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2.
Biomed Pharmacother ; 129: 110500, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-622561

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19)2 has emerged as a global pandemic. However, as effective treatments for this disease are still unclear, safe and efficient therapies are urgently needed. Qingfei Paidu decoction (QPD)3 is strongly recommended in the Chinese Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 6th Edition). However, clinical research data on the effects of QPD on COVID-19 are scarce. Our study aimed to explore the effects of combined treatment with QPD and Western medicine on COVID-19. METHODS: In this study, 63 patients with confirmed COVID-19 were analyzed. During the first 14 days of hospitalization, patients with deteriorating symptoms were administered QPD along with Western medicine therapy (the antiviral medicine selected from interferon, lopinavir, or arbidol). The clinical characteristics and blood laboratory indices (blood routine, inflammatory factors, and multi-organ biochemical indices) were examined, and the total lung severity scores were evaluated in each patient by reviewing chest computed tomography before treatment and at the end of treatment. RESULTS: Before QPD treatment, the combined treatment group showed higher blood C-reactive protein levels and more severe pulmonary inflammation and clinical symptoms than the Western medicine treatment group. Both groups met the discharge criteria after a similar length of hospitalization. At the end of treatment, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in both groups (P <  0.05). In contrast, C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels were improved only in the combined treatment group (P <  0.05), and C-reactive protein and creatine kinase were the most pronounced (P <  0.01). Compared with baseline, at the end of treatment, the proportion of patients with normal values of C-reactive protein, total lymphocyte count, and lactate dehydrogenase were increased in the combined treatment group (P < 0.05), whereas no significant difference was observed in the Western medicine treatment group (P >  0.05). CONCLUSION: The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended to mitigate the extent of multi-organ impairment. Long-term randomized controlled trials with follow-up evaluations are required to confirm the results presented here.


Subject(s)
Antiviral Agents/administration & dosage , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/administration & dosage , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Therapy, Combination , Female , Hospitalization/statistics & numerical data , Humans , Indoles/administration & dosage , Interferons/administration & dosage , Length of Stay , Lopinavir/administration & dosage , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Young Adult
3.
Clin Sci (Lond) ; 134(12): 1295-1300, 2020 06 26.
Article in English | MEDLINE | ID: covidwho-599624

ABSTRACT

We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease's symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/immunology , Extracellular Traps/physiology , Host-Pathogen Interactions/immunology , Pneumonia, Viral/immunology , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Deoxyribonuclease I/therapeutic use , Humans , Immunity, Innate , Multiple Organ Failure/immunology , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy
4.
Life Sci ; 256: 117905, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-506062

ABSTRACT

In light of the outbreak of the 2019 novel coronavirus disease (COVID-19), the international scientific community has joined forces to develop effective treatment strategies. The Angiotensin-Converting Enzyme (ACE) 2, is an essential receptor for cell fusion and engulfs the SARS coronavirus infections. ACE2 plays an important physiological role, practically in all the organs and systems. Also, ACE2 exerts protective functions in various models of pathologies with acute and chronic inflammation. While ACE2 downregulation by SARS-CoV-2 spike protein leads to an overactivation of Angiotensin (Ang) II/AT1R axis and the deleterious effects of Ang II may explain the multiorgan dysfunction seen in patients. Specifically, the role of Ang II leading to the appearance of Macrophage Activation Syndrome (MAS) and the cytokine storm in COVID-19 is discussed below. In this review, we summarized the latest research progress in the strategies of treatments that mainly focus on reducing the Ang II-induced deleterious effects rather than attenuating the virus replication.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/physiopathology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/physiopathology , Coronavirus Infections/enzymology , Coronavirus Infections/virology , Cytokines/metabolism , Down-Regulation , Humans , Macrophage Activation Syndrome/virology , Multiple Organ Failure/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/enzymology , Pneumonia, Viral/virology
5.
Hum Pathol ; 101: 82-88, 2020 07.
Article in English | MEDLINE | ID: covidwho-478593

ABSTRACT

A 65-year-old man was hospitalized owing to fever (38.6 °C) and dry cough since 4 days. He visited Wuhan 8 days ago. At admission, nasopharyngeal swab samples were taken, and polymerase chain reaction analysis confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positivity. On day 9, after admission, the chest computed tomography scan showed diffuse ground-glass shadows in the patient's bilateral lungs. On day 11, his respiratory symptoms worsened. Subsequently, type I respiratory failure was diagnosed, coinciding with kidney injury, and subsequently, type II respiratory failure occurred, coupled with multiorgan failure including the heart and liver. However, the patient's constitution worsened although SARS-CoV-2 tests were negative since day 13. He died on day 21. Lung biopsy showed areas of diffuse alveolar damage, characterized by extensive acute alveolitis with numerous intra-alveolar neutrophil, lymphocyte, and macrophage infiltrations. Microthrombi were seen in the dilated pulmonary capillaries. Immunohistochemistry staining for SARS-CoV-2 N protein was negative. Taken together, the patient died of multiorgan failure although the SARS-CoV-2 infection was cleared already, implicating that for disease worsening, no active SARS-CoV-2 infection is required.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Lung/virology , Pneumonia, Viral/diagnosis , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Aged , Biopsy , Coronavirus Infections/complications , Coronavirus Infections/virology , Disease Progression , Fatal Outcome , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Predictive Value of Tests , Time Factors , Tomography, X-Ray Computed , Viral Load
6.
Life Sci ; 256: 117900, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-459105

ABSTRACT

AIM: Coronavirus disease 2019 (COVID-19) is a novel highly contagious infection caused by SARS-CoV-2, which has been became a global public health challenge. The pathogenesis of this virus is not yet clearly understood, but there is evidence of a hyper-inflammatory immune response in critically ill patients, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. MATERIAL AND METHODS: A literature review was performed to identify relevant articles on COVID-19 published up to April 30, 2020. The search resulted in 361 total articles. After reviewing the titles and abstracts for inclusion, some irrelevant papers were excluded. Additional relevant articles were identified from a review of citations referenced. KEY FINDINGS: SARS-CoV-2, directly and indirectly, affects the immune system and avoids being eliminated in early stages. On the other hand, the secretion of inflammatory cytokines creates critical conditions that lead to multi-organ failure. SIGNIFICANCE: The immune system which is affected by the virus tries to respond via a cytokine storm and hyperinflammation, which itself leads to further multi-organ damage and even death.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/physiopathology , Immune System/virology , Pneumonia, Viral/physiopathology , Betacoronavirus/isolation & purification , Coronavirus Infections/immunology , Coronavirus Infections/virology , Critical Illness , Cytokines/immunology , Humans , Multiple Organ Failure/immunology , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Respiratory Distress Syndrome, Adult/immunology , Respiratory Distress Syndrome, Adult/virology
7.
Am J Respir Crit Care Med ; 201(11): 1380-1388, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-436947

ABSTRACT

Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Adult , Age Factors , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , China/epidemiology , Comorbidity , Coronavirus Infections/mortality , Critical Illness , Female , Hospital Mortality , Humans , Incidence , Lung/pathology , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Pleural Effusion/virology , Pneumonia, Viral/mortality , Tomography, X-Ray Computed
8.
Naunyn Schmiedebergs Arch Pharmacol ; 393(7): 1157-1160, 2020 07.
Article in English | MEDLINE | ID: covidwho-361504

ABSTRACT

Vitamin D is an immunomodulator hormone with an anti-inflammatory and antimicrobial effect with a high safety profile. A lot of COVID-19 infected patients develop acute respiratory distress syndrome (ARDS), which may lead to multiple organ damage. These symptoms are associated with a cytokine storm syndrome. The aim of this letter is to note the 5 crucial points that vitamin D could have protective and therapeutic effects against COVID-19. For that reason, COVID-19 infection-induced multiple organ damage might be prevented by vitamin D.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Coronavirus Infections/complications , Pneumonia, Viral/complications , Vitamin D/administration & dosage , Anti-Inflammatory Agents/pharmacology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Humans , Multiple Organ Failure/prevention & control , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Respiratory Distress Syndrome, Adult/prevention & control , Respiratory Distress Syndrome, Adult/virology , Vitamin D/pharmacology
9.
Hum Pathol ; 101: 82-88, 2020 07.
Article in English | MEDLINE | ID: covidwho-347774

ABSTRACT

A 65-year-old man was hospitalized owing to fever (38.6 °C) and dry cough since 4 days. He visited Wuhan 8 days ago. At admission, nasopharyngeal swab samples were taken, and polymerase chain reaction analysis confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positivity. On day 9, after admission, the chest computed tomography scan showed diffuse ground-glass shadows in the patient's bilateral lungs. On day 11, his respiratory symptoms worsened. Subsequently, type I respiratory failure was diagnosed, coinciding with kidney injury, and subsequently, type II respiratory failure occurred, coupled with multiorgan failure including the heart and liver. However, the patient's constitution worsened although SARS-CoV-2 tests were negative since day 13. He died on day 21. Lung biopsy showed areas of diffuse alveolar damage, characterized by extensive acute alveolitis with numerous intra-alveolar neutrophil, lymphocyte, and macrophage infiltrations. Microthrombi were seen in the dilated pulmonary capillaries. Immunohistochemistry staining for SARS-CoV-2 N protein was negative. Taken together, the patient died of multiorgan failure although the SARS-CoV-2 infection was cleared already, implicating that for disease worsening, no active SARS-CoV-2 infection is required.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Lung/virology , Pneumonia, Viral/diagnosis , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Aged , Biopsy , Coronavirus Infections/complications , Coronavirus Infections/virology , Disease Progression , Fatal Outcome , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Predictive Value of Tests , Time Factors , Tomography, X-Ray Computed , Viral Load
12.
J Microbiol Immunol Infect ; 53(3): 425-435, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-186735

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged in Chinese people in December 2019 and has currently spread worldwide causing the COVID-19 pandemic with more than 150,000 deaths. In order for a SARS-CoV like virus circulating in wild life for a very long time to infect the index case-patient, a number of conditions must be met, foremost among which is the encounter with humans and the presence in homo sapiens of a cellular receptor allowing the virus to bind. Recently it was shown that the SARS-CoV-2 spike protein, binds to the human angiotensin I converting enzyme 2 (ACE2). This molecule is a peptidase expressed at the surface of lung epithelial cells and other tissues, that regulates the renin-angiotensin-aldosterone system. Humans are not equal with respect to the expression levels of the cellular ACE2. Moreover, ACE2 polymorphisms were recently described in human populations. Here we review the most recent evidence that ACE2 expression and/or polymorphism could influence both the susceptibility of people to SARS-CoV-2 infection and the outcome of the COVID-19 disease. Further exploration of the relationship between the virus, the peptidase function of ACE2 and the levels of angiotensin II in SARS-CoV-2 infected patients should help to better understand the pathophysiology of the disease and the multi-organ failures observed in severe COVID-19 cases, particularly heart failure.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/pathology , Genetic Predisposition to Disease/genetics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Amino Acid Sequence/genetics , Female , Heart Failure/virology , Humans , Male , Multiple Organ Failure/virology , Pandemics , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment
13.
Biomed Pharmacother ; 127: 110195, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-154554

ABSTRACT

Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.


Subject(s)
Betacoronavirus , Cardiovascular System/virology , Central Nervous System/virology , Coronavirus Infections , Digestive System/virology , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Urogenital System/virology , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Disease Management , Humans , Multiple Organ Failure/prevention & control , Multiple Organ Failure/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission
14.
Am J Respir Crit Care Med ; 201(11): 1380-1388, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-47397

ABSTRACT

Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Adult , Age Factors , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , China/epidemiology , Comorbidity , Coronavirus Infections/mortality , Critical Illness , Female , Hospital Mortality , Humans , Incidence , Lung/pathology , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Pleural Effusion/virology , Pneumonia, Viral/mortality , Tomography, X-Ray Computed
16.
Am J Respir Crit Care Med ; 201(11): 1372-1379, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-30783

ABSTRACT

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.


Subject(s)
Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus , China/epidemiology , Comorbidity , Coronary Disease/epidemiology , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Retrospective Studies , Tomography, X-Ray Computed , Young Adult
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