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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323568

ABSTRACT

Background: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. Methods: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. Results: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). Conclusions: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319516

ABSTRACT

Objective: Novel coronavirus (nCoV, SARS-CoV-2) infection becomes a world-wide epidemic which has complicated and diversified symptoms, but no special treatment. In this study, diagnosis and treatment of family clustering nCoV infection were analyzed. Methods: : The Sichuan Suining Central Hospital received 11 patients with confirmed nCoV virus infection from 4 families during January 23 rd , 2020 to February 20 th , 2020. Their clinical symptoms, treatment conditions and changes of disease state were reviewed in the present study. Results: In all 4 families, there were 1-2 members in each family who had contact with epidemic disease. Clinical manifestations were: 3 cases had debilitation only, 1 case had cough only, 1 case had diarrhea (a child patient of four years old), 5 cases had fever and cough, and 1 case had blood-stained sputum. According to image changes, no image change was observed in 1 child patient. Multiple focal ground-glass opacities were detected from 2 patients and multiple patchy shadows were observed from 8 patients, especially in lung periphery. Complications with basic diseases: there were hypertension in 3 cases, diabetes in 2 cases, and hypertension and diabetes in 1 case. Moreover, there’s one patient who had rheumatic heart disease and received mitral and aortic valve replacement 2 years ago. There’s another one who had depression and suicidal tendency. All 11 cases divided into mild type (1 child patient), moderate type (8 patients), severe type (1 patient) and critical type (1 patient). Treatment: the mild child patient (4 years old) was administrated with 2.75ml lopinavir / ritonavir oral liquid (twice per day) and intravenous drip of 0.17g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h for one week. Meanwhile, the child was asked to take azithromycin orally. 7 moderate patients were treated with intravenous drip of 0.5g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h (twice per day) and two pieces of lopinavir/ritonavior (twice per day) for 7-10 days. In the same time, patients were given with reasonable amount of antibiotics by oral or intravenous drip. 1 severe patient and 1 critical patent were treated with 5,000,000 U recombinant human interferon α2b injection (3,000,000 U/pc) and aerosol inhalation of 2ml sterile water for injection (5ml*50 pcs/ box), twice per day. Besides, they took 2 pieces of lopinavir/ritonavior, twice per day. The whole treatment program lasted for 6-12 days, accompanied with appropriate amount of intravenous drip of antibiotics. The critical patient was also provided with mechanical ventilation. During the treatment, severe and critical patients were treated by resochin for 4-5 days for evident respiratory symptoms. One moderate patient was treated with 2 pieces of lopinavir/ritonavior, twice per day. In the same time, it was administrated by intravenous drip of antibiotics. However, resochin treatment was applied for positive novel coronavirus nucleic acid of respiratory sputum specimen after 11 days of treatment. Discharge: After treatment, patients with body temperatures of all patients recovered to normal level, and respiratory symptoms and digestive tract symptoms relieved significantly, significant coefficient of exudative lesion at lung according to chest CT and negative novel coronavirus nucleic acid of continuous two respiratory sputum specimens (sampling interval was at least 1 day) were allowed to be discharged. Adverse reactions: 4 patients had loose stools and abdominal discomfort, and another 2 cases had diarrhea. Conclusions: : SARS-CoV-2 infection have complicated and diversified symptoms, which shall be identified according to epidemic history and novel coronavirus nucleic acid test. In particular, the whole family in which there’s a patient with confirmed SARS-CoV-2 shall be isolated for screening in addition to the patient. The lopinavir/ritonavior administration combined with ribavirin or recombinant Human Interferon (RHI) α2b is effective, accompanied with mild adverse reaction. If lopinavir/ritonavior administration and / or combined with ribavirin and RHI α2b is invalid, adding resochin might be effective.

4.
Chin Med J (Engl) ; 134(20): 2438-2446, 2021 Oct 07.
Article in English | MEDLINE | ID: covidwho-1462529

ABSTRACT

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19. METHODS: Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders. RESULTS: The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. CONCLUSIONS: Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.


Subject(s)
COVID-19 , China/epidemiology , Cities , Humans , SARS-CoV-2
5.
Science ; 371(6536): 1374-1378, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1255508

ABSTRACT

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/pathology , COVID-19/virology , Cell Line , Cell Survival/drug effects , Chemokine CXCL10/metabolism , Disease Models, Animal , Drug Design , Humans , Interferon-beta/metabolism , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Oligopeptides , Proline/analogs & derivatives , Protease Inhibitors/chemistry , Protease Inhibitors/therapeutic use , Protease Inhibitors/toxicity , Rats , Rats, Sprague-Dawley , Viral Load/drug effects , Virus Replication
6.
BMC Infect Dis ; 21(1): 206, 2021 Feb 24.
Article in English | MEDLINE | ID: covidwho-1102331

ABSTRACT

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Adult , Aged , COVID-19/virology , China/epidemiology , Comorbidity , Female , Humans , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Virus Shedding
9.
Ann Med ; 52(7): 361-366, 2020 11.
Article in English | MEDLINE | ID: covidwho-679531

ABSTRACT

BACKGROUND: Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19. METHODS: This is a retrospective multi-centre study involving patients admitted between January 16th and March 10th 2020. The composite endpoint was defined as the presence of at least one of the following, intensive care unit (ICU) admission, or the need for mechanical ventilation, or death. RESULTS: A total of 472 consecutive cases admitted to 51 certified COVID-19 tertiary care hospitals were enrolled (median age was 43 [32-53.5] years and 53.0% were male). There were 101 (21.4%) patients presented with comorbidities, including hypertension (15.0%), diabetes mellitus (7.8%), coronary artery disease (2.6%), chronic obstructive pulmonary disease (1.3%) and cerebrovascular disease (1.9%). The composite endpoint occurred in 65 (13.8%) patients. Multivariate stepwise logistic regression analysis indicated that older age (odds ratio [OR] 1.39, 95% confidence interval (CI) 1.05-1.85, per 10-year increment), antecedent hypertension (OR 2.82, 95% CI 1.09-7.29), neutrophil counts (OR 1.33, 95% CI 1.14-1.56) and lactate dehydrogenase level (OR 1.01, 95% CI 1.00-1.01) were independently associated with the presence of composite endpoint. Hypertensive patients, compared with controls, had a greater chance of experiencing the composite endpoint (p < .001) and each individual endpoint, i.e. ICU admission (p < .001), mechanical ventilation (p < .001) and death (p = .012). In the stepwise regression analysis of anti-hypertensive medications, none of the therapy predicted the composite endpoint. CONCLUSIONS: Hypertension is a common comorbidity in patients with COVID-19 and associated with adverse outcomes. KEY MESSAGES Hypertension was identified as the comorbidity associated with the prognosis of COVID-19 in this retrospective cohort. Patients with hypertension could experience an increased risk of the composite endpoint. Anti-hypertensive therapy did not affect patient outcomes.


Subject(s)
Coronavirus Infections/epidemiology , Hospitalization/statistics & numerical data , Hypertension/epidemiology , Intensive Care Units/statistics & numerical data , Pneumonia, Viral/epidemiology , Adult , Aged , Antihypertensive Agents/administration & dosage , COVID-19 , Cohort Studies , Comorbidity , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , Pandemics , Prognosis , Retrospective Studies , Risk Factors
10.
Heart ; 106(15): 1154-1159, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-155332

ABSTRACT

OBJECTIVE: We sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with COVID-19 in a region of China where medical resources are less stressed than in Wuhan (the epicentre of the pandemic). METHODS: We prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit. RESULTS: A total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34-62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p<0.001) and treatment with vasoactive agents (31.2% vs 0%, p<0.001). Log hs-TnT was associated with disease severity (OR 6.63, 95% CI 2.24 to 19.65), and all of the three deaths occurred in patients with acute myocardial injury. CONCLUSION: Acute myocardial injury is common in patients with COVID-19 and is associated with adverse prognosis.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Troponin T/blood , Adult , Age Factors , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19 , Cardiovascular Agents/therapeutic use , China/epidemiology , Cohort Studies , Glomerular Filtration Rate , Humans , Intensive Care Units/statistics & numerical data , Middle Aged , Natriuretic Peptide, Brain/blood , Pandemics , Peptide Fragments/blood , Prognosis , SARS-CoV-2 , Severity of Illness Index
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