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1.
Am J Chin Med ; 48(7): 1539-1552, 2020.
Article in English | MEDLINE | ID: covidwho-1327716

ABSTRACT

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5-7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.


Subject(s)
COVID-19/drug therapy , Coronavirus Infections/drug therapy , Glycyrrhizic Acid/therapeutic use , Middle East Respiratory Syndrome Coronavirus/drug effects , SARS Virus/drug effects , SARS-CoV-2/drug effects , Severe Acute Respiratory Syndrome/drug therapy , Anti-Inflammatory Agents/therapeutic use , COVID-19/epidemiology , COVID-19/virology , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/physiology , Pandemics , SARS Virus/physiology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/virology , Treatment Outcome
2.
Pharmacol Res ; 158: 104904, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318936

ABSTRACT

The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.


Subject(s)
Betacoronavirus/drug effects , Chloroquine/pharmacology , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Homeostasis/drug effects , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Iron/metabolism , Pneumonia, Viral/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/metabolism , Humans , Pandemics , Pneumonia, Viral/metabolism , SARS-CoV-2
3.
Int J Gynaecol Obstet ; 150(1): 53-57, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1196386

ABSTRACT

OBJECTIVE: To study vaginal delivery outcomes and neonatal prognosis and summarize the management of vaginal delivery during the COVID-19 pandemic. METHODS: A retrospective analysis of medical records and comparison of vaginal delivery outcomes between 10 pregnant women with clinical diagnosis of COVID-19 and 53 pregnant women without COVID-19 admitted to Zhongnan Hospital of Wuhan University between January 20 and March 2, 2020. Results of laboratory tests, imaging tests, and SARS-CoV-2 nucleic acid tests were also analyzed in neonates delivered by pregnant women with clinical diagnosis of COVID-19. RESULTS: There were no significant differences in gestational age, postpartum hemorrhage, and perineal resection rates between the two groups. There were no significant differences in birth weight of neonates and neonatal asphyxia rates between the two groups. Neonates delivered by pregnant women with clinical diagnosis of COVID-19 tested negative for SARS-CoV-2 infection. CONCLUSIONS: Under the premise of full evaluation of vaginal delivery conditions and strict protection measures, pregnant women with ordinary type COVID-19 can try vaginal delivery without exacerbation of COVID-19 and without increasing the risk of SARS-CoV-2 infection in neonates.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Delivery, Obstetric/methods , Pneumonia, Viral/complications , Pregnancy Complications, Infectious/virology , Pregnancy Outcome/epidemiology , Adult , Birth Weight , COVID-19 , China/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Hospitalization , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/virology , Pregnancy , Retrospective Studies , SARS-CoV-2 , Vagina/virology
4.
JMIR Med Educ ; 6(2): e20963, 2020 Nov 18.
Article in English | MEDLINE | ID: covidwho-1183730

ABSTRACT

BACKGROUND: In December 2019, COVID-19 emerged and rapidly spread worldwide. Transmission of SARS-CoV-2, the virus that causes COVID-19, is high; as a result, countries worldwide have imposed rigorous public health measures, such as quarantine. This has involved the suspension of medical school classes globally. Medical school attachments are vital to aid the progression of students' confidence and competencies as future physicians. Since the outbreak of COVID-19, medical schools have sought ways to replace medical placements with virtual clinical teaching. OBJECTIVE: The objective of this study was to review the advantages and disadvantages of virtual medical teaching for medical students during the COVID-19 pandemic based on the current emerging literature. METHODS: A brief qualitative review based on the application and effectiveness of virtual teaching during the COVID-19 pandemic was conducted by referencing keywords, including medical student virtual teaching COVID-19, virtual undergraduate medical education, and virtual medical education COVID-19, in the electronic databases of PubMed and Google Scholar. A total of 201 articles were found, of which 34 were included in the study. Manual searches of the reference lists of the included articles yielded 5 additional articles. The findings were tabulated and assessed under the following headings: summary of virtual teaching offered, strengths of virtual teaching, and weaknesses of virtual teaching. RESULTS: The strengths of virtual teaching included the variety of web-based resources available. New interactive forms of virtual teaching are being developed to enable students to interact with patients from their homes. Open-access teaching with medical experts has enabled students to remain abreast of the latest medical advancements and to reclaim knowledge lost by the suspension of university classes and clinical attachments. Peer mentoring has been proven to be a valuable tool for medical students with aims of increasing knowledge and providing psychological support. Weaknesses of virtual teaching included technical challenges, confidentiality issues, reduced student engagement, and loss of assessments. The mental well-being of students was found to be negatively affected during the pandemic. Inequalities of virtual teaching services worldwide were also noted to cause differences in medical education. CONCLUSIONS: In the unprecedented times of the COVID-19 pandemic, medical schools have a duty to provide ongoing education to medical students. The continuation of teaching is crucial to enable the graduation of future physicians into society. The evidence suggests that virtual teaching is effective, and institutions are working to further develop these resources to improve student engagement and interactivity. Moving forward, medical faculties must adopt a more holistic approach to student education and consider the mental impact of COVID-19 on students as well as improve the security and technology of virtual platforms.

5.
Emerg Microbes Infect ; 9(1): 221-236, 2020.
Article in English | MEDLINE | ID: covidwho-1169480

ABSTRACT

A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral , Pneumonia, Viral/virology , Amino Acid Sequence , Betacoronavirus/isolation & purification , COVID-19 , China , Humans , Phylogeny , SARS-CoV-2 , Sequence Analysis, Protein , Travel , Viral Proteins/chemistry , Viral Proteins/genetics
6.
Clin Infect Dis ; 71(16): 2150-2157, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1153175

ABSTRACT

BACKGROUND: Thymosin alpha 1 (Tα1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and the mechanism of Tα1 treatment for COVID-19 patients are still unclear. METHODS: We retrospectively reviewed the clinical outcomes of 76 severe COVID-19 cases admitted to 2 hospitals in Wuhan, China, from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells from COVID-19 patients was measured by T-cell receptor excision circles (TRECs). The levels of T-cell exhaustion markers programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) on CD8+ T cells were detected by flow cytometry. RESULTS: Compared with the untreated group, Tα1 treatment significantly reduced the mortality of severe COVID-19 patients (11.11% vs 30.00%, P = .044). Tα1 enhanced blood T-cell numbers in COVID-19 patients with severe lymphocytopenia. Under such conditions, Tα1 also successfully restored CD8+ and CD4+ T-cell numbers in elderly patients. Meanwhile, Tα1 reduced PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients compared with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells were roughly parallel to the rise of TRECs. CONCLUSIONS: Tα1 treatment significantly reduced mortality of severe COVID-19 patients. COVID-19 patients with counts of CD8+ T cells or CD4+ T cells in circulation less than 400/µL or 650/µL, respectively, gained more benefits from Tα1. Tα1 reversed T-cell exhaustion and recovered immune reconstitution through promoting thymus output during severe acute respiratory syndrome-coronavirus 2 infection.


Subject(s)
COVID-19/mortality , Lymphopenia/metabolism , SARS-CoV-2/pathogenicity , Thymalfasin/metabolism , Adult , Aged , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , COVID-19/virology , Female , Humans , Male , Middle Aged , Retrospective Studies , Thymalfasin/genetics , Thymus Gland/metabolism
7.
Antioxidants (Basel) ; 9(9)2020 Sep 21.
Article in English | MEDLINE | ID: covidwho-1121263

ABSTRACT

Due to its high degree of contagiousness and like almost no other virus, SARS-CoV-2 has put the health of the world population on alert. COVID-19 can provoke an acute inflammatory process and uncontrolled oxidative stress, which predisposes one to respiratory syndrome, and in the worst case, death. Recent evidence suggests the mechanistic role of mitochondria and vitamin D in the development of COVID-19. Indeed, mitochondrial dynamics contribute to the maintenance of cellular homeostasis, and its uncoupling involves pathological situations. SARS-CoV-2 infection is associated with altered mitochondrial dynamics with consequent oxidative stress, pro-inflammatory state, cytokine production, and cell death. Furthermore, vitamin D deficiency seems to be associated with increased COVID-19 risk. In contrast, vitamin D can normalize mitochondrial dynamics, which would improve oxidative stress, pro-inflammatory state, and cytokine production. Furthermore, vitamin D reduces renin-angiotensin-aldosterone system activation and, consequently, decreases ROS generation and improves the prognosis of SARS-CoV-2 infection. Thus, the purpose of this review is to deepen the knowledge about the role of mitochondria and vitamin D directly involved in the regulation of oxidative stress and the inflammatory state in SARS-CoV-2 infection. As future prospects, evidence suggests enhancing the vitamin D levels of the world population, especially of those individuals with additional risk factors that predispose to the lethal consequences of SARS-CoV-2 infection.

8.
J Clin Invest ; 130(12): 6417-6428, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1112385

ABSTRACT

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , COVID-19/drug therapy , COVID-19/mortality , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/mortality , Aged , COVID-19/complications , Disease-Free Survival , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/etiology , Retrospective Studies , Severity of Illness Index , Survival Rate
9.
Ann Surg ; 2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-1101934

ABSTRACT

OBJECTIVE: COVID-19 can cause acute respiratory distress syndrome (ARDS) that is rapidly progressive, severe, and refractory to conventional therapies. Extracorporeal membrane oxygenation (ECMO) can be used as a supportive therapy to improve outcomes but evidence-based guidelines have not been defined. SUMMARY BACKGROUND DATA: Initial mortality rates associated with ECMO for ARDS in COVID-19 were high, leading some to believe that there was no role for ECMO in this viral illness. With more experience, outcomes have improved. The ideal candidate, timing of cannulation, and best post-cannulation management strategy, however, has not yet been defined. METHODS: We conducted a retrospective review from April 1 to July 31 2020 of the first 25 patients with COVID-19 associated ARDS placed on V-V ECMO at our institution. We analyzed the differences between survivors to hospital discharge and those who died. Modified Poisson regression was used to model adjusted risk factors for mortality. RESULTS: 44% of patients (11/25) survived to hospital discharge. Survivors were significantly younger (40.5 years vs. 53.1 years; p < 0.001) with no differences between cohorts in mean body mass index, diabetes, or PaO2:FiO2 at cannulation. Survivors had shorter duration from symptom onset to cannulation (12.5 days vs. 19.9 days, p = 0.028) and shorter duration of intensive care unit (ICU) length of stay (LOS) prior to cannulation (5.6 days vs. 11.7 days, p = 0.045). Each day from ICU admission to cannulation increased the adjusted risk of death by 4% and each year increase in age increased the adjusted risk 6%. CONCLUSIONS: ECMO has a role in severe, refractory ARDS associated with COVID-19. Increasing age and time from ICU admission were risk factors for mortality and should be considered in patient selection. Further studies are needed to define best practices for V-V ECMO use in COVID-19.

10.
Front Immunol ; 11: 621735, 2020.
Article in English | MEDLINE | ID: covidwho-1083600

ABSTRACT

In late December 2019, multiple atypical pneumonia cases resulted in severe acute respiratory syndrome caused by a pathogen identified as a novel coronavirus SARS-CoV-2. The most common coronavirus disease 2019 (COVID-19) symptoms are pneumonia, fever, dry cough, and fatigue. However, some neurological complications following SARS-CoV-2 infection include confusion, cerebrovascular diseases, ataxia, hypogeusia, hyposmia, neuralgia, and seizures. Indeed, a growing literature demonstrates that neurotropism is a common feature of coronaviruses; therefore, the infection mechanisms already described in other coronaviruses may also be applicable for SARS-CoV-2. Understanding the underlying pathogenetic mechanisms in the nervous system infection and the neurological involvement is essential to assess possible long-term neurological alteration of COVID-19. Here, we provide an overview of associated literature regarding possible routes of COVID-19 neuroinvasion, such as the trans-synapse-connected route in the olfactory pathway and peripheral nerve terminals and its neurological implications in the central nervous system.


Subject(s)
COVID-19/virology , Nervous System/virology , SARS-CoV-2/pathogenicity , Animals , Humans
11.
Ann Surg ; 272(6): e311-e315, 2020 12.
Article in English | MEDLINE | ID: covidwho-1081376

ABSTRACT

OBJECTIVE: The aim of this study was to define whether rapidly reallocating health care workers not experienced with PP for performing PP in ICU is feasible and safe. SUMMARY BACKGROUND DATA: In the setting of severe acute respiratory distress syndrome (ARDS), the use of prone and supine positioning procedures (PP) has been associated with improved oxygenation resulting in decreased mortality. Nevertheless, applying PP is time consuming for ICU staffs that are at risk of mental of physical exhaustion, especially with the constant surge of admitted COVID-19 patients with severe ARDS. METHODS: This prospective cohort study conducted at a single regional university hospital between March 27 and April 15, 2020. Among 117 patients admitted to ICU, 67 patients (57.3%) presented with proven SARS-CoV-2 infection with severe ARDS requiring PP. After accelerated simulation training, 109 volunteers including surgeons, physicians, nurses and physiotherapists, multiple dedicated teams performed daily multiple PP following a systematic checklist. Patient demographics and PP data were collected. Patient safety and health care workers safety were assessed. RESULTS: Among 117 patients admitted to ICU, 67 patients (57.3%) required PP. Overall, 53 (79%) were male, with a median age of 68.5 years and median body mass index of 29.3 kg/m. A total of 384 PP were performed. Overall, complication occurred in 34 PP (8.8%) and led to PP cancelation in 4 patients (1%). Regarding health care workers safety, four health care workers presented with potential COVID-19 related symptoms and none was positive. CONCLUSIONS: To overcome the surge of critically ill COVID-19 patients, reallocating health care workers to targeted medical tasks beyond their respective expertise such as PP was safe.


Subject(s)
COVID-19/complications , Health Workforce/organization & administration , Patient Positioning/methods , Prone Position , SARS-CoV-2 , Severe Acute Respiratory Syndrome/therapy , Severe Acute Respiratory Syndrome/virology , Surgical Procedures, Operative , Aged , COVID-19/epidemiology , Checklist , Disease Outbreaks , Female , Humans , Male , Middle Aged , Prospective Studies , Resource Allocation/methods , Resource Allocation/organization & administration
12.
An Sist Sanit Navar ; 43(2): 251-254, 2020 Aug 31.
Article in Spanish | MEDLINE | ID: covidwho-1080494

ABSTRACT

Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses for, at least, the most severely ill patients; this practice is not free of risks, which is why only thromboembolic prophylaxis is recommended by other consensuses. In the case of previously anticoagulated patients, changing the oral anticoagulant for a low molecular weight heparin (LMWH) is generally recommended. We present the cases of two patients admitted due to COVID-19, without serious clinical data, in whom anticoagulation (acenocoumarol and rivaroxaban, respectively) was replaced by LMWH at therapeutic doses, both presenting abdominal bleeding. This type of bleeding is an infrequent complication in anticoagulated patients, but the concurrence of two cases in a short period of time in the context of the COVID-19 pandemic leads us to consider that there is not yet any clear evidence on therapeutic anticoagulation in SARS-CoV-2 infection.


Subject(s)
Anticoagulants/adverse effects , Betacoronavirus , Coronavirus Infections/complications , Hematoma/chemically induced , Pneumonia, Viral/complications , Venous Thromboembolism/prevention & control , Venous Thromboembolism/virology , Abdomen , Acenocoumarol/adverse effects , Acenocoumarol/therapeutic use , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19 , Female , Hematoma/diagnosis , Heparin, Low-Molecular-Weight/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pandemics , Rivaroxaban/adverse effects , Rivaroxaban/therapeutic use , SARS-CoV-2 , Venous Thromboembolism/drug therapy
13.
Front Med (Lausanne) ; 7: 603943, 2020.
Article in English | MEDLINE | ID: covidwho-1069726

ABSTRACT

Background: Patients with coronavirus disease 2019 (COVID-19) may develop severe acute respiratory distress syndrome (ARDS). The aim of the study was to explore the lung recruitability, individualized positive end-expiratory pressure (PEEP), and prone position in COVID-19-associated severe ARDS. Methods: Twenty patients who met the inclusion criteria were studied retrospectively (PaO2/FiO2 68.0 ± 10.3 mmHg). The patients were ventilated under volume-controlled mode with tidal volume of 6 mL/kg predicted body weight. The lung recruitability was assessed via the improvement of PaO2, PaCO2, and static respiratory system compliance (Cstat) from low to high PEEP (5-15 cmH2O). Patients were considered recruitable if two out of three parameters improved. Subsequently, PEEP was titrated according to the best Cstat. The patients were turned to prone position for further 18-20 h. Results: For recruitability assessment, average value of PaO2 was slightly improved at PEEP 15 cmH2O (68.0 ± 10.3 vs. 69.7 ± 7.9 mmHg, baseline vs. PEEP 15 cmH2O; p = 0.31). However, both PaCO2 and Cstat worsened (PaCO2: 72.5 ± 7.1 vs. 75.1 ± 9.0 mmHg; p < 0.01. Cstat: 17.5 ± 3.5 vs. 16.6 ± 3.9 ml/cmH2O; p = 0.05). Only four patients (20%) were considered lung recruitable. Individually titrated PEEP was higher than the baseline PEEP (8.0 ± 2.1 cmH2O vs. 5 cmH2O, p < 0.001). After 18-20 h of prone positioning, investigated parameters were significantly improved compared to the baseline (PaO2: 82.4 ± 15.5 mmHg. PaCO2: 67.2 ± 6.4 mmHg. Cstat: 20.6 ± 4.4 ml/cmH2O. All p < 0.001 vs. baseline). Conclusions: Lung recruitability was very low in COVID-19-associated severe ARDS. Individually titrated PEEP and prone positioning might improve lung mechanics and blood gasses.

14.
Cancer Biol Med ; 17(3): 519-527, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-1068173

ABSTRACT

A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the world, prompting the World Health Organization to declare the coronavirus disease of 2019 (COVID-19) a public health emergency of international concern. Cancer patients are regarded as a highly vulnerable population to SARS-CoV-2 infection and development of more severe COVID-19 symptoms, which is possibly due to the systemic immunosuppressive state caused directly by tumor growth and indirectly by effects of anticancer treatment. Currently, much effort has been directed toward studying the pathogenesis and treatment of COVID-19, but the risk profiles, prognoses, and treatment outcomes in cancer patients remain unclear. Based on the current literature, we summarize the risk profiles, clinical and biochemical characteristics, and therapy outcomes of COVID-19 infections in cancer patients. The challenges in the clinical care of cancer patients with COVID-19 are discussed. The goal of this review is to stimulate research to better understand the biological impact and prognoses of COVID-19 infections in cancer patients, thus facilitating improvement of the clinical management of these patients.


Subject(s)
COVID-19/complications , COVID-19/therapy , Neoplasms/complications , Neoplasms/immunology , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Disease Progression , Female , Humans , Immunization, Passive , Immunocompromised Host/immunology , Immunoglobulins, Intravenous/therapeutic use , Male , Neoplasms/therapy , Neoplasms/virology , Oxygen/therapeutic use , Prognosis , Risk Assessment , Risk Factors , SARS-CoV-2/genetics , Severity of Illness Index
15.
iScience ; 23(10): 101585, 2020 Oct 23.
Article in English | MEDLINE | ID: covidwho-1065229

ABSTRACT

In a published case-control study (GSE152075) from SARS-CoV-2-positive (n = 403) and -negative patients (n = 50), we analyzed the response to infection assessing gene expression of host cell receptors and antiviral proteins. The expression analysis associated with reported risk factors for COVID-19 was also assessed. SARS-CoV-2 cases had higher ACE2, but lower TMPRSS2, BSG/CD147, and CTSB expression compared with negative cases. COVID-19 patients' age negatively affected ACE2 expression. MX1 and MX2 were higher in COVID-19 patients. A negative trend for MX1 and MX2 was observed as patients' age increased. Principal-component analysis determined that ACE2, MX1, MX2, and BSG/CD147 expression was able to cluster non-COVID-19 and COVID-19 individuals. Multivariable regression showed that MX1 expression significantly increased for each unit of viral load increment. Altogether, these findings support differences in ACE2, MX1, MX2, and BSG/CD147 expression between COVID-19 and non-COVID-19 patients and point out to MX1 as a critical responder in SARS-CoV-2 infection.

16.
Neonatology ; 117(5): 592-598, 2020.
Article in English | MEDLINE | ID: covidwho-1059604

ABSTRACT

BACKGROUND: COVID-19 has spread rapidly over the world. Little is known about the outcomes of infections in pregnant women. The management and characteristics of preterm infants born to COVID-19 mothers need to be clarified. METHODS: In this retrospective, single-center cohort study, we describe the clinical courses of 6 preterm infants born to COVID-19 mothers, the management protocol, and related outcomes. RESULTS: Six preterm infants were admitted to Tongji Hospital between January 23 and March 19, 2020. Gestational age ranged from 28+5 to 36+3 weeks. One late preterm infant was delivered early due to maternal dyspnea from COVID-19. Five infants were delivered by Caesarean section. None had perinatal asphyxia. Two infants required respiratory support due to respiratory distress syndrome and apnea of prematurity. All infants did not develop severe complications of prematurity and are negative for severe acute respiratory syndrome (SARS)-CoV-2 nucleic acid testing. CONCLUSION: With an expedited and adequate delivery protocol, less invasive treatment principle, and active infection precautious, we found a limited impact of COVID-19 mothers on preterm delivery and neonatal short-term outcomes. The risk of vertical transmission of SARS-CoV-2 is low in preterm infants born to COVID-19 mothers if appropriate management is implemented.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Infant, Premature , Infectious Disease Transmission, Vertical , Maternal Exposure , Pregnancy Complications, Infectious/therapy , Pregnant Women , Adult , China/epidemiology , Cohort Studies , Female , Humans , Infant, Newborn , Male , Pregnancy , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
17.
J Clin Transl Res ; 6(4): 187-189, 2020 Nov 15.
Article in English | MEDLINE | ID: covidwho-1049417

ABSTRACT

Severe acute respiratory syndrome (SARS) is a fatal respiratory illness caused by the coronavirus (CoV). The first known case was reported in 2002, later coined as SARS-CoV. Over the last two decades, the CoV has periodically emerged in the general population, causing a varying degree of pneumonia. The most recent outbreak, now known as coronavirus disease of 2019 (COVID-19), has been on an exponential rise. Similar to its predecessors, COVID-19 causes a fatal form of pneumonia; however, in a small percentage of patients, COVID-19 has shown to cause neurological symptoms. Given that SARS-CoV and the new CoV strain share similar viral structures, COVID-19 may have the capability to invade the neurological system. We present a series of patients with COVID-19, the first of which presented with a seizure, whereas our second patient developed seizures during their hospital course. Neither patient had a previous history of epilepsy. Relevance for patients: COVID-19 has rapidly evolved since it was first reported and has proven to be a fatal infective process. The last several months have been challenging for the medical community as we try to understand the complexities of this virus. Clinicians have attempted to assess the most common presenting symptoms based on reported cases. The purpose of this study was to help understand how COVID-19 presents itself when the neurological system is involved. This case series describes the common and uncommon neurological manifestations of COVID-19. By doing so, we hope to provide clinicians with additional information to help diagnose COVID-19 in this unprecedented time and to also be wary of the uncommon presenting features.

18.
Cardiovasc Res ; 116(14): 2207-2215, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1048209

ABSTRACT

AIMS: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality. It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection. METHODS AND RESULTS: Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression. Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections. SARS-CoV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Coronavirus particles were further observed in cardiomyocytes of a patient with coronavirus disease 2019. Infection of induced pluripotent stem cell-derived cardiomyocytes was dependent on cathepsins and angiotensin-converting enzyme 2, and was blocked by remdesivir. CONCLUSION: This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an angiotensin-converting enzyme 2- and cathepsin-dependent manner. SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.


Subject(s)
Apoptosis , COVID-19/virology , Heart Diseases/virology , Myocytes, Cardiac/virology , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/pharmacology , Apoptosis/drug effects , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/pathology , Caco-2 Cells , Cathepsins/metabolism , Heart Diseases/drug therapy , Heart Diseases/metabolism , Heart Diseases/pathology , Host-Pathogen Interactions , Humans , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Reactive Oxygen Species/metabolism , SARS-CoV-2/drug effects , Signal Transduction
19.
Viruses ; 13(1)2020 12 25.
Article in English | MEDLINE | ID: covidwho-1043520

ABSTRACT

Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4+ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8+ regulatory T cells, the highest levels of CD56+CD16- NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence.


Subject(s)
Antibodies, Viral/blood , COVID-19/therapy , Plasma/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , B-Lymphocytes , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/immunology , Female , Humans , Immunity, Humoral , Immunization, Passive , Male , Middle Aged , Th1 Cells , Th17 Cells , Th2 Cells , Time Factors , Young Adult
20.
Cureus ; 12(12): e12290, 2020 Dec 26.
Article in English | MEDLINE | ID: covidwho-1029534

ABSTRACT

Introduction Cytokine release syndrome in COVID-19 is characterized by hyperinflammation, which manifests as acute respiratory distress syndrome (ARDS), multiorgan failure, and high inflammatory parameters. Tocilizumab, an interleukin 6 (IL-6) antagonist has been used in COVID-19 ARDS with conflicting results from different parts of the world. Objective To study the treatment outcomes with tocilizumab in patients with COVID-19 ARDS and hyperinflammation using the World Health Organization (WHO) COVID-19 ordinal scale. Methods An observational study was conducted from Feb 2020 to May 2020 on COVID-19 ARDS patients with hyperinflammation. Results A total of 244 patients with COVID-19 were admitted, out of which 107 had ARDS. Thirty patients had both ARDS and hyperinflammation and received tocilizumab. The mean age was 62.5 years (SD: 13.5) and the majority were male (83%). The mean CRP pre-treatment was 217.5 mg/L and post 48 to 72 hours of tocilizumab treatment was 98.5 mg/L. Twenty-one patients (70%) also received concomitant intravenous (IV) methylprednisolone. Of the 30 patients, seven died and 20 recovered. Ten patients required intensive care unit admission and nine developed nosocomial infections. COVID-19-associated aspergillosis was diagnosed in three patients post tocilizumab treatment. Mortality was significantly higher in patients who developed a nosocomial infection and who required intermittent positive pressure ventilation (IPPV). Post-treatment, clinical improvement was observed in patients who had a median score of 5 on the WHO ordinal scale. Conclusion Our study supports the use of tocilizumab in COVID-19 ARDS patients with a pre-treatment median WHO ordinal severity score of 5 and recommends the monitoring of nosocomial infections and opportunistic infections.

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