Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (130)

Fever (123)

Cough (101)

Hypertension (76)

Fatigue (46)


Transmission

Seroprevalence
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    COVID-19: Role of the Interferons

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

    id:202008.0018/v1 Date: 2020-08-02 Source: Preprints.org

    COVID-19 disease MESHD, caused by the SARS-CoV2 virus, is a potentially fatal disease MESHD that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia MESHD pneumonia HP in humans. ARDS is the leading cause of death MESHD in COVID-19 disease MESHD. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease MESHD is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure MESHD may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases MESHD, closely related to COVID-19 disease MESHD, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

    Impact of tocilizumab administration on mortality in severe COVID-19

    Authors: Andrew Tsai; Oumou Diawara; Ronald G Nahass; Luigi Brunetti

    doi:10.1101/2020.07.30.20114959 Date: 2020-08-02 Source: medRxiv

    Background The novel coronavirus disease MESHD 2019 (COVID-19) worldwide pandemic has placed a significant burden on hospitals and healthcare providers. The immune response to this disease MESHD is thought to lead to a cytokine storm, which contributes to the severity of illness. There is an urgent need to confirm whether the use of tocilizumab provides a benefit in individuals with COVID-19. Methods A single-center propensity-score matched cohort study, including all consecutive COVID-19 patients, admitted to the medical center who were either discharged from the medical center or expired between March 1, 2020, and May 5, 2020, was performed. Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The primary outcome was in-hospital mortality. Results A total of 132 patients were included in the matched dataset (tocilizumab=66; standard of care=66). Approximately 73% of the patients were male TRANS. Hypertension MESHD Hypertension HP (55%), diabetes mellitus MESHD diabetes mellitus HP (31%), and chronic pulmonary disease MESHD (15%) were the most common comorbidities present. There were 18 deaths MESHD (27.3%) in the tocilizumab group and 18 deaths MESHD (27.3%) in the standard of care group (odds ratio, 1.0; 95% confidence interval, 0.465 - 2.151; p=1.00). Advanced age TRANS, history of myocardial infarction MESHD myocardial infarction HP, dementia MESHD dementia HP, chronic pulmonary disease, heart MESHD failure, and malignancy were significantly more common in patients who died. Interpretation The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. Use of this therapeutic agent should be limited to the context of a clinical trial until more evidence is available.

    Augmentation of anti-MDA5 antibody SERO implies severe disease MESHD in COVID-19 patients

    Authors: Changzheng Liu; Qian Wang; Yeming Wang; Geng Wang; Linghang Wang; Hong Chen; Tao Jiao; Chaojun Hu; Xiaobo Lei; Li Guo; Lili Ren; Mengtao Li; Xiaofeng Zeng; Dingyu Zhang; Bin Cao; Jianwei Wang

    doi:10.1101/2020.07.29.20164780 Date: 2020-08-01 Source: medRxiv

    Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV2) infection MESHD, which is associated with high mortality of coronavirus disease MESHD 2019 (COVID-19). Striking similarities has been noted between COVID-19 and anti- melanoma MESHD melanoma HP differentiation-associated gene 5 (MDA5) antibody SERO (Ab)-related dermatomyositis MESHD (DM), implying a shared autoinflammatory aberrance. However, it is unclear whether anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Here, we found that the positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% and the anti-MDA5 Ab positive patients tended to develop severe disease MESHD (88.6% vs 66.9%, P<0.0001). In particular, the titer of anti-MDA5 Ab was increased in the non-survivals (5.95{+/-}5.16 vs 8.22{+/-}6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab ([≥]10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Overall, our data reveal that anti-MDA5 Ab is prevalent in the COVID-19 patients and high titer of this antibody SERO is correlated with severe disease MESHD and unfavorable outcomes.

    High rate of major drug-drug interactions of lopinavir-ritonavir for COVID-19 treatment

    Authors: Juan Macias; Ana Pinilla; Francisco A Lao-Dominguez; Anais Corma; Enrique Contreras-Macias; Alejandro Gonzalez-Serna; Antonio Gutierrez-Pizarraya; Marta Fernandez-Fuertes; Ramon Morillo-Verdugo; Marta Trigo; Luis M Real; Juan A Pineda

    doi:10.1101/2020.07.30.20165027 Date: 2020-08-01 Source: medRxiv

    The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease MESHD 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection MESHD treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI: 69%-85%) patients, and in 33 (26%, 95% CI: 19%-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p=0.010). After adjustment, only the Charlson index was independently associated with death MESHD [adjusted OR (95% CI) for Charlson index [≥]5: 85 (10-731), p <0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases MESHD Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p=0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age TRANS and comorbidities. Patients managed by the Infectious Diseases MESHD Unit had lower risk of major DDI.

    Persistence of anti- SARS-CoV-2 antibodies SERO in non-hospitalized COVID-19 convalescent health care workers

    Authors: Margherita Bruni; Valentina Cecatiello; Angelica Diaz-Basabe; Georgia Lattanzi; Erika Mileti; Silvia Monzani; Laura Pirovano; Francesca Rizzelli; Clara Visintin; Giuseppina Bonizzi; Marco Giani; Marialuisa Lavitrano; Silvia Faravelli; Federico Forneris; Flavio Caprioli; Pier Giuseppe Pelicci; Gioacchino Natoli; Sebastiano Pasqualato; Marina Mapelli; Federica Facciotti

    doi:10.1101/2020.07.30.20164368 Date: 2020-08-01 Source: medRxiv

    Background. Coronavirus disease MESHD-19 (COVID-19) is a respiratory illness caused by the Severe Acute Respiratory Syndrome MESHD CoronaVirus 2 (SARS-CoV-2), a novel beta-coronavirus. Although antibody SERO response to SARS-CoV-2 can be detected early during the infection MESHD, several outstanding questions remain to be addressed regarding magnitude and persistence of antibody SERO titer against different viral proteins and their correlation with the strength of the immune response, as measured by serum SERO levels of pro-inflammatory mediators. Methods. An ELISA assay SERO has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length nucleocapsid protein (N protein). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies SERO as well as soluble pro-inflammatory mediators in the sera. Results. Specificity and sensitivity SERO of the ELISA assays SERO were high for anti-RBD IgG and IgA (92-97%) and slightly lower for IgM and the Spike and N proteins (70-85%). The ELISA SERO allowed quantification of IgM, IgG and IgA antibody SERO responses against all the viral antigens tested and showed a correlation between magnitude of the antibody SERO response and disease MESHD severity. Non-hospitalized subjects showed lower antibody SERO titers and blood SERO pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested SERO. Noteworthy, in non-severe COVID-19 infections MESHD, antibody SERO titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Conclusions. Rapid decline in antibody SERO titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection MESHD, suggesting that antibody SERO-mediated protection against re- infection MESHD with SARS-CoV-2 is of short duration. These results suggest caution in use serological testing SERO to estimate the prevalence SERO of SARS-CoV-2 infection MESHD in the general population.

    Clinical Outcomes From COVID-19 Following Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers Among Patients with Hypertension MESHD Hypertension HP in South Korea: A nationwide study

    Authors: Ju Hwan Kim; Yeon-Hee Baek; Hyesung Lee; Young June Choe; Hyun Joon Shin; Ju-Young Shin

    doi:10.1101/2020.07.29.20164822 Date: 2020-08-01 Source: medRxiv

    There is ongoing debate as to whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) use is associated with poor prognosis of coronavirus disease MESHD-2019 (COVID-19). We sought to investigate the association between ACEI/ARB use and risk of poor clinical outcomes from COVID-19. We identified 1,290 patients with hypertension MESHD hypertension HP, of which 682 had recorded ACEI/ARB use and 608 without the use during 30 days preceding the date of COVID-19 diagnosis in completely enumerated COVID-19 cohort in South Korea. Our primary endpoint was the clinical outcomes comprised of all-cause mortality, use of mechanical ventilation, intensive care unit (ICU) admission, and sepsis MESHD sepsis HP. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and Poisson regression model to estimate the relative risks (RR) and 95% confidence intervals (CI) to compare outcomes in ACEI/ARB users with non-users. Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW adjusted RR, 0.60; 95% CI, 0.42-0.85; p=0.0046). When assessed by individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW adjusted RR, 0.62; 95% CI, 0.35-1.09; p=0.0973) and respiratory events (IPTW adjusted RR, 0.99; 95% CI, 0.84-1.17; p=0.9043). Subgroup analysis showed a trend toward protective role of ACEIs and ARBs against overall outcomes in men (IPTW adjusted RR, 0.84; 95% CI, 0.69-1.03; p-for-interaction=0.008) and with pre-existing respiratory disease MESHD (IPTW adjusted RR, 0.74; 95% CI, 0.60-0.92; p-for-interaction=0.0023). We present clinical evidence to support continuing ACE/ARB use in completely enumerated hypertensive COVID-19 cohort in South Korea.

    Use of a humanized anti-CD6 monoclonal antibody SERO (itolizumab) in elderly TRANS patients with moderate COVID-19

    Authors: Mayra Ramos-Suzarte; Yayquier Diaz; Yordanis Martin; Nestor Antonio Calderon; William Santiago; Orlando Vinet; Yulieski La O; Jorge Perez; Augusto Oyarzabal; Yoan Perez; Geidy Lorenzo; Meylan Cepeda; Danay Saavedra; Zayma Mazorra; Daymys Estevez; Patricia Lorenzo-Luaces; Carmen Valenzuela; Armando Caballero; Kalet leon; Tania Crombet; Carlos Jorge Hidalgo

    doi:10.1101/2020.07.24.20153833 Date: 2020-07-30 Source: medRxiv

    Abstract Introduction: The Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease MESHD (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11. Elderly TRANS with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection MESHD. During the outbreak, a local transmission TRANS event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly TRANS residents were positive for SARS-CoV-2. Methods: Based on the increased susceptibility to viral-induced cytokine release syndrome MESHD inducing respiratory and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody SERO. Results: All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease MESHD was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age TRANS, comorbidities and severity of the disease MESHD. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented. Discussion/Conclusion: Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 serum SERO levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death MESHD. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease MESHD worsening and mortality. The humanized antibody SERO itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome MESHD from other pathologies.

    Association between Alzheimer's disease MESHD and COVID-19: A bidirectional Mendelian randomization

    Authors: Di Liu; Xiaoyu Zhang; Weijie Cao; Jie Zhang; Manshu Song; Weijia Xing; Wei Wang; Qun Meng; Youxin Wang

    doi:10.1101/2020.07.27.20163212 Date: 2020-07-30 Source: medRxiv

    Background In observational studies, Alzheimer's disease MESHD (AD) has been associated with an increased risk of Coronavirus disease MESHD 2019 (COVID-19), and the prognosis of COVID-19 can affect nervous systems. However, the causality between these conditions remains to be determined. Methods This study sought to investigate the bidirectional causal relations of AD with COVID-19 using two-sample Mendelian randomization (MR) analysis. Results We found that genetically predicted AD was significantly associated with higher risk of severe COVID-19 (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.139-9.725; P=0.028). It's interesting that genetically predicted severe COVID-19 was also significantly associated with higher risk of AD (OR, 1.004; 95% CI, 1.001-1.007; P=0.018). In addition, the two strong genetic variants associated with severe COVID-19 was associated with higher AD risk (OR, 1.018; 95% CI, 1.003-1.034; P=0.018). There is no evidence to support that genetically predicted AD was significantly associated with COVID-19 susceptibility, and vice versa. No obvious pleiotropy bias and heterogeneity were observed. Conclusion Overall, AD may causally affect severe COVID-19, and vice versa, performing bidirectional regulation through independent biological pathways.

    Descriptive epidemiology of 16,780 hospitalized COVID-19 patients in the United States

    Authors: Shemra Rizzo; Devika Chawla; Kelly Zalocusky; Daniel Keebler; Jenny Chia; Lisa Lindsay; Vincent Yau; Tripthi Kamath; Larry Tsai

    doi:10.1101/2020.07.17.20156265 Date: 2020-07-29 Source: medRxiv

    BACKGROUND: Despite the significant morbidity and mortality caused by the 2019 novel coronavirus disease MESHD (COVID-19), our understanding of basic disease MESHD epidemiology remains limited. This study aimed to describe key patient characteristics, comorbidities, treatments, and outcomes of a large U.S.-based cohort of patients hospitalized with COVD-19 using electronic health records (EHR). METHODS: We identified patients in the Optum De-identified COVID-19 EHR database who had laboratory-confirmed COVID-19 or a presumptive diagnosis between 20 February 2020 and 6 June 2020. We included hospitalizations that occurred 7 days prior to, or within 21 days after, COVID-19 diagnosis. Among hospitalized patients we describe the following: vital statistics and laboratory results on admission, relevant comorbidities (using diagnostic, procedural, and revenue codes), medications (NDC, HCPC codes), ventilation, intensive care unit (ICU) stay, length of stay (LOS), and mortality. RESULTS: We identified 76,819 patients diagnosed with COVID-19, 16,780 of whom met inclusion criteria for COVID-related hospitalization. Over half the cohort was over age TRANS 50 (74.5%), overweight MESHD overweight HP or obese (77.2%), or had hypertension MESHD hypertension HP (58.1%). At admission, 30.3% of patients presented with fever MESHD fever HP (>38C) and 32.3% had low oxygen saturation (<90%). Among the 16,099 patients with complete hospital records, we observed that 58.9% had hypoxia MESHD, 23.4% had an ICU stay during hospitalization, 18.1% were ventilated, and 16.2% died. The median LOS was 6 days (IQR: 4, 11). CONCLUSIONS: To our knowledge, this is the largest descriptive study of patients hospitalized with COVID-19 in the United States. We report summary statistics of key clinical outcomes that provide insights to better understand COVID-19 disease MESHD epidemiology.

    Whence the next pandemic? The intersecting global geography of the animal-human interface, poor health systems and air transit centrality reveals conduits for high-impact spillover

    Authors: Michael G Walsh; Shailendra Sawleshwarkar; Shah Hossain; Siobhan Mor

    doi:10.1101/2020.07.27.20163196 Date: 2020-07-29 Source: medRxiv

    The health and economic impacts of infectious disease MESHD pandemics are catastrophic as most recently manifested by coronavirus disease MESHD 2019 (COVID-19). The emerging infections MESHD that lead to substantive epidemics or pandemics are typically zoonoses MESHD that cross species boundaries at vulnerable points of animal-human interface. The sharing of space between wildlife and humans, and their domesticated animals, has dramatically increased in recent decades and is a key driver of pathogen spillover. Increasing animal-human interface has also occurred in concert with both increasing globalisation and failing health systems, resulting in a trifecta with dire implications for human and animal health. Nevertheless, to date we lack a geographical description of this trifecta that can be applied strategically to pandemic prevention. This investigation provides the first geographical quantification of the intersection of animal-human interfaces, poor human health system performance SERO and global connectivity via the network of air travel TRANS. In so doing, this work provides a systematic, data-driven approach to classifying spillover hazard based on the distribution of animal-human interfaces while simultaneously identifying globally connected cities that are adjacent to these interfaces and which may facilitate global pathogen dissemination. We present this geography of high-impact spillover as a tool for developing targeted surveillance systems and improved health infrastructure in vulnerable areas that may present conduits for future pandemics.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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