged , Betacoronavirus , COVID-19 , China/epidemiology , Female , Humans , Logistic Models , Male , Middle Aged , Neural Networks, Computer , Risk Assessment , SARS-CoV-2 , Support Vector Machine
18.
Preprint | SSRN | ID: ppcovidwho-777

ABSTRACT

Background: Since the end of 2019, coronavirus disease-2019 (COVID-19) outbreak spreads around the world. We aimed to share the details of critically ill patien

19.
BMJ Open ; 10(7):e035430-e035430, 2020.
Article in English | MEDLINE | ID: covidwho-662396

ABSTRACT

PURPOSE: The Shanghai Suburban Adult Cohort and Biobank (SSACB) was established to identify environmental, lifestyle and genetic risk factors for non-communicable chronic diseases (NCDs) in adults (20-74 years old) living in a suburban area of Shanghai with rapid urbanisation. PARTICIPANTS: Two of eight suburban district were purposely selected according to participant willingness, health service facilities, population, geographic region and electronic medical record system. From these suburban districts, four communities were selected based on economic level and population size. At stage three, one-third of the committees/villages were randomly selected from each community. All residents aged 20-74 years old were invited as study participants. FINDINGS TO DATE: The baseline data on demographics, lifestyle and physical health-related factors were collected using a face-to-face questionnaire interview. All participants completed physical examinations and had blood and urine tests. Blood and urine samples from these tests were stored in a biobank. From 6 April 2016 through 31 October 2017, we conducted face-to-face interviews and clinical examinations in 44 887 participants: 35 727 from Songjiang District and 9160 from Jiading District. The average age of participants was 56.4±11.2 years in Songjiang and 56.6±10.5 years in Jiading. The prevalence of hypertension, diabetes and dyslipidaemia was 34.0%, 8.2% and 11.1%, respectively. FUTURE PLANS: In-person surveys will be conducted every 5 years. For annual tracking, baseline data was linked to the local health information system, which was composed of an electronic medical record system, a chronic disease management system, a cancer registry system, an infectious disease report system and a death registry system. The data of the SSACB cohort is located in the School of Public Health, Fudan University. International and domestic collaborative research projects are encouraged and inherent in the project.

20.
Nat Commun ; 11(1): 4400, 2020 09 02.
Article in English | MEDLINE | ID: covidwho-744370

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 106 TCID50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1-7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1-7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail.


Subject(s)
Betacoronavirus/physiology , Conjunctiva/virology , Coronavirus Infections/virology , Disease Models, Animal , Pneumonia, Viral/virology , Animals , Antibodies, Viral , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/pathology , Intestine, Large/virology , Lung/pathology , Lung/virology , Macaca mulatta , Male , Nasal Cavity/virology , Pandemics , Pneumonia, Viral/pathology , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2 , Trachea/virology , Viral Load , Virus Replication
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