Corpus overview


MeSH Disease

Human Phenotype


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    Suspected Serious Adverse Drug Reactions in Hospitalized COVID-19 Patients

    Authors: Elena Ramírez; Mikel Urroz; Amelia Rodríguez Mariblanca; Alberto Martín-Vega; Yuri Villán; Enrique Seco; Jaime Monserrat; Jesús Frías; Antonio J. Carcas; Alberto M. Borobia

    id:10.20944/preprints202008.0283.v1 Date: 2020-08-12 Source:

    BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients versus non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019. METHODS: All ALSs that reflected potential SADRs (including neutropenia MESHD neutropenia HP, pancytopenia MESHD pancytopenia HP, thrombocytopenia MESHD thrombocytopenia HP, anemia MESHD anemia HP, eosinophilia MESHD eosinophilia HP, leukocytes in cerebrospinal fluid, hepatitis MESHD hepatitis MESHD hepatitis HP, pancreatitis MESHD pancreatitis, acute HP, acute kidney injury MESHD, rhabdomyolysis MESHD rhabdomyolysis HP and hyponatremia MESHD hyponatremia HP were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients. RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients,95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%). CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events.

    Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

    Authors: Markus Hoffmann; Heike Hofmann-Winkler; Joan C. Smith; Nadine Krueger; Lambert K. Sorensen; Ole S. Sogaard; Jorgen Bo Hasselstrom; Michael Winkler; Tim Hempel; Lluis Raich; Simon Olsson; Takashi Yamazoe; Katsura Yamatsuta; Hirotaka Mizuno; Stephan Ludwig; Frank Noe; Jason M. Sheltzer; Mads Kjolby; Stefan Poehlmann

    doi:10.1101/2020.08.05.237651 Date: 2020-08-05 Source: bioRxiv

    Antiviral therapy is urgently needed to combat the coronavirus disease MESHD 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The protease inhibitor camostat mesylate inhibits SARS-CoV-2 infection MESHD of lung cells by blocking the virus-activating host cell protease TMPRSS2. Camostat mesylate has been approved for treatment of pancreatitis MESHD pancreatitis HP in Japan and is currently being repurposed for COVID-19 treatment. However, potential mechanisms of viral resistance as well as camostat mesylate metabolization and antiviral activity of metabolites are unclear. Here, we show that SARS-CoV-2 can employ TMPRSS2-related host cell proteases for activation and that several of them are expressed in viral target cells. However, entry mediated by these proteases was blocked by camostat mesylate. The camostat metabolite GBPA inhibited the activity of recombinant TMPRSS2 with reduced efficiency as compared to camostat mesylate and was rapidly generated in the presence of serum SERO. Importantly, the infection MESHD experiments in which camostat mesylate was identified as a SARS-CoV-2 inhibitor involved preincubation of target cells with camostat mesylate in the presence of serum SERO for 2 h and thus allowed conversion of camostat mesylate into GBPA. Indeed, when the antiviral activities of GBPA and camostat mesylate were compared in this setting, no major differences were identified. Our results indicate that use of TMPRSS2-related proteases for entry into target cells will not render SARS-CoV-2 camostat mesylate resistant. Moreover, the present and previous findings suggest that the peak concentrations of GBPA established after the clinically approved camostat mesylate dose (600 mg/day) will result in antiviral activity.

    Patients with COVID-19 Interstitial Pneumonia MESHD Pneumonia HP Exhibit Pancreatic Hyperenzymemia and Not Acute Pancreatitis HP Pancreatitis MESHD

    Authors: Raffaele Pezzilli; Stefano Centanni; Michele Mondoni; Rocco F. Rinaldo; Matteo Davì; Rossana Stefanelli; GianVico Melzi d’Eril; Alessandra Barassi

    doi:10.21203/ Date: 2020-07-28 Source: ResearchSquare

    Background and aims: Gastrointestinal manifestations of COVID-19 have been well established, but pancreatic involvement is under debate. The aim of the study is to evaluate the presence of acute pancreatitis HP pancreatitis MESHD in COVID-19 patients and to assess the frequency of pancreatic hyperenzymemia. Methods: From April 1st 2020 to April 30th 2020, 110 consecutive patients (69 males TRANS, 41 females TRANS; mean age TRANS 63.0 years, range 24-93 years) met these criteria and were enrolled in the study.. The clinical data and serum SERO activity of pancreatic amylase and lipase were assayed in all patients using commercially available kits. Results: None of the patients studied developed clinical signs or morphological alterations compatible with acute pancreatitis HP pancreatitis MESHD. However, it was found that 24.5% of the patients had amylase values above 53 IU/L and 16.4% had lipase values above 300 IU/. Only one patient (0.9%) had both amylase and lipase values in excess of three-fold the upper normal limit without clinical signs of pancreatitis MESHD pancreatitis HP. Conclusions: The presence of pancreatic hyperenzymemia in a patient with COVID-19 requires the management of these patients be guided by clinical evaluation and not merely by evaluation of the biochemical results.

    COVID-19, What Could Sepsis MESHD Sepsis HP, Severe Acute Pancreatitis HP Pancreatitis MESHD, Gender TRANS Differences and Aging Teach Us?

    Authors: Claudio Gallo; Sirio Fiorino; Giovanni Posabella; Donato Antonacci; Antonio Tropeano; Emanuele Pausini; Carlotta Pausini; Tommaso Guarniero; Marco Zancanaro

    id:202007.0414/v1 Date: 2020-07-19 Source:

    Severe COVID-19 disease MESHD is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis MESHD sepsis HP is characterised by an exaggerated inflammatory response, called SIRS ( Systemic Inflammatory Response Syndrome MESHD), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome MESHD). Clinical studies reveal that most sepsis MESHD sepsis HP patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis HP pancreatitis MESHD begins with local inflammation MESHD that induces systemic inflammatory response syndrome MESHD (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease MESHD, the male TRANS response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male TRANS sex tends to have a more robust hyper inflammatory response than the female TRANS one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis MESHD Sepsis HP, severe acute pancreatitis HP pancreatitis MESHD and COVID-19 disease MESHD evolve between two fundamental aspects: hyper inflammation MESHD and immunodepression. The experience gained over years of studies of sepsis MESHD sepsis HP and severe acute pancreatitis HP pancreatitis MESHD suggests that therapies should be differentiated according to the evolutionary stage of the disease MESHD. The goal is to save the lives of most patients with COVID-19 disease MESHD. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease MESHD, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease MESHD) personalized, (based on sex, co-morbidities, age TRANS, etc.) and timely (based on signs, symptoms MESHD, laboratory parameters and instrumental investigations).

    Acute pancreatitis HP pancreatitis MESHD following treatment with protease inhibitors, which may be potential therapeutics for COVID-19: A real-world analysis of postmarketing surveillance data

    Authors: Lei Zhang; Bin Zhao; Yongguang Shang; Wangjun Qin

    doi:10.21203/ Date: 2020-05-28 Source: ResearchSquare

    Backgrounds: The potential therapeutic effects of protease inhibitors (PIs), such as lopinavir/ritonavir and darunavir, on COVID-19 are being tested in clinical trials. Although acute pancreatitis HP pancreatitis MESHD (AP) has been reported in patients treated with PIs, there have been few real-world studies comparing the occurrence and characteristics of AP after different PI regimens. Methods: Disproportionality analysis and Bayesian analysis were utilized for data mining of the Food and Drug Administration's Adverse Event Reporting System (FAERS) database for suspected adverse events involving AP after PI from January 2004 to December 2019. The times to onset and fatality rates of AP following different PI regimens were also compared. Results: Based on 33,832 reports related to PIs, 285 cases (0.84% of total adverse drug reactions, ADRs) were associated with AP; in these reports, the number of AP cases reported for the top five PIs was as follows: ritonavir/dasabuvir/ombitasvir/paritaprevir, 64 (22.46%); ritonavir, 54 (18.95%); atazanavir, 52 (18.25%); lopinavir/ritonavir, 48 (16.84%); and darunavir, 26 (9.12%). Twelve out of the 15 studied PIs, including lopinavir/ritonavir, darunavir and nelfinavir, which are potential therapeutics for COVID-19, were associated with AP. Of all the reported adverse events involving AP related to PIs, 64.56% occurred in men, which was a much higher proportion than what was observed in women (28.42%). The median time to onset of AP was 103 (IQR: 26-408) days after the initiation of PI treatment. Patients treated with ritonavir/dasabuvir/ombitasvir/paritaprevir appeared to have an earlier onset of AP than those receiving atazanavir (31 [IQR: 17–68.25] days vs 187.5 [IQR: 80.5–556.5] days, p=0.0379) or ritonavir (31 [IQR: 17–68.25] days vs 177 [IQR: 56–539] days, p=0.0371). Compared with AP cases induced by all studied PIs, which had a fatality rate of 14.02%, AP cases associated with ritonavir (18.87%) and lopinavir/ritonavir (22.73%) appeared to be associated with a higher risk of death MESHD. Conclusions: Analysis of the FAERS data provides a more precise understanding of the occurrence and characteristics of AP after different PI regimens. Signals for AP associated with various PI regimens have been detected. The findings support continued surveillance, risk factor identification, and comparative studies.

    Evidence for anti-viral effects of complete Freunds adjuvant in the mouse model of enterovirus infection MESHD

    Authors: Arunakumar Gangaplara; Chandirasegaran Massilamany; Ninaad Lasrado; David Steffen; Jay Reddy

    doi:10.1101/2020.05.27.120121 Date: 2020-05-28 Source: bioRxiv

    Group B Coxsackieviruses belonging to the genus, Enterovirus, contain six serotypes that induce various diseases MESHD, whose occurrence may involve the mediation of more than one serotype. We recently identified immunogenic epitopes within CVB3 viral protein 1 that induce anti-viral T cell responses in mouse models of CVB infections MESHD. In our investigations to determine the protective responses of the viral epitopes, we unexpectedly noted that animals immunized with complete Freunds adjuvant (CFA) alone and later challenged with CVB3 were completely protected against myocarditis MESHD myocarditis HP. Similarly, the pancreatitis MESHD pancreatitis HP-inducing ability of CVB3 was remarkably reduced to only 10% in the CFA group as opposed to 73.3% in the control group that received no CFA. Additionally, no mortalities were noted in the CFA group, whereas 40% of control animals died during the course of 21 days post- infection MESHD with CVB3. Taken together, our data suggest that the adjuvant effects of CFA may be sufficient for protection against CVB infections MESHD. These observations may provide new insights into our understanding of the occurrence of viral infections MESHD. One example is Coronavirus disease MESHD-19 (COVID-19) as individuals suffering from COVID-19 who have been vaccinated with Bacillus Calmette-Guerin appear to have fewer morbidities and mortalities than unvaccinated individuals.

    Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19

    Authors: Erwin Chiquete; Liz Toapanta-Yanchapaxi; Carlos Cantu-Brito

    doi:10.1101/2020.04.26.20079988 Date: 2020-05-01 Source: medRxiv

    Background: Coronavirus disease MESHD 2019 (COVID-19) is the systemic entity caused by the severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) that may cause death MESHD through severe atypical pneumonia MESHD pneumonia HP and acute lung injury MESHD. Valproic acid (VPA) has shown anti-inflammatory activity and mild intrinsic antiviral effect. These properties warrant the study of VPA as a possible active treatment in persons with severe COVID-19. Methods: Consecutive adult TRANS patients needing invasive mechanical ventilation (IMV) will be given intravenous (i.v.) VPA at a starting dose of 20 mg/kg/day and up to 60/kg/day (in 60 min i.v. infusions in 250 mL normal saline) as needed to reach plasma SERO VPA concentrations of 50-100 mcg/mL (measured every 72 h). These patients will be followed-up for 10 days for the primary outcome and for a further period of 30 days after treatment completion for the secondary outcome of recurrence MESHD. The primary study outcome is the reduction in the case fatality rate of at least 50% after 10 days of treatment (as compared with natural history). Secondary outcomes are the reduction of length of stay (LOS) of at least 50%, as well as COVID-19 recurrence MESHD at 30-day follow-up. The most important safety outcomes are acute liver failure MESHD, acute pancreatitis HP pancreatitis MESHD, and thrombocytopenia MESHD thrombocytopenia HP. Conclusion: Although long-term adverse effects MESHD and even pro-inflammatory consequences have been reported with the chronic use of VPA, given the urgent need for a drug against COVID-19 to shorten the high mortality and LOS, the study of VPA is justified from a scientific standpoint.

    Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection MESHD

    Authors: Furong Liu; Xin Long; Wenbin Zou; Minghao Fang; Wenjuan Wu; Wei Li; Bixiang Zhang; Wanguang Zhang; Xiaoping Chen; Zhanguo Zhang

    doi:10.1101/2020.02.28.20029181 Date: 2020-03-03 Source: medRxiv

    The ongoing outbreak of coronavirus disease MESHD 2019 (COVID-19) caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) started in the end of 2019 in China has triggered a global public health crisis. Previous studies have shown that SARS-CoV-2 infects cells by binding angiotensin-converting enzyme 2 (ACE2), which is the same as SARS-CoV. The expression and distribution of ACE2 in the pancreas are unknown. At the same time, the injury of pancreas after SARS-CoV-2 infection MESHD has not been concerned. Here, we collected public datasets (bulk RNA-seq and single-cell RNA-seq) to indicate the expression and the distribution of ACE2 in pancreas (in both exocrine glands and islets). And further, clinical data including mild and severe patients with COVID-19 demonstrated there existed mild pancreatitis MESHD pancreatitis HP. In the 67 severe cases, 11 patients (16.41%) showed elevated levels of both amylase and lipase, and 5 patients (7.46%) showed imaging alterations. Only one patient (1.85%) showed elevated levels of both amylase and lipase in 54 mild cases, without imaging changes. Our study revealed the phenomenon and possible cause of mild pancreatic injury in patients with COVID-19. This suggests that pancreatitis MESHD pancreatitis HP after SARS-CoV-2 infection MESHD should also be paid attention in clinical work.

    Clinical characteristics of 25 death MESHD cases infected with COVID-19 pneumonia MESHD pneumonia HP: a retrospective review of medical records in a single medical center, Wuhan, China

    Authors: Xun Li; Luwen Wang; Shaonan Yan; Fan Yang; Longkui Xiang; Jiling Zhu; Bo Shen; Zuojiong Gong

    doi:10.1101/2020.02.19.20025239 Date: 2020-02-25 Source: medRxiv

    Summary Background The pneumonia MESHD pneumonia HP caused by the 2019 novel coronavirus (SARS-CoV-2) is a highly infectious disease MESHD, which was occurred in Wuhan, Hubei Province, China in December 2019. As of February 13, 2020, a total of 59883 cases of COVID-19 in China have been confirmed and 1368 patients have died from the disease MESHD. However, the clinical characteristics of the dyed patients were still not clearly clarified. This study aims to summarize the clinical characteristics of death MESHD cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiologic assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Findings The mean age TRANS of the dead was 71.48 years, the average course of the disease MESHD was 10.56 days, all patients eventually died of respiratory failure HP. All of those who died had underlying diseases MESHD, the most common of which was hypertension MESHD hypertension HP (16/25, 64%), followed by diabetes (10/25, 40%), heart diseases MESHD (8/25, 32%), kidney diseases MESHD (5/25, 20%), cerebral infarction MESHD (4/25, 16%), chronic obstructive pulmonary disease MESHD chronic obstructive pulmonary disease HP (COPD, 2/25, 8%), malignant tumors (2/25, 8%) and acute pancreatitis HP pancreatitis MESHD (1/25, 4%). The most common organ damage outside the lungs was the heart, followed by kidney and liver. In the patients' last examination before death MESHD, white blood SERO cell and neutrophil counts were elevated in 17 patients (17/25, 68%) and 18 patients (18/25, 72%), lymphocyte counts were decreased in 22 patients (22/25, 88%). Most patients' PCT, CRP and SAA levels were elevated, the percentages were 90.5% (19/21), 85% (19/20) and 100% (21/21) respectively. The levels of the last test of neutrophils (15/16, 93.8%), PCT (11/11, 100%), CRP (11/13, 84.6%), cTnI (8/9, 88.9%), D-Dimer (11/12, 91.6%) and LDH (9/9, 100%) were increased as compared to the first test, while the levels of lymphocytes were decreased (14/16, 87.5%). Interpretation The age TRANS and underlying diseases MESHD ( hypertension MESHD hypertension HP, diabetes, etc.) were the most important risk factors for death MESHD of COVID-19 pneumonia MESHD pneumonia HP. Bacterial infections MESHD may play an important role in promoting the death MESHD of patients. Malnutrition MESHD Malnutrition HP was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-Dimer and LDH levels can be used as indicators of disease progression MESHD, as well as the decline of lymphocytes counts.

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MeSH Disease
Human Phenotype

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