Corpus overview


MeSH Disease

Human Phenotype


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    Paracetamol use in COVID-19: friend TRANS or enemy?

    Authors: Piero Sestili; Carmela Fimognari

    id:202008.0186/v1 Date: 2020-08-07 Source:

    COVID-19 pandemic represents an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease MESHD are still urgently needed.A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of initial symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention. In analogy with other respiratory viral infections MESHD, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain MESHD pain HP, fever MESHD fever HP and control inflammation MESHD. Non-steroidal antinflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in these conditions and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of ACE2 protein levels (the receptor used by SARS-CoV2 to enter host airways cells), the risk of bacterial superinfections MESHD and masking of disease MESHD symptoms. As a consequence, the use of NSAIDs was, and is, strongly discouraged while the alternative adoption of paracetamol is still preferred.On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may produce an oxidative imbalance which could be detrimental in COVID-19 clinical outcomes.

    COVIDOSE: Low-dose tocilizumab in the treatment of Covid-19

    Authors: Garth W Strohbehn; Brian L Heiss; Sherin J Rouhani; Jonathan A Trujillo; Jovian Yu; Alec J Kacew; Emily F Higgs; Jeffrey C Bloodworth; Alexandra Cabanov; Rachel C Wright; Adriana Koziol; Alexandra Weiss; Keith Danahey; Theodore G Karrison; Cuoghi C Edens; Iazsmin Bauer Ventura; Natasha N Pettit; Bhakti Patel; Jennifer Pisano; Mary E Strek; Thomas F Gajewski; Mark J Ratain; Pankti D Reid

    doi:10.1101/2020.07.20.20157503 Date: 2020-07-26 Source: medRxiv

    Background Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the high mortality of coronavirus disease MESHD 2019 (Covid-19). Tocilizumab, an IL-6 receptor blocking monoclonal antibody SERO, has been repurposed for Covid-19, but prospective trials and dose-finding studies in Covid-19 are lacking. Methods We conducted a phase 2 trial of low-dose tocilizumab in hospitalized adult TRANS patients with Covid-19, radiographic pulmonary infiltrate HP, fever MESHD fever HP, and C-reactive protein (CRP) >= 40 mg/L who did not require mechanical ventilation. Dose cohorts were determined by a trial Operations Committee, stratified by CRP and epidemiologic risk factors. A range of doses from 40 to 200 mg (low-dose tocilizumab) was evaluated, with allowance for one repeat dose at 24-48 hours. The primary objective was to assess the relationship of dose to fever MESHD fever HP resolution and CRP response. Outcomes were compared with retrospective controls with Covid-19. Correlative studies evaluating host antibody SERO response were performed in parallel. Findings A total of 32 patients received low-dose tocilizumab. This cohort had improved fever MESHD fever HP resolution (75.0% vs. 34.2%, p = 0.001) and CRP decline (86.2% vs. 14.3%, p < 0.001) in the 24-48 hours following drug administration, as compared to the retrospective controls (N=41). The probabilities of fever MESHD fever HP resolution or CRP decline did not appear to be dose-related in this small study (p=0.80 and p=0.10, respectively). Within the 28-day follow-up, 5 (15.6%) patients died. For patients who recovered, median time to clinical recovery was 3 days (IQR, 2-5). Clinically presumed and/or cultured bacterial superinfections MESHD were reported in 5 (15.6%) patients. Correlative biological studies demonstrated that tocilizumab-treated patients produced anti- SARS-CoV-2 antibodies SERO comparable to controls. Interpretation Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with Covid-19. Results of this trial and its correlative biological studies provide rationale for a randomized, controlled trial of low-dose tocilizumab in Covid-19.

    Invasive pulmonary aspergillosis MESHD Invasive pulmonary aspergillosis HP in critically ill patients with severe COVID-19 pneumonia MESHD pneumonia HP: results from the prospective AspCOVID-19 study

    Authors: Tobias Lahmer

    doi:10.1101/2020.07.21.20158972 Date: 2020-07-22 Source: medRxiv

    Background: Superinfections MESHD, including invasive pulmonary aspergillosis MESHD invasive pulmonary aspergillosis HP (IPA), are well-known complications of critically ill patients with severe viral pneumonia MESHD pneumonia HP. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia MESHD pneumonia HP. Methods: We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia MESHD pneumonia HP for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis MESHD invasive pulmonary aspergillosis HP (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from bronchial aspirates. We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls. Findings: CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia MESHD pneumonia HP as compared to 8% in the control cohort. In the COVID-19 cohort, mean age TRANS, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p=0.340) and days of mechanical ventilation (20 versus 15 days; p=0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA. Interpretation: CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis MESHD invasive pulmonary aspergillosis HP. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.

    Factors Affecting SARS-CoV-2 (COVID-19) Pandemic, including Zoonotic, Human Transmission and Chain TRANS of Infection MESHD. Reducing Public Health Risk by Serum SERO Antibody Testing SERO, Avoiding Screening in Unhygienic Places and False PCR Reporting. A Scientific Review

    Authors: Kamran Mahmood Ahmed Aziz; Abdullah Othman; Waleed Alqahtani; Sumaiya Azhar

    id:10.20944/preprints202006.0284.v1 Date: 2020-06-23 Source:

    Since December 2019, a rapid increase in the number of SARS-CoV-2 (COVID-19) cases was reported worldwide, despite strict infection MESHD control and lock down measures. Current paper investigated the actual facts behind this rapid increase in the number of cases. Study of genomic sequence reveals that domestic and wild animals were likely ancestors and zoonotic source for SARS-CoVs, MERS-CoVs, and SARS-CoV-2. Strong evidence suggest that these viruses already existed and replicated in animals and humans during past several decades, exhibiting diverse mutations, evolutions and self-limiting diseases MESHD, except during outbreaks. Serious zoonotic reservoir investigations are required to investigate animal transmission TRANS of SARS-CoVs and SARS-CoV-2 to limit current pandemic. This might be the reason of increasing number of cases via animals. SARS-CoV-2 has been retrospectively isolated in different studies in August 2019, several months before Wuhan announced. Hence, there is a possibility that viruses existed, went undetected, infecting subclinically, in past several years, and SARS-CoV-2 antigens and neutralizing antibodies SERO may have been present in humans since long time. This might be another reason of increasing number of cases by screening as mass screening and antigen or antibody testing SERO was not carried out in the past years. Randomized controlled trials are required to investigate human to human transmission TRANS by touch, as the current evidence is limited with conflicting results. As all SARS-CoVs are basically respiratory viruses, droplet precautions and infection MESHD control measures are essential, especially for hospital staff. Increased number of SARS-CoV-2 asymptomatic TRANS, or subclinical cases are detected worldwide. This silent phase of transmission TRANS can be beneficial for humans. Lack of symptoms eventually lessen virus transmission TRANS and reduce the pathogen's long-term survival and provide humoral herd immunity up to several years. Hence, seropositivity with diverse antibodies SERO develops against mutating SARS-CoVs which will confer strong immunity during epidemics. Strategies such as identification, contact tracing TRANS and quarantine are costly and practically difficult. Hence, asymptomatic TRANS persons can continue their work with droplet precautions and standard infection MESHD control procedures, while symptomatic or sick persons can isolate themselves in their homes without the need for strict quarantine until clinical recovery, with reduced hospital visits and minimizing chances of hospital acquired infections MESHD. RT-PCR has low sensitivity SERO and specificity, carries a high risk of handling live virus antigens, and requires difficult protocols. As viral load also sharply declines after few days of onset of infection MESHD, this technique might overlook infection MESHD. Furthermore, SARS-CoV-2 infection MESHD may be present in blood SERO when oropharyngeal swabs are negative by RT-PCR. Additionally, RT-PCR usually gives false negative and false positive results and must be interpreted cautiously. This might be again a reason of increasing number of cases by false positive RT-PCR reporting. Moreover, antibodies SERO against SARS-CoVs develop robustly in serum SERO even by reduced amount of antigens. In contrast to RT-PCR, ELISA SERO for diagnosing antibodies SERO against SARS-CoV-2 demonstrates 100% specificity and 100% sensitivity SERO, even in clinically asymptomatic TRANS individuals. These antibodies SERO can be used for serologic surveys SERO, monitoring and screening. However, screening tests for SARS-COV-2 should be avoided in unhygienic public places by nasopharyngeal swabs, which carry a high risk of further transmission TRANS, co- infection MESHD or superinfection MESHD. Such highly infectious virus must be isolated and tested in highly sterilized laboratory. Further strict international laws and policies are required to stop the possible spread of experimental viruses, biological warfare and bioterrorism.

    Tocilizumab for treatment of mechanically ventilated patients with COVID-19

    Authors: Emily C Somers; Gregory A Eschenauer; Jonathan P Troost; Jonathan L Golob; Tejal N Gandhi; Lu Wang; Nina Zhou; Lindsay A Petty; Ji Hoon Baang; Nicholas O Dillman; David Frame; Kevin S Gregg; Dan R Kaul; Jerod Nagel; Twisha S Patel; Shiwei Zhou; Adam S Lauring; David A Hanauer; Emily Toth Martin; Pratima Sharma; Christopher M Fung; Jason M Pogue

    doi:10.1101/2020.05.29.20117358 Date: 2020-06-03 Source: medRxiv

    Background Severe COVID-19 can manifest in rapid decompensation and respiratory failure HP with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome MESHD in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. Methods We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections MESHD. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). Findings 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease MESHD (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death MESHD [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections MESHD (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection MESHD [22% vs. 15%; p=0.42]. Interpretation In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death MESHD despite higher superinfection MESHD occurrence. Randomized controlled trials are urgently needed to confirm these findings.

    Transcriptional profiling of immune and inflammatory responses in the context of SARS-CoV-2 fungal superinfection MESHD in a human airway epithelial model

    Authors: Claire Nicolas de Lamballerie; Andres Pizzorno; Julien Fouret; Lea szpiro; Blandine Padey; Julia Dubois; Thomas Julien; Aurelien Traversier; Victoria Duliere; Pauline Brun; Bruno Lina; Manuel Rosa-Calatrava; Olivier Terrier

    doi:10.1101/2020.05.19.103630 Date: 2020-05-19 Source: bioRxiv

    Superinfections MESHD of bacterial/fungal origin are known to affect the course and severity of respiratory viral infections MESHD. An increasing number of evidence indicate a relatively high prevalence SERO of superinfections MESHD associated with COVID-19, including invasive aspergillosis MESHD, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection MESHD we sought to determine and compare the host transcriptional response to SARS-CoV-2 versus Aspergillus superinfection MESHD, using a model of reconstituted humain airway epithelium. Our analyses reveal that both simple infection MESHD and superinfection MESHD induce a strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection MESHD in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection MESHD, such as an imbalanced type I/type III IFN, and an induction of several monocyte- and neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and but also management of severe forms of aspergillosis MESHD in this specific context.

    SARS-CoV-2 Origins and Evolution: Insights from Coronaviruses Recombination and Phylogenetic Analysis

    Authors: Alltalents Tutsirayi Murahwa; Harris Onywera; Fredrick Nindo

    doi:10.21203/ Date: 2020-05-19 Source: ResearchSquare

    Background: It is imperative in the midst of a global epidemic to investigate the origins of the infectious agent especially when it has reached parts of the world with either ailing economies or pre-existing political turmoil consistent with non-functional health systems. Methods: To explore the possibility of cross species infection MESHD, genomic recombination and the emergence of novel coronaviruses in the near future we carried out recombination and phylogenetic analysis to determine the spatio-temporal evolution and origins of the current SARS-CoV-2 virus. Results: Our findings prove using two robust recombination tools, RDPv4.100 and SimPlot3.5.1 analysis that SARS-CoV-2 is a recombinant of pangolin and bat RaTG13 sequences as been previously shown elsewhere. We also report one novel recombination event between two SARS-CoV-2 sequences (SARS-CoV-2 sequence, MT188341, SARS-CoV-2 sequence, MT293183). Bearing in mind that the prerequisite for recombination is the occurrence two viral sequences in the same reservoir, biological niche or host at the same time we postulate either co- infection MESHD with the two viral sequences, or superinfection MESHD, both scenarios have not been reported elsewhere. Conclusion: The possibility of recombination between the SARS-CoV-2 sequences poses the likelihood of the emergence of new and maybe more or less virulent “strains” of the virus. We believe that the future of science lies in our ability to be able to use computational based methods to predict the genetic sequences of infectious agents of the next epidemics. The addition of more SARS-CoV-2 sequences has a bearing on the understanding of the origin, evolution and clinical outcome prediction of given viral genomes. More SARS-CoV-2 sequences are needed to elucidate our understanding of this family of viruses.

    Characterization of SARS-CoV-2 viral diversity within and across hosts

    Authors: Palash Sashittal; Yunan Luo; Jian Peng; Mohammed El-Kebir

    doi:10.1101/2020.05.07.083410 Date: 2020-05-13 Source: bioRxiv

    In light of the current COVID-19 pandemic, there is an urgent need to accurately infer the evolutionary and transmission TRANS history of the virus to inform real-time outbreak management, public health policies and mitigation strategies. Current phylogenetic and phylodynamic approaches typically use consensus sequences, essentially assuming the presence of a single viral strain per host. Here, we analyze 621 bulk RNA sequencing samples and 7,540 consensus sequences from COVID-19 patients, and identify multiple strains of the virus, SARS-CoV-2, in four major clades that are prevalent within and across hosts. In particular, we find evidence for (i) within-host diversity across phylogenetic clades, (ii) putative cases of recombination, multi-strain and/or superinfections MESHD as well as (iii) distinct strain profiles across geographical locations and time. Our findings and algorithms will facilitate more detailed evolutionary analyses and contact tracing TRANS that specifically account for within-host viral diversity in the ongoing COVID-19 pandemic as well as future pandemics.

    Profiling COVID-19 pneumonia MESHD pneumonia HP progressing into the cytokine storm syndrome MESHD: results from a single Italian Centre study on tocilizumab versus standard of care.

    Authors: Luca Quartuccio; Arianna Sonaglia; Dennis McGonagle; Martina Fabris; Maddalena Peghin; Davide Pecori; Amato De Monte; Tiziana Bove; Francesco Curcio; Flavio Bassi; Salvatore De Vita; Carlo Tascini

    doi:10.1101/2020.05.01.20078360 Date: 2020-05-05 Source: medRxiv

    Abstract [250 words] Objective Approximately 5% of patients with coronavirus disease MESHD 2019 (COVID-19) develop a life-threatening pneumonia MESHD pneumonia HP that often occurs in the setting of increased inflammation MESHD or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. Methods Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia MESHD pneumonia HP were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). Results In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths MESHD (17.8+/-10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection MESHD. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection MESHD. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p<0.0001 for both) and higher neutrophils and lower lymphocyte levels (p= 0.04 and p=0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Conclusion Higher inflammatory markers, more infections MESHD and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.

    Clinical presentation and evolution of COVID-19 in immunosuppressed patients. Preliminary evaluation in a North Italian cohort on calcineurin-inhibitors based therapy

    Authors: Lorenzo Cavagna; Raffaele Bruno; Giovanni Zanframundo; Marilena Gregorini; Elena Seminari; Angela Di Matteo; Teresa Rampino; Carlomaurizio Montecucco; Stefano Pelenghi; Barbara Cattadori; Eleonora Francesca Pattoneri; Patrizio Vitulo; Alessandro Bertani; Gianluca Sambataro; Carlo Vancheri; Valentina Bonetto; Maria Cristina Monti; Elena Ticozzelli; Annalisa Turco; Tiberio Oggionni; Angelo Corsico; Veronica Codullo; Monica Morosini; Massimiliano Gnecchi; Carlo Pellegrini; Federica Meloni

    doi:10.1101/2020.04.26.20080663 Date: 2020-05-01 Source: medRxiv

    The clinical course of COVID-19 in patients undergoing chronic immunosuppressive therapy is yet poorly known. We performed a monocentric cross-sectional study describing the clinical course of COVID-19 in a cohort of patients from northern Italy treated with calcineurin-inhibitors for organ transplantation or rheumatic diseases MESHD. Data were collected by phone call and clinical chart review between March 27th- 31st 2020. COVID-19 related symptoms, rynopharingeal swab, therapeutic changes and outcome were assessed in 384 consecutive patients (57% males TRANS; median age TRANS 61 years, IQR 48-69). 331 patients (86%) received solid organ transplantation (kidney n=140, 36%, heart n=100, 26%, lung n=91, 24%) and 53 (14%) had a rheumatic disease MESHD. Calcineurin inhibitors were the only immunosuppressant administered in 46 patients (12%). 14 patients developed a confirmed COVID-19 (swab positivity) and 14 a clinical COVID-19 (only typical symptoms). Fever MESHD Fever HP (75%) and diarrhoea (50%) were the most common symptoms. Fourteen patients were hospitalized and 11 have already been dismissed. No patient required start/changes of the O2 therapy or developed superinfection MESHD. Only one patient, with metastatic lung cancer, died. In conclusion, COVID-19 showed a mild course in our cohort, with low mortality. Calcineurin inhibitor-based immunosuppressive regimens appear safe in this context and should not be discontinued.

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MeSH Disease
Human Phenotype

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