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1.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314714

ABSTRACT

Very recently the new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and the coronavirus disease 2019 (COVID-19) declared a pandemic by the World Health Organization. The pandemic has a number of consequences for the ongoing clinical trials in non-COVID-19 conditions. Motivated by four currently ongoing clinical trials in a variety of disease areas we illustrate the challenges faced by the pandemic and sketch out possible solutions including adaptive designs. Guidance is provided on (i) where blinded adaptations can help;(ii) how to achieve type I error rate control, if required;(iii) how to deal with potential treatment effect heterogeneity;(iv) how to utilize early readouts;and (v) how to utilize Bayesian techniques. In more detail approaches to resizing a trial affected by the pandemic are developed including considerations to stop a trial early, the use of group-sequential designs or sample size adjustment. All methods considered are implemented in a freely available R shiny app. Furthermore, regulatory and operational issues including the role of data monitoring committees are discussed.

3.
World J Clin Cases ; 9(3): 528-539, 2021 Jan 26.
Article in English | MEDLINE | ID: covidwho-1069992

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has posed a serious threat to global public health security. With the increase in the number of confirmed cases globally, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Despite atypical pneumonia as the primary symptom, liver dysfunction has also been observed in many clinical cases and is associated with the mortality risk in patients with COVID-19, like severe acute respiratory syndrome and Middle East respiratory syndrome. Here we will provide a schematic overview of the clinical characteristics and the possible mechanisms of liver injury caused by severe acute respiratory syndrome coronavirus 2 infection, which may provide help for optimizing the management of liver injury and reducing mortality in COVID-19 patients.

4.
Hepatol Int ; 14(5): 723-732, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-834069

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. METHODS: A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. RESULTS: Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. CONCLUSION: Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.


Subject(s)
Coronavirus Infections , Cytokines/blood , Hepatic Insufficiency , Leukocyte Count/methods , Liver Function Tests , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Female , Hepatic Insufficiency/blood , Hepatic Insufficiency/epidemiology , Hepatic Insufficiency/virology , Humans , Incidence , Liver Function Tests/methods , Liver Function Tests/statistics & numerical data , Male , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Retrospective Studies , Risk Factors , SARS-CoV-2 , Sex Factors
5.
Stat Biopharm Res ; 12(4): 461-477, 2020 Aug 19.
Article in English | MEDLINE | ID: covidwho-670822

ABSTRACT

Very recently the new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and the coronavirus disease 2019 (COVID-19) declared a pandemic by the World Health Organization. The pandemic has a number of consequences for ongoing clinical trials in non-COVID-19 conditions. Motivated by four current clinical trials in a variety of disease areas we illustrate the challenges faced by the pandemic and sketch out possible solutions including adaptive designs. Guidance is provided on (i) where blinded adaptations can help; (ii) how to achieve Type I error rate control, if required; (iii) how to deal with potential treatment effect heterogeneity; (iv) how to use early read-outs; and (v) how to use Bayesian techniques. In more detail approaches to resizing a trial affected by the pandemic are developed including considerations to stop a trial early, the use of group-sequential designs or sample size adjustment. All methods considered are implemented in a freely available R shiny app. Furthermore, regulatory and operational issues including the role of data monitoring committees are discussed.

7.
Stat Biopharm Res ; 12(4): 419-426, 2020 Aug 17.
Article in English | MEDLINE | ID: covidwho-629452

ABSTRACT

Abstract-The COVID-19 pandemic has a global impact on the conduct of clinical trials of medical products. This article discusses implications of the COVID-19 pandemic on clinical research methodology aspects and provides points to consider to assess and mitigate the risk of seriously compromising the integrity and interpretability of clinical trials. The information in this article will support discussions that need to occur cross-functionally on an ongoing basis to "integrate all available knowledge from the ethical, the medical, and the methodological perspective into decision making." This article aims at facilitating: (i) risk assessments of the impact of the pandemic on trial integrity and interpretability; (ii) identification of the relevant data and information related to the impact of the pandemic on the trial that needs to be collected; (iii) short-term decision making impacting ongoing trial operations; (iv) ongoing monitoring of the trial conduct until completion, including the possible involvement of data monitoring committees, and adequately documenting all measures taken to secure trial integrity throughout and after the pandemic, and (v) proper analysis and interpretation of the eventual interim or final trial data.

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