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1.
Int J Mol Sci ; 24(10)2023 May 11.
Article in English | MEDLINE | ID: covidwho-20244460

ABSTRACT

The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a critical role in the proteolytic processing of viral polyproteins and the dysregulation of the host immune response, providing a promising therapeutic target. Here, we report the structure-guide design of novel peptidomimetic inhibitors covalently targeting SARS-CoV-2 PLpro. The resulting inhibitors demonstrate submicromolar potency in the enzymatic assay (IC50 = 0.23 µM) and significant inhibition of SARS-CoV-2 PLpro in the HEK293T cells using a cell-based protease assay (EC50 = 3.61 µM). Moreover, an X-ray crystal structure of SARS-CoV-2 PLpro in complex with compound 2 confirms the covalent binding of the inhibitor to the catalytic residue cysteine 111 (C111) and emphasizes the importance of interactions with tyrosine 268 (Y268). Together, our findings reveal a new scaffold of SARS-CoV-2 PLpro inhibitors and provide an attractive starting point for further optimization.


Subject(s)
COVID-19 , Peptidomimetics , Humans , Peptidomimetics/pharmacology , HEK293 Cells , SARS-CoV-2 , Peptide Hydrolases , Protease Inhibitors/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry
2.
Science in One Health ; 2023.
Article in English | EuropePMC | ID: covidwho-2254549

ABSTRACT

The global pandemic caused by the coronavirus disease 2019 not only exposed the fragility of global preparedness and response to public health emergence, but also illustrated the fragmentation and gaps of research and development ecosystem. This emphasizes the need for planned actions against the potentiality of new pandemics and requires research to better understand how viruses bridge the animal/human divide making human-to-human transmission of new diseases possible. Major challenges to response to new epidemics under the current health framework reside in the so called 4-CC approach that focuses on Concept, Communication, Coherence, and Continuity. There is a need to also add a One Health perspective with emphasis on governance, surveillance, capacity building and multi-disciplinary research to achieve a holistic and better integrated system. Using a regulatory framework to equip professionals might facilitate the function of a multi-sector approach that recognizes the value of their mandates and a One Health approach in their work. Collaborative, multisectoral actions under the global regulations and guidance would make evidence-based One Health approaches sustainable and accessible to everyone.

3.
Front Pharmacol ; 14: 1085509, 2023.
Article in English | MEDLINE | ID: covidwho-2271895

ABSTRACT

Background: Acting as a viral entry for coronavirus to invade human cells, TMPRSS2 has become a target for the prevention and treatment of COVID-19 infection. Before this, TMPRSS2 has presented biological functions in cancer, but the roles remain controversial and the mechanism remains unelucidated. Some chemicals have been reported to be inhibitors of TMPRSS2 and also demonstrated other pharmacological properties. At this stage, it is important to discover more new compounds targeting TMPRSS2, especially from natural products, for the prevention and treatment of COVID-19 infection. Methods: We analyzed the correlation between TMPRSS2 expression, methylation level, overall survival rate, clinical parameters, biological process, and determined the correlation between TMPRSS2 and tumor-infiltrating lymphocytes in the tumor and adjacent normal tissue of adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively by using various types of bioinformatics approaches. Moreover, we determined the correlation between TMPRSS2 protein level and the prognosis of LUAD and LUSC cohorts by immunohistochemistry assay. Furthermore, the cancer immunome atlas (TCIA) database was used to predict the relationship between the expression of TMPRSS2 and response to programmed cell death protein 1 (PD-1) blocker immunotherapy in lung cancer patients. Finally, the putative binding site of ginsenosides bound to TMPRSS2 protein was built from homology modeling to screen high-potency TMPRSS2 inhibitors. Results: We found that TMPRSS2 recruits various types of immunocytes, including CD8+, CD4+ T cells, B cells and DCs both in LUAD and LUSC patients, and the correlation between TMPRSS2 expression and CD8+ and CD4+ T cells are stronger in LUAD rather than in LUSC, but excludes macrophages and neutrophils in LUAD patient cohorts. These might be the reason that higher mRNA and protein levels of TMPRSS2 are associated with better prognosis in LUAD cohorts rather than in LUSC cohorts. Furthermore, we found that TMPRSS2 was positively correlated with the prognosis in patient nonresponse to anti-PD-1 therapy. Therefore, we made an inference that increasing the expression level of TMPRSS2 may improve the anti-PD-1 immunotherapy efficacy. Finally, five ginsenosides candidates with high inhibition potency were screened from the natural chemical library to be used as TMPRSS2 inhibitors. Conclusion: All these may imply that TMPRSS2 might be a novel prognostic biomarker and serve as a potential immunomodulator target of immunotherapy combination therapies in LUAD patients nonresponse to anti-PD-1 therapy. Also, these findings may suggest we should pay more attention to LUAD patients, especially those infected with COVID-19, who should avoid medicating TMPRSS2 inhibitors, such as ginsenosides to gain prophylactic and therapeutic benefits against COVID-19.

4.
J Clin Med ; 12(3)2023 Feb 01.
Article in English | MEDLINE | ID: covidwho-2225408

ABSTRACT

Beneficial off-target effects of the Bacillus Calmette-Guérin (BCG) vaccination might offer general protection from respiratory tract infections. We conducted a systematic review and meta-analysis of published randomized controlled trials (RCTs) to ascertain BCG vaccination effectiveness against COVID-19. We looked up English RCTs from 1 January 2019 to 15 November 2022 in Embase, the Cochrane Library, and the Web of Science in this systematic review and meta-analysis. Nine RCTs, including 7963 participants, were included. The infection rate of COVID-19 was not decreased in people who were vaccinated with BCG (OR, 0.96; 95% CI, 0.82-1.13; I2 = 4%), and the BCG vaccination group did not have decreased COVID-19 related-hospitalization (OR, 0.66; 95% CI, 0.37-1.18; I2 = 42%), admission to the ICU (OR, 0.25; 95% CI, 0.05-1.18; I2 = 0%), and mortality (OR, 0.64; 95% CI, 0.17-2.44; I2 = 0%) compared with the control group. There is not sufficient evidence to support the use of BCG vaccination in the prevention of COVID-19 infection and severe COVID-19 and avoid overstating the role of BCG vaccination leading to its misuse.

6.
Arch Bronconeumol ; 58: 32-38, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1783181

ABSTRACT

As with the rapid increase of the number of patients who have recovered from COVID-19 globally, there needs to be a major shift of the focus from rapid pathogen detection, treatment and prevention to the promotion of better recovery. Notwithstanding the scarcity of our understandings, recent studies have unraveled a plethora of pulmonary and systemic consequences which require medical attention. These consequences remained as of the end of follow-up which ranged from 1 month to 1 year. Here, we review the consequences of COVID-19 in terms of the residual symptoms, radiological and functional manifestations, and identify the potential risk factors that contribute to a prolonged recovery. We also summarize the benefits of clinical interventions (particularly the pulmonary rehabilitation program), and address several undetermined concerns and key future research directions.


Como consecuencia del rápido aumento del número de pacientes que se han recuperado de la COVID-19 en todo el mundo, es necesario cambiar el enfoque de la detección rápida del patógeno, el tratamiento y la prevención para promover una mejor recuperación. A pesar de la escasez de nuestros conocimientos, estudios recientes han desvelado una plétora de consecuencias pulmonares y sistémicas que requieren atención médica. Estas consecuencias se mantienen al final del seguimiento, que oscila entre 1 mes y 1 año. Aquí se hace una revisión de las consecuencias de la COVID-19 en términos de síntomas residuales y manifestaciones radiológicas y funcionales y se identifican los posibles factores de riesgo que contribuyen a una recuperación demorada. También se resumen los beneficios de las intervenciones clínicas (en particular el programa de rehabilitación pulmonar) y se abordan varias preocupaciones no resueltas y direcciones clave de investigación futura.


Subject(s)
COVID-19 , Forecasting , Humans , Lung/diagnostic imaging , Risk Factors
7.
EMBO Mol Med ; 14(5): e14844, 2022 05 09.
Article in English | MEDLINE | ID: covidwho-1776709

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID-19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID-19. Plasma VEGF level was particularly elevated in patients with GI symptoms and significantly correlated with intestinal edema and disease progression. Through an animal model mimicking intestinal inflammation upon stimulation with SARS-CoV-2 spike protein, we further revealed that VEGF was over-produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS-CoV-2 spike promoted VEGF production through activating the Ras-Raf-MEK-ERK signaling in enterocytes, but not in endothelium, and inducing permeability and inflammation. Blockage of the ERK/VEGF axis was able to rescue vascular permeability and alleviate intestinal inflammation in vivo. These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Enterocytes/metabolism , Humans , Inflammation/metabolism , Spike Glycoprotein, Coronavirus , Vascular Endothelial Growth Factor A
8.
Chin Med J (Engl) ; 134(16): 1967-1976, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1769434

ABSTRACT

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).


Subject(s)
COVID-19 , Aged , Antibodies, Viral , COVID-19/therapy , COVID-19 Vaccines , Double-Blind Method , Humans , Immunization, Passive , Recombinant Fusion Proteins , SARS-CoV-2 , COVID-19 Serotherapy
9.
Front Psychiatry ; 12: 771621, 2021.
Article in English | MEDLINE | ID: covidwho-1581155

ABSTRACT

Background: The 2019 coronavirus (COVID-19) had caused a global pandemic and disrupted millions of lives. Cancer patients are a special group at greater risk of contracting viruses. This study aimed to evaluate the anxiety and depression status of cancer patients undergoing radiotherapy during the COVID-19 epidemic. Methods: 396 cancer patients who underwent radiotherapy were enrolled in this study. The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate patient anxiety and depression, respectively. 373 cancer patients completed the questionnaires. Results: During the COVID-19 outbreak, the incidence of anxiety and depression in cancer patients were 34.9 and 33.8%, respectively. Approximately 31.4% of tumor radiotherapy patients had anxiety and depression. Based on univariate analysis, age, work status, education level, and clinical stage were related to anxiety and depression in cancer patients. Based on multiple regression analysis, age and clinical stage were related to anxiety, but only age was related to depression. Conclusions: Due to the COVID-19 pandemic, cancer patients experienced increased psychological problems. Our results have contributed to a better understanding of these psychological problems in cancer patients and provide a basis for psychological counseling and intervention.

10.
Front Cardiovasc Med ; 8: 738044, 2021.
Article in English | MEDLINE | ID: covidwho-1497031

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown. Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded. Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R 2 = -0.636, p < 0.001). Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.

11.
Int J Mol Sci ; 22(19)2021 Sep 26.
Article in English | MEDLINE | ID: covidwho-1463703

ABSTRACT

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system-related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate the antiviral effect on the exosomes of teleost fish. Exosomes isolated from mandarin fish serum by ultra-centrifugation were internalized by mandarin fish fry cells and were able to inhibit Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigate the underlying mechanisms of exosomes in inhibiting ISKNV infection, the protein composition of serum-derived exosomes was analyzed by mass spectrometry. It was found that myxovirus resistance 1 (Mx1) was incorporated by exosomes. Furthermore, the mandarin fish Mx1 protein was proven to be transferred into the recipient cells though exosomes. Our results showed that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication, which suggested an underlying mechanism of the exosome antivirus in that it incorporates Mx1 protein and delivery into recipient cells. This study provided evidence for the important antiviral role of exosomes in the immune system of teleost fish.


Subject(s)
DNA Virus Infections , Exosomes , Fish Diseases , Fish Proteins , Fishes , Iridoviridae , Myxovirus Resistance Proteins , Animals , Cell Line , DNA Virus Infections/blood , DNA Virus Infections/immunology , DNA Virus Infections/veterinary , Exosomes/immunology , Exosomes/metabolism , Fish Diseases/blood , Fish Diseases/immunology , Fish Proteins/blood , Fish Proteins/immunology , Fishes/blood , Fishes/immunology , Fishes/virology , Iridoviridae/immunology , Iridoviridae/metabolism , Myxovirus Resistance Proteins/blood , Myxovirus Resistance Proteins/immunology
12.
N Engl J Med ; 382(18): 1708-1720, 2020 04 30.
Article in English | MEDLINE | ID: covidwho-1428982

ABSTRACT

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).


Subject(s)
Betacoronavirus , Coronavirus Infections , Disease Outbreaks , Pandemics , Pneumonia, Viral , Adolescent , Adult , Aged , COVID-19 , Child , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Female , Fever/etiology , Humans , Male , Middle Aged , Patient Acuity , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2 , Young Adult
13.
Aging Dis ; 12(3): 705-709, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1315006

ABSTRACT

COVID-19 is now causing a global pandemic, there is a demand to explain the different clinical patterns between children and adults. To clarify the organs/cell types vulnerable to COVID-19 infection and the potential age-depended expression patterns of five factors (ACE2, TMPRSS2, MTHFD1, CTSL, CTSB) associated with clinical symptoms. In this study, we analyzed expression levels of five COVID-19 host dependency factors in multiple adult and fetal human organs. The results allowed us to grade organs at risk and also pointed towards the target cell types in each organ mentioned above. Based on these results we constructed an organ- and cell type-specific vulnerability map of the expression levels of the five COVID-19 factors in the human body, providing insight into the mechanisms behind the symptoms, including the non-respiratory symptoms of COVID-19 infection and injury. Also, the different expression patterns of the COVID-19 factors well demonstrate an explanation that the different clinical patterns between adult and children/infants.

14.
Immun Inflamm Dis ; 9(4): 1358-1369, 2021 12.
Article in English | MEDLINE | ID: covidwho-1303261

ABSTRACT

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has emerged as an international pandemic. COVID-19 patients with myocardial injury might need special attention. However, an understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury to COVID-19 patients. METHODS: This retrospective, single-center study finally included 304 hospitalized COVID-19 cases confirmed by real-time reverse-transcriptase polymerase chain reaction from January 11 to March 25, 2020. Myocardial injury was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19-associated mortality. RESULTS: Of 304 COVID-19 patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury, 27 patients without myocardial injury on admission). COVID-19 patients with myocardial injury had more comorbidities (hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease); lower lymphocyte counts, higher C-reactive protein (CRP; median, 84.9 vs. 28.5 mg/L; p < .001), procalcitonin levels (median, 0.29 vs. 0.06 ng/ml; p < .001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio [HR] = 7.02; 95% confidence interval [CI], 4.45-11.08; p < .001) than those without myocardial injury. Myocardial injury (HR = 4.55; 95% CI, 2.49-8.31; p < .001), senior age, CRP levels, and novel coronavirus pneumonia types on admission were independent predictors to mortality in COVID-19 patients. CONCLUSIONS: COVID-19 patients with myocardial injury on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury and higher Hs-TnI are both strongest independent predictors to COVID-19-related mortality after adjusting confounding factors.


Subject(s)
COVID-19 , Aged , Female , Humans , Male , Pandemics , Prognosis , Retrospective Studies , SARS-CoV-2
15.
Ann Transl Med ; 9(11): 941, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1278842

ABSTRACT

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

17.
Case Rep Womens Health ; 31: e00321, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1213126

ABSTRACT

The effects of SARS-CoV-2 infection in the first trimester on the pregnant woman and the fetus remain unclear. We describe the complete follow-up of a pregnant woman with asymptomatic SARS-CoV-2 infection in the first trimester. The woman tested positive for SARS-CoV-2 viral RNA in nasopharyngeal swabs in her seventh week of gestation and was admitted to a local hospital for treatment. Although the woman had a BMI above 28 and a total gestational weight gain of 21 kg, no pregnancy complications or severe complications related to SARS-CoV-2 were reported. An ultrasound scan identified no fetal abnormalities at 22 weeks. The pregnancy ended at term (37 weeks), and the newborn's birth weight was 3100 g. Placental insufficiency was revealed by placental histology examination but this appeared not to be related to the SARS-CoV-2 infection. In-situ hybridisation and immunohistochemical tests for SARS-CoV-2 RNA, spike protein 1, and nucleocapsid proteins were negative. However, ACE-2 was positive in samples of the placenta, umbilical cord and fetal membrane. The baby was followed up through to 10 days after birth and grew normally. Our results suggest that asymptomatic SARS-CoV-2 infection in the first trimester of pregnancy might not have significant harmful effects on the mother and the developing fetus. This finding may be of interest to the general public, midwives and general practitioners. However, large population studies are needed to confirm our findings.

19.
Ann Palliat Med ; 10(3): 3307-3312, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1168323

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was broken out in December 2019 and soon became a global health emergency. Effective treatment for COVID-19 is urgently needed. In the present study, we aimed to evaluate the antiviral effect of Arbidol vs. Chloroquine in treating COVID-19. METHODS: We retrospectively analyzed 62 patients with COVID-19 diagnosed according to the guidelines for diagnosis and treatment of COVID-19 in China. They were divided into two groups depending on the antiviral drugs that they received. Participants in the Arbidol group (n=42) received 0.2 g Arbidol, tid for 10 days,and those in Chloroquine group (n=20) received 500 mg Chloroquine, bid for 10 days. The coronavirus negative conversion time and the length of hospital stay were analyzed and compared between the two groups. RESULTS: There was no significant difference in demographic and clinical characteristics between the two groups. After antiviral treatment, the nasopharyngeal specimen negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the length of hospital stay in the Arbidol group were significantly shorter than those in the Chloroquine group (18.50 vs. 25.05 days, P=0.001; 23.52 vs. 28.75 days, P=0.001). Adverse events observed during the antiviral treatment period were comparable between the two groups. Overall, 3 (7.14%) participants in the Arbidol group and 4 (20.0%) in the Chloroquine group experienced adverse events during antiviral treatment. CONCLUSIONS: These results suggest that Arbidol is advantageous over Chloroquine in terms of the SARS-CoV-2 negative conversion and the length of hospital stay in treating COVID-19 patients.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Chloroquine/therapeutic use , Indoles/therapeutic use , China , Chloroquine/adverse effects , Humans , Length of Stay , Retrospective Studies
20.
BMC Public Health ; 21(1): 551, 2021 03 20.
Article in English | MEDLINE | ID: covidwho-1143199

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) confirmed cases overseas have continued to rise in the last months, and many people overseas have chosen to return to China. This increases the risk of a large number of imported cases which may cause a relapse of the COVID-19 outbreak. In order to prevent imported infection, the Shenzhen government has implemented a closed-loop management strategy using nucleic acid testing (NAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and requiring 14 days of medical observation for individuals with an overseas tour history (Hong Kong, Macao, Taiwan province and other countries). Our study aims to describe the status of COVID-19 infection among people entering Shenzhen, and to evaluate the effect of the closed-loop management strategy. METHODS: We undertook a descriptive study and risk analysis by the entry time, time of reporting, and local confirmed cases in countries of origin. The NAT were completed in Shenzhen Center for Disease Control and Prevention (CDC), ten district-level CDCs, and fever clinics. RESULTS: A total of 86,844 people from overseas entered Shenzhen from January 1 to April 18, 2020; there were 39 imported COVID cases and 293 close contacts. The infection rate of people entering was 4.49‰ [95% Confidence interval (CI): 3.26‰-6.05‰]. Fourteen imported cases (35.9%) came from the UK, and nine (23.08%) came from the USA. People entering from the USA since March 9 or from the UK since March 13 are the high-risk population. As of July 17, there have been no new confirmed cases in Shenzhen for 153 days, and the numbers of confirmed case, close contacts, and asymptomatic cases are 0. CONCLUSIONS: The closed-loop management has been effective in preventing imported infection and controlling domestic relapse. The distribution of entry time and report time for imported cases overseas was similar. This shows that it is important to implement closed-loop management at the port of entry.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control/methods , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/prevention & control , China/epidemiology , Humans , SARS-CoV-2
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