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1.
Emerg Microbes Infect ; 11(1): 1115-1125, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1799501

ABSTRACT

Diabetes mellitus (DM) is one of the most common underlying diseases that may aggravates COVID-19. In the present study, we explored islet function, the presence of SARS-CoV-2 and pathological changes in the pancreas of patients with COVID-19. Oral glucose tolerance tests (OGTTs) and the C-peptide release test demonstrated a decrease in glucose-stimulated C-peptide secretory capacity and an increase in HbA1c levels in patients with COVID-19. The prediabetic conditions appeared to be more significant in the severe group than in the moderate group. SARS-CoV-2 receptors (ACE2, CD147, TMPRSS2 and neuropilin-1) were expressed in pancreatic tissue. In addition to SARS-CoV-2 virus spike protein and virus RNA, coronavirus-like particles were present in the autophagolysosomes of pancreatic acinar cells of a patient with COVID-19. Furthermore, the expression and distribution of various proteins in pancreatic islets of patients with COVID-19 were altered. These data suggest that SARS-CoV-2 in the pancreas may directly or indirectly impair islet function.


Subject(s)
COVID-19 , Diabetes Mellitus , C-Peptide/metabolism , Diabetes Mellitus/metabolism , Humans , Pancreas , SARS-CoV-2
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323677

ABSTRACT

Background: More and more studies showed pneumothorax is a complication of the 2019 novel coronavirus disease (COVID-19). But no autopsy findings of pneumothorax in COVID-19 decedent were reported, and direct relations between pneumothorax and lung pathology in these decedents were not discussed so far. Methods: A 62-year-old man with COVID-19 presenting with persistent hypoxemia and suddenly dead, who was treated by mechanical ventilation in the intensive care unit (ICU) for 5 days. A systemic autopsy examination of COVID-19 decedent, including histopathology study, was conducted and the medical record, chest computerized tomography (CT) image were reviewed by forensic pathologists and clinicians. Results: Severe pneumothorax, diffuse alveolar damage and airway obstruction were observed. Pneumothorax should be one of the causes of death. Conclusion: Pneumothorax, due to SARS-CoV-2 infection, is a fatal complication of COVID-19. Regular examination of chest CT or X-ray and airway management are important to clinical treatment.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316032

ABSTRACT

Despite widespread interest in the pathophysiology of COVID-19 in respiratory and cardiovascular systems, little is known about the morphologic and molecular changes in the testis of patients with COVID-19 and the effects of SARS-CoV-2 infection on male fertility. We report here on the pathophysiology and molecular feature of testes obtained at autopsy from six men with COVID-19, as compared with those of testes from three men with age-matched, uninfected SARS-CoV-2. Our histopathological results showed that all COVID-19 patients had severe spermatogenesis damages compared with controls. Importantly, we detected the nuclear acid of the SARS-CoV-2 virus, viral particles, and SARS-CoV-2 spike S1 protein in COVID-19 patient testes, and we also found ACE2 and TMPRSS2 significantly elevated in the testes from COVID-19 patients. Furthermore, we observed a prominent leukocyte infiltration, including CD3+ T lymphocytes, CD20+ B lymphocytes, CD68+ macrophages, HLA-DR+ myeloid cells, and CD38+ plasma cells in the testes of COVID-19 patients. RNA-Seq analyses further revealed SARS-CoV-2 infection could lead to dysfunction of the genes that regulate the spermatogenesis and inflammation response-related pathways. Collectively, our pathological and molecular examination findings indicate that SARS-CoV-2 could directly attack testicular cells, thereby inducing the damage of testicular immune privilege and spermatogenesis defects.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313395

ABSTRACT

Background: The progression of coagulation in COVID-19 patients with confirmed discharge status and the combination of autopsy with complete hemostasis parameters have not been well studied. Objective: To clarify the thrombotic phenomena and hemostasis state in COVID-19 patients based on epidemiological statistics combining autopsy and statistical analysis. Methods: : Using autopsy results from 9 patients with COVID-19 pneumonia and the medical records of 407 patients, including 39 deceased patients whose discharge status was certain, time-sequential changes in 11 relevant indices within mild, severe and critical infection throughout hospitalization according to the Chinese National Health Commission (NHC) guidelines were evaluated. Statistical tools were applied to calculate the importance of 11 indices and the correlation between those indices and the severity of COVID-19. Results: : At the beginning of hospitalization, platelet (PLT) counts were significantly reduced in critically ill patients compared with severely or mildly ill patients. Blood glucose (GLU), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer levels in critical patients were increased compared with mild and severe patients during the entire admission period. The International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was also high in critical patients. In the relatively late stage of nonsurvivors, the temporal changes in PLT count, PT, and D-dimer levels were significantly different from those in survivors. A random forest model indicated that the most important feature was PT followed by D-dimer, indicating their positive associations with disease severity. Autopsy of deceased patients fulfilling diagnostic criteria for DIC revealed microthromboses in multiple organs. Conclusions: Combining autopsy data, time-sequential changes and statistical methods to explore hemostasis-relevant indices among the different severities of the disease helps guide therapy and detect prognosis in COVID-19 infection.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296091

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293601

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

7.
Cell Res ; 31(12): 1230-1243, 2021 12.
Article in English | MEDLINE | ID: covidwho-1475291

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.


Subject(s)
COVID-19/pathology , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Cytokines/genetics , Cytokines/metabolism , Down-Regulation/drug effects , ErbB Receptors/metabolism , Humans , Imidazoles/pharmacology , Imidazoles/therapeutic use , Indoles/pharmacology , Indoles/therapeutic use , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Mutation , Receptor-Interacting Protein Serine-Threonine Kinases/antagonists & inhibitors , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Survival Rate , Transcriptome/drug effects , Viral Load/drug effects , Virus Internalization
8.
Pathol Res Pract ; 227: 153610, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401790

ABSTRACT

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.


Subject(s)
Apoptosis , Autophagy , COVID-19/pathology , SARS-CoV-2/pathogenicity , Spleen/pathology , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Autopsy , Biomarkers/analysis , CD11b Antigen/analysis , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Caspase 3/analysis , Host-Pathogen Interactions , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Phosphorylation , Proto-Oncogene Proteins c-akt/analysis , Proto-Oncogene Proteins c-bcl-2/analysis , SARS-CoV-2/immunology , Sequestosome-1 Protein/analysis , Spike Glycoprotein, Coronavirus/analysis , Spleen/immunology , Spleen/virology
9.
Front Med (Lausanne) ; 8: 630765, 2021.
Article in English | MEDLINE | ID: covidwho-1295652

ABSTRACT

Background: The morbidity and mortality of coronavirus disease 2019 (COVID-19) are still increasing. This study aimed to assess the quality of relevant COVID-19 clinical practice guidelines (CPGs) and to compare the similarities and differences between recommendations. Methods: A comprehensive search was conducted using electronic databases (PubMed, Embase, and Web of Science) and representative guidelines repositories from December 1, 2019, to August 11, 2020 (updated to April 5, 2021), to obtain eligible CPGs. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the quality of CPGs. Four authors extracted relevant information and completed data extraction forms. All data were analyzed using R version 3.6.0 software. Results: In total, 39 CPGs were identified and the quality was not encouragingly high. The median score (interquartile range, IQR) of every domain from AGREE II for evidence-based CPGs (EB-CPGs) versus (vs.) consensus-based CPG (CB-CPGs) was 81.94% (75.00-84.72) vs. 58.33% (52.78-68.06) in scope and purpose, 59.72% (38.89-75.00) vs. 36.11% (33.33-36.11) in stakeholder involvement, 64.58% (32.29-71.88) vs. 22.92% (16.67-26.56) in rigor of development, 75.00% (52.78-86.81) vs. 52.78% (50.00-63.89) in clarity of presentation, 40.63% (22.40-62.50) vs. 20.83% (13.54-25.00) in applicability, and 58.33% (50.00-100.00) vs. 50.00% (50.00-77.08) in editorial independence, respectively. The methodological quality of EB-CPGs were significantly superior to the CB-CPGs in the majority of domains (P < 0.05). There was no agreement on diagnosis criteria of COVID-19. But a few guidelines show Remdesivir may be beneficial for the patients, hydroxychloroquine +/- azithromycin may not, and there were more consistent suggestions regarding discharge management. For instance, after discharge, isolation management and health status monitoring may be continued. Conclusions: In general, the methodological quality of EB-CPGs is greater than CB-CPGs. However, it is still required to be further improved. Besides, the consistency of COVID-19 recommendations on topics such as diagnosis criteria is different. Of them, hydroxychloroquine +/- azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; isolation management and health status monitoring after discharge may be still necessary. Chemoprophylaxis, including SARS-CoV 2 vaccines and antiviral drugs of COVID-19, still require more trials to confirm this.

10.
Cell Death Differ ; 28(9): 2765-2777, 2021 09.
Article in English | MEDLINE | ID: covidwho-1195611

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.


Subject(s)
COVID-19/virology , Giant Cells/virology , Lymphocytes/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/pathology , Cell Line , Cell Line, Tumor , Giant Cells/pathology , HEK293 Cells , HeLa Cells , Humans , Jurkat Cells , K562 Cells , Lymphocytes/pathology , Virus Internalization , Virus Replication/genetics
11.
EClinicalMedicine ; 34: 100839, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1188500

ABSTRACT

BACKGROUND: With the increased number of patients discharged after having COVID-19, more and more studies have reported cases whose retesting was positive (RP) during the convalescent period, which brings a new public health challenge to the world. METHODS: We searched PubMed, Web of Science, The Cochrane Library, CNKI, WanFang and VIP from December 1, 2019 to December 31, 2020. The included studies were assessed using JBI critical appraisal tools and Newcastle-Ottawa Scale. The RP rate of discharge patients was analyzed by a meta-analysis. We adhered to PRISMA reporting guideline. FINDINGS: We have included 117 studies with 2669 RP participants after discharge. The methodological quality of 66 case reports were low to high, 42 case series and 3 cohort study were moderate to high, 3 case-control studies were moderate and 3 cross-sectional studies were low to moderate. The clinical manifestations of most RP patients were mild or asymptomatic, and CT imaging and laboratory examinations were usually normal. The existing risk factors suggest that more attention should be paid to sever patients, elderly patients, and patients with co-morbidities. The summary RP rate was 12·2% (95% CI 10·6-13·7) with high heterogeneity (I2  = 85%). INTERPRETATION: To date, the causes and risk factors of RP result in discharged patients are not fully understood. High-quality etiological and clinical studies are needed to investigate these issues to further help us to make strategies to control and prevent its occurrence.

12.
Front Public Health ; 9: 638975, 2021.
Article in English | MEDLINE | ID: covidwho-1156166

ABSTRACT

Objective: Understanding gender differences in responses of health-care workers (HCWs) to COVID-19 outbreak is an effective way to promote customized supports. Methods: During February 2020, 103 HCWs infected with COVID-19 (64 females and 39 males) and 535 uninfected HCWs (383 females and 152 males) were recruited in a cross-sectional study. Level of attention, six emotional status, and self-evaluation of eight protective measures were recorded. Multivariable Firth's logistic regressions were applied to explored independent effect of gender. Results: During early outbreak, female HCWs were more likely to give greater attention, adjusted OR:1.92 (95%CI 1.14-3.23) in total HCWs. Higher proportion of anxiety was observed in female HCWs, adjusted OR:3.14 (95%CI 1.98-4.99) for total HCWs, 4.32(95%CI 1.32-14.15) for infected HCWs and 2.97 (1.78, 4.95) for uninfected HCWs. Proportion of pessimism, fear, full of fighting spirit, and optimism were low, and no gender differences were observed. During a later outbreak, a majority of HCWs reported being very familiar with eight protective measures. After training, a proportion of high self-evaluation in hand hygiene, wearing gloves, and surgical masks increased independently in female HCWs, and adjusted ORs were 3.07 (95% CI 1.57-5.99), 2.37 (95% CI 1.26-4.49), and 1.92 (95% CI 1.02-3.62), respectively. Infection status amplified gender difference in anxiety, hand hygiene, and glove wearing. Conclusion: Female HCWs perceived the outbreak seriously, effective emotional and psychological well-ness should be targeted at female HCWs preferentially, and male HCWs should be encouraged to express their feelings and be further trained.


Subject(s)
Adaptation, Psychological , COVID-19/psychology , Disease Outbreaks/statistics & numerical data , Health Personnel/psychology , Health Risk Behaviors , Infections/psychology , Stress, Psychological , Adult , COVID-19/epidemiology , China/epidemiology , Cross-Sectional Studies , Female , Health Personnel/statistics & numerical data , Humans , Male , Middle Aged , SARS-CoV-2 , Sex Factors , Surveys and Questionnaires
13.
Natl Sci Rev ; 7(12): 1868-1878, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1087785

ABSTRACT

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents-findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1ß). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.

14.
Thromb J ; 19(1): 8, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1079245

ABSTRACT

BACKGROUND: The progression of coagulation in COVID-19 patients with confirmed discharge status and the combination of autopsy with complete hemostasis parameters have not been well studied. OBJECTIVE: To clarify the thrombotic phenomena and hemostasis state in COVID-19 patients based on epidemiological statistics combining autopsy and statistical analysis. METHODS: Using autopsy results from 9 patients with COVID-19 pneumonia and the medical records of 407 patients, including 39 deceased patients whose discharge status was certain, time-sequential changes in 11 relevant indices within mild, severe and critical infection throughout hospitalization according to the Chinese National Health Commission (NHC) guidelines were evaluated. Statistical tools were applied to calculate the importance of 11 indices and the correlation between those indices and the severity of COVID-19. RESULTS: At the beginning of hospitalization, platelet (PLT) counts were significantly reduced in critically ill patients compared with severely or mildly ill patients. Blood glucose (GLU), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer levels in critical patients were increased compared with mild and severe patients during the entire admission period. The International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was also high in critical patients. In the relatively late stage of nonsurvivors, the temporal changes in PLT count, PT, and D-dimer levels were significantly different from those in survivors. A random forest model indicated that the most important feature was PT followed by D-dimer, indicating their positive associations with disease severity. Autopsy of deceased patients fulfilling diagnostic criteria for DIC revealed microthromboses in multiple organs. CONCLUSIONS: Combining autopsy data, time-sequential changes and statistical methods to explore hemostasis-relevant indices among the different severities of the disease helps guide therapy and detect prognosis in COVID-19 infection.

17.
Front Pharmacol ; 11: 554172, 2020.
Article in English | MEDLINE | ID: covidwho-945685

ABSTRACT

COVID-19 has been announced pandemic by WHO and over 17,000,000 people infected (Till April 21st 2020). The disease is currently under control in China, with a curative rate of 86.8%. Chloroquine (CQ) is an old anti-malarial drug with good tolerability, which had proved to be effective in previous SARS-coronavirus, which spread and disappeared between 2002-2003. In vitro studies demonstrated the efficacy of CQ in curing COVID-19. Consequently, via analytical PBPK modeling, a further preliminary clinical trial has proved the efficacy and safety of CQ in China., and multiple clinical trials were registered and approved to investigate the activity of other analogs of CQ against COVID-19. We have listed all the clinical trials and made a meta-analysis of published data of hydroxychloroquine (HCQ). HCQ could increase the CT improvement and adverse reactions (ADRs) significantly though there was considerable heterogeneity among current researches. Actually, CQ and its analogs have unique pharmacokinetic characteristics, which would induce severe side effects in some circumstances. We have then summarized pharmacological considerations for these drugs so as to provide to the busy clinicians to avoid potential side effects when administered CQ or its analogs to COVID-19 patients, especially in the elderly, pediatrics, and pregnancies.

18.
Front Pharmacol ; 11: 540187, 2020.
Article in English | MEDLINE | ID: covidwho-782038

ABSTRACT

OBJECTIVE: The quality and rationality of many recently registered clinical studies related to coronavirus disease 2019 (COVID-19) needs to be assessed. Hence, this study aims to evaluate the current status of COVID-19 related registered clinical trial. METHODS: We did an electronic search of COVID-19 related clinical studies registered between December 1, 2019 and February 21, 2020 (updated to May 28, 2020) from the ClinicalTrials.gov, and collected registration information, study details, recruitment status, characteristics of the subjects, and relevant information about the trial implementation process. RESULTS: A total of 1,706 studies were included 10.0% of which (n=171) were from France, 943 (55.3%) used an interventional design, and 600 (35.2%) used an observational design. Most of studies (73.6%) aimed to recruit fewer than 500 people. Interferon was the main prevention program, and antiviral drugs were the main treatment program. Hydroxychloroquine and chloroquine (230/943, 24.4%) were widely studied. Some registered clinical trials are incomplete in content, and 37.4% of the 1,706 studies may have had insufficient sample size. CONCLUSION: The quality of COVID-19 related studies needs to be improved by strengthening the registration process and improving the quality of clinical study protocols so that these clinical studies can provide high-quality clinical evidence related to COVID-19.

19.
Mil Med Res ; 7(1): 41, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-745023

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.


Subject(s)
Chemoprevention/methods , Clinical Laboratory Techniques/methods , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Betacoronavirus , COVID-19 , COVID-19 Testing , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Evidence-Based Medicine , Female , Humans , Male , Middle Aged , Pandemics/prevention & control , Patient Discharge/standards , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Practice Guidelines as Topic , SARS-CoV-2
20.
Chin. J. Evid.-Based Med. ; 6(20): 723-736, 20200601.
Article in Chinese | WHO COVID, ELSEVIER | ID: covidwho-739130

ABSTRACT

Objective To develop the questionnaire and test its reliability for investigating route, prevention, and control of SARS-CoV-2 infection in medical staffs. Methods This questionnaire was development based on the COVID-19 relevant guidelines, official documents issued by the National Health Committee of the People's Republic of China, and published studies. The development group performed repeated discussions and drafted the first questionnaire, then performed expert consultation and revised the draft according to their suggestions. Eventually, some frontline medical staffs were invited to carry out pre-test investigation of the questionnaire and test its reliability. Results The first draft included 48 items; 18 experts were invited in the first round questionnaire and 10 experts in the second round questionnaire. The positive coefficient of experts in these two rounds was both greater than 75%, and the authority coefficient of experts' opinions was greater than 0.70. The variation coefficient of these items was between 0.00 and 0.35, the coordination coefficient of experts was 0.193 (P<0.05). The experts of above two rounds put forward 14 suggestions for text modification or adjustment options of some items; after the development group held repeatedly discussions, a total of 8 items were performed secondary consultation and finally reached consensus. The final questionnaire included two domains of questionnaire before and after confirmed diagnosis. The domain "before confirmed diagnosis" covered 4 sections and 29 items involving infectious cause, plan and knowledge of prevention and control, and psychological symptoms. The domain "after confirmed diagnosis" covered 5 sections and 21 items, included symptoms, treatment, and psychological status after diagnosis; impact on the surrounding environment and people, and awareness of protection after infection. The pre-test results showed that the total items were considerably numerous, some items were difficult to understand, some laboratory results and treatment conditions were ambiguous, etc. After modification and re-testing, the test-re-test reliability of each domain was between 0.74 and 0.93, and the overall re-test reliability of the questionnaire content was 0.82. Conclusions This research has developed a questionnaire for investigating infection process, prevention and control of SARS-CoV-2 infection in medical staff, and the items considered two domains prior to and after confirmed diagnosis. The reliability and practicability of the questionnaire are acceptable.

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