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    The case series of 34 patients with COVID-19 diagnosed with HIV infection MESHD from Central and Eastern European Countries - Euroguidelines in Central and Eastern Europe Network Group data

    Authors: Kerstin Kase; Agata Skrzat-Klapaczynska; Anne Vassilenko; Arjan Harxhi; Botond Lakatos; Gordana Dragovic Lukic; David Jilich; Antonija Verhaz; Nina Yancheva; Florentina Dumitrescu; Raimonda Matulionyte; Andrzej Horban; Justyna Dominika Kowalska; Michela Sali; Massimiliano Papi; Jayashree Kalpathy-Cramer; Fredrik Nyberg; Jose D Posada; Martina Recalde; Elena Roel; Karishma Shah; Nigam Shah; Lisa M Schilling; Vignesh Subbian; David Vizcaya; Lin Zhang; Ying Zhang; Hong Zhu; Li Liu; Peter Rijnbeek; George Hripcsak; Jennifer C.E Lane; Edward Burn; Christian Reich; Marc A Suchard; Talita Duarte-Salles; Krisitn Kosta; Patrick B Ryan; DANIEL PRIETO-ALHAMBRA; Christoph Lange; Georg Laue; Clemes Lier; Matthias Lindner; Georgios Marinos; Robert Markewitz; Jacob Nattermann; Rainer Noth; Peter Pickkers; Klaus F. Rabe; Alina Renz; Christoph Roecken; Jan Rupp; Annika Schaffarzyk; Alexander Scheffold; Jonas Schulte-Schrepping; Domagoj Schunck; Dirk Skowasch; Thomas Ulas; Klaus-Peter Wandinger; Michael Wittig; Johannes Zimmermann; Hauke Busch; Bimba F. Hoyer; Christoph Kaleta; Jan Heyckendorf; Matthijs Kox; Jan Rybniker; Stefan Schreiber; Joachim Schultze; Philip Rosenstiel; - HCA Lung Biological Network; - Deutsche COVID-19 Omics Initiative (DeCOI)

    doi:10.1101/2020.09.16.20191528 Date: 2020-09-18 Source: medRxiv

    Background: A novel coronavirus (SARS-CoV-2) causing coronavirus disease MESHD (COVID-19) was detected at the end of 2019 in China. There are many COVID-19 studies in progress however, little is known about the course of COVID-19 in people living with HIV MESHD (PLWH). The aim of our study was to describe epidemiology and clinical characteristics of PLWH diagnosed with COVID-19 reported form Central and Eastern European Countries. Methods: On-line survey was sent to Euroguidelines in Central and Eastern Europe (ECEE) Network Group. Analysis included all confirmed COVID-19 cases between March 11 and June 26 2020 among PLWH in 12 countries: Albania, Belarus, Bosnia and Herzegovina, Bulgaria, Czech Republic, Estonia, Hungary, Lithuania, Poland , Romania, Russia MESHD, and Serbia. Results: In total 34 cases were reported. The mean age TRANS of those patients was 42.7 years (IQR=35.8-48.5) and most of the patients were male TRANS (70.6% vs 29.4%). The mean CD4+ T-cell count prior COVID-19 diagnosis was 558 cells/mm3 (IQR=312-719) and HIV MESHD RNA viral load (VL) was undetectable in 18 of 34 (53%) cases, the data about most recent HIV RNA VL was not available in three cases (8,8%). Comorbidities were observed in 19 (55.9%) patients, mostly cardiovascular disease MESHD (27,8%), and in 10 (29.4%) patients had coinfection, mostly chronic hepatitis HP chronic hepatitis MESHD C (87.5%). The clinical course of COVID-19 was asymptomatic TRANS in 4 (12%) cases, mild disease without hospitalization was reported in 11 (32%) cases. Stable patients with respiratory and/or systemic symptoms have been documented in 14 (41%) cases; 5 (15%) patients were clinically unstable with respiratory failure HP respiratory failure MESHD. Full recovery was reported in 31 (91%) cases, two patients died. In one case the data was not available. Conclusion: This study from 12 countries in Central and Eastern Europe region indicates no alarming signals of increased morbidity or mortality from COVID-19 among HIV-positive persons there is a need for further research.

    COVID-19 Pandemic and the South African Podiatrist

    Authors: Bernhard Zipfel; Nadia Dembskey

    id:10.20944/preprints202009.0425.v1 Date: 2020-09-18 Source: Preprints.org

    The Coronavirus disease MESHD 2019 (COVID-19) pandemic is clearly taking a firmer grip on South Africa and more podiatrists will face the potential transmission TRANS of SARS-CoV-2. Government response was swift with the implementation of a travel TRANS ban, strict national lockdown as well as social distancing and hygiene protocols in line with international health regulations. Co-morbidities such as tuberculosis MESHD and HIV MESHD/ AIDS MESHD, endemic to South Africa, are considered a dangerous combination with COVID-19, making many South Africans vulnerable to contracting the COVID-19. Patients with diabetes MESHD as well as the aged TRANS are vulnerable, both in terms of potential combined complications and challenges in continuity in foot care. The demands of the pandemic may outstrip the ability of the health systems to cope. Should this time arrive, all healthcare practitioners, including podiatrists, would have to step in and take on a role beyond their scope of practice in order to ensure that the healthcare system does not get overwhelmed. It is important for podiatrists to keep abreast with the developments around the COVID-19, in order that they may institute appropriate clinical practice which will ensure maximum protection for themselves, staff and patients as well as providing quality foot health care.

    SARS-CoV-2 ribosomal frameshifting pseudoknot: Improved secondary structure prediction and detection of inter-viral structural similarity

    Authors: Luke Trinity; Lance Lansing; Hosna Jabbari; Ulrike Stege; Pierre T Felix Sr.; B S Karothia; K T Chelvam; Sandeep Singh; Abhay Gupta; Ram Govind Yadav; Ruchi Yadav; Greshma T S; Pramod Kushwah; Ravi Bhushan; D P Nagar; Manvendra Nandan; Subodh Kumar; Duraipandian Thavaselvam; Devendra Kumar Dubey; Paul Lin; Hila Shaim; Sean G Yates; David Marin; Indreshpal Kaur; Sheetal Rao; Duncan Mak; Angelique Lin; Qi Miao; Jinzhuang Dou; Ken Chen; Richard Champlin; Elizabeth J Shpall; Katayoun Rezvani

    doi:10.1101/2020.09.15.298604 Date: 2020-09-15 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has led to the COVID-19 pandemic; a pandemic of a scale that has not been seen in the modern era. Despite over 29 million reported cases and over 900,000 deaths worldwide as of September 2020, herd immunity and widespread vaccination efforts by many experts are expected to be insufficient MESHD in addressing this crisis for the foreseeable future. Thus, there is an urgent need for treatments that can lessen the effects of SARS-CoV-2 in patients who become seriously affected. Many viruses including HIV MESHD, the common cold, SARS-CoV and SARS-CoV-2 MESHD use a unique mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to successfully replicate and infect cells in the human host. SARS-CoV MESHD (the coronavirus responsible for SARS) and SARS-CoV-2 possess a unique RNA structure, a three-stemmed pseudoknot, that stimulates -1 PRF. Recent experiments identified that small molecules can be introduced as antiviral agents to bind with the pseudoknot and disrupt its stimulation of -1 PRF. If successfully developed, small molecule therapy that targets -1 PRF in SARS-CoV-2 is an excellent strategy to improve patients' prognoses. Crucial to developing these successful therapies is modeling the structure of the SARS-CoV-2 -1 PRF pseudoknot. Following a structural alignment approach, we identify similarities in the -1 PRF pseudoknots of the novel coronavirus SARS-CoV-2, the original SARS-CoV MESHD, as well as a third coronavirus: MERS MESHD-CoV, the coronavirus responsible for Middle East Respiratory Syndrome MESHD ( MERS MESHD). In addition, we provide a better understanding of the SARS-CoV-2 -1 PRF pseudoknot by comprehensively investigating the structural landscape using a hierarchical folding approach. Since understanding the impact of mutations is vital to long-term success of treatments that are based on predicted RNA functional structures, we provide insight on SARS-CoV-2 -1 PRF pseudoknot sequence mutations and their effect on the resulting structure and its function.

    Molecular basis for SARS-CoV-2 spike affinity for human ACE2 receptor

    Authors: Julian M. Delgado; Nalvi Duro; David M. Rogers; Alexandre Tkatchenko; Sagar A. Pandit; Sameer Varma; Sarah K Hilton; John Huddleston; Rachel Eguia; Katharine HD Crawford; Adam S Dingens; Rachel S Nargi; Rachel E Sutton; Naveenchandra Suryadevara; Paul W Rothlauf; Zhuoming Liu; Sean PJ Whelan; Robert H Carnahan; James E Crowe Jr.; Jesse D Bloom; Miles P Davenport; Stephen J Kent

    doi:10.1101/2020.09.10.291757 Date: 2020-09-10 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) has caused substantially more infections MESHD, deaths, and economic disruptions than the 2002-2003 SARS-CoV MESHD. The key to understanding SARS-CoV-2's higher infectivity may lie in its host receptor recognition mechanism. This is because experiments show that the human ACE2 protein, which serves as the primary receptor for both CoVs, binds to CoV-2's spike protein 5-20 fold stronger than SARS-CoV's spike MESHD protein. The molecular basis for this difference in binding affinity, however, remains unexplained and, in fact, a comparison of X-ray structures leads to an opposite proposition. To gain insight, we use all-atom molecular dynamics simulations. Free energy calculations indicate that CoV-2's higher affinity is due primarily to differences in specific spike residues that are local to the spike-ACE2 interface, although there are allosteric effects in binding. Comparative analysis of equilibrium simulations reveals that while both CoV and CoV-2 spike-ACE2 complexes have similar interfacial topologies, CoV-2's spike protein engages in greater numbers, combinatorics and probabilities of hydrogen bonds and salt bridges with ACE2. We attribute CoV-2's higher affinity to these differences in polar contacts, and these findings also highlight the importance of thermal structural fluctuations in spike-ACE2 complexation. We anticipate that these findings will also inform the design of spike-ACE2 peptide blockers that, like in the cases of HIV MESHD and Influenza, can serve as antivirals.

    Performance SERO assessment of 11 commercial serological tests SERO for SARS-CoV-2 on hospitalized COVID-19 patients

    Authors: Claudia Serre-Miranda; Claudia Nobrega; Susana Roque; Joao Canto-Gomes; Carolina S Silva; Neide Vieira; Palmira Barreira-Silva; Pedro Alves-Peixoto; Jorge Cotter; Ana Reis; Mariana Formigo; Helena Sarmento; Olga Pires; Alexandre Carvalho; Dmitri Y Petrovykh; Lorena Dieguez; Joao C Sousa; Nuno Sousa; Carlos Capela; Joana A Palha; Pedro G Cunha; Margarida Correia-Neves

    doi:10.1101/2020.08.06.20168856 Date: 2020-08-07 Source: medRxiv

    Commercial availability of serological tests SERO to evaluate immunoglobulins (Ig) towards severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has grown exponentially since the onset of COVID-19 outbreak. Their thorough validation is of extreme importance before using them as epidemiological tools to infer population seroprevalence SERO, and as complementary diagnostic tools to molecular approaches (e.g. RT-qPCR). Here we assayed commercial serological tests SERO (semiquantitative and qualitative) from 11 suppliers in 126 samples collected from hospitalized COVID-19 patients, and from 36 healthy and HIV-infected MESHD individuals (collected at the pre-COVID-19 pandemic). Specificity was above 95% in 9 tests. Samples from COVID-19 patients were stratified by days since symptoms onset TRANS (<10, 10-15, 16-21 and >21 days). Tests sensitivity SERO increases with time since symptoms onset TRANS, and peaks at 16-21 days for IgM and IgA (maximum: 91.2%); and from 16-21 to >21 days for IgG, depending on the test (maximum: 94.1%). Data from semiquantitative tests show that patients with severe clinical presentation have lower relative levels of IgM, IgA and IgG at <10 days since symptoms onset TRANS in comparison to patients with non-severe presentation. At >21 days since symptoms onset TRANS the relative levels of IgM and IgG (in one test) are significantly higher in patients with severe clinical presentation, suggesting a delay in the upsurge of Ig against SARS-CoV-2 in those patients. This study highlights the high specificity of most of the evaluated tests, and sensitivity SERO heterogeneity. Considering the virus genetic evolution and population immune response to it, continuous monitoring of commercially available serological tests SERO towards SARS-CoV-2 is necessary.

    The Diagnostic Trap Occurred in Two COVID-19 Cases Combined Pneumocystis Pneumonia MESHD Pneumonia HP in Patient with AIDS MESHD

    Authors: Wei Guo; Maomao Wang; Fangzhao Ming; Weiming Tang; Ke Liang

    doi:10.21203/rs.3.rs-53350/v1 Date: 2020-08-04 Source: ResearchSquare

    Background : The limited knowledge on the diagnosis of Coronavirus disease MESHD 2019 (COVID-19) at the early stage of the pandemic may lead to misdiagnoses, especially when the nucleic acid inspection cannot meet the mass requirement. This condition is even actual for people who are living with HIV MESHD/ AIDS MESHD (PLWHA), for the latter is vulnerable to variable infections. Case Presentation : In this short communication, we introduced two HIV infected MESHD individuals who had PCP but was misdiagnosed as COVID-19 initially, and finally infected with SARS-CoV-2 in hospital in Wuhan, China. Eventually, both patients improved soon after they were switched to the treatment of SMZ/TMP.Conclusions : We suggested that the hospitalized COVID-19 cases should be screened with HIV MESHD and other pathogens, to prevent that PLWHA who have PCP from being misdiagnosed as COVID-19.

    Acute transverse myelitis MESHD myelitis HP in a HIV MESHD-positive patient with COVID-19

    Authors: Vitalie Lisnic; Victor Nemtan; Evghenia Hacina; Galina Topciu; Elena Manole; Majda M. Thurnher; Rüdiger von Kummer

    doi:10.21203/rs.3.rs-50901/v1 Date: 2020-07-29 Source: ResearchSquare

    Immunocompromised status keeps on being a challenge for a neurologist, especially in the context of the coronavirus disease MESHD – 19 (COVID-19) pandemic. We report a clinical case of a human-immunodeficiency virus MESHD immunodeficiency HP virus ( HIV MESHD) - positive patient who developed an acute transverse myelitis MESHD myelitis HP. Magnetic Resonance Imaging (MRI) examination showed longitudinally extensive spinal cord abnormality MESHD spinal cord abnormality HP, and laboratory tests confirmed SARS-CoV-2 infection MESHD. The patient responded to methylprednisolone pulse therapy and therapeutic plasma SERO exchange. No cases of HIV-positive MESHD patients with myelitis HP myelitis MESHD and COVID-19 has been reported yet.

    Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2’s main protease

    Authors: mohamed mahdi; János András Mótyán; Zsófia Ilona Szojka; Mária Golda; Márió Miczi; József Tőzsér

    doi:10.21203/rs.3.rs-40776/v1 Date: 2020-07-09 Source: ResearchSquare

    Background The pandemic caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has resulted in millions of infections worldwide. While the search for an effective antiviral is still ongoing, experimental therapies based on repurposing of available antivirals is being attempted, of which HIV protease inhibitors (PIs) have gained considerable interest. Inhibition profiling of the PIs directly against the viral protease has never been attempted in vitro, and while few studies reported an efficacy of lopinavir and ritonavir in SARS-CoV-2 context, the mechanism of action of the drugs remains to be validated.Methods We carried out an in-depth analysis of the efficacy of HIV PIs against the main protease of SARS-CoV-2 (Mpro) in cell culture and in vitro enzymatic assays, using a methodology that enabled us to focus solely on any potential inhibitory effects of the inhibitors against the viral protease.Results Lopinavir, ritonavir, darunavir, saquinavir, and atazanavir were able to inhibit the viral protease in cell culture, albeit in concentrations much higher than their achievable plasma SERO levels, given their current drug formulations. While inhibition by lopinavir was attributed to its cytotoxicity MESHD, ritonavir was the most effective of the panel, with IC50 of 13.7 µM. Atazanavir on the other hand was the only PI to inhibit the viral protease both in cell culture and in our in vitro enzymatic assay.Conclusion Targeting of SARS-CoV-2 Mpro by some of the HIV MESHD PIs might be of limited clinical potential, given the high concentration of the drugs required to achieve significant inhibition. Therefore, given their weak inhibition of the viral protease, any potential beneficial effect of the PIs in COVID-19 context might perhaps be attributed to acting on other molecular target(s), rather than SARS-CoV-2 Mpro.

    Anti- SARS-CoV-2 main protease complex (Mpro) activity of Palmatine


    doi:10.21203/rs.3.rs-38145/v1 Date: 2020-06-27 Source: ResearchSquare

    The Pandemic situation caused due to SARS-CoV-2 causing Coronavirus Disease MESHD (CoVID-19) around globe. Recent, COVID-19 main protease complex (Mpro), highly modulating enzyme in SARS-CoV-2 was reported for viral replication and transcription. This multifunctionality of Mpro attracts for identification of potential drug target. Considering impact, In silico analysis was performed for Palmatine alkaloid against Mpro. Naturally, present in Tinospora cordifolia, found effective against Cancer MESHD, HIV MESHD, viral infections MESHD, diabetics MESHD. In methods, physico-chemical analysis by ProtParam tool and Structure of Mpro was predicted by SWISS-MODEL Workspace homology modeling server. Superimposition Structure and significant equal QMQE, QSQE values were found for eight highly similar templates. Structural assessment validation by Ramachandran plot (97.67% favoured), Local Quality estimate ratio (>0.6) and higher QMEAN score (y-axis). Further, docking was performed with validated Mpro model by SwissDock server. Interaction with -8.281919 ΔG indicates reliable Interaction. Also, comparative docking reveals, most favoured Palmatine interaction. Thus, an attempt was made to find potent inhibitor for SARS-CoV-2, as there is no promising and specific anti-viral drug or vaccine available for prevention and treatment of infections MESHD. However, In Vitro studies are required. Toxicity MESHD studies reported against Palmatine for acute effect (135 mg/kg body weight) on mouse model LD 50.

    Non-coronavirus Genome Sequences Identified from Metagenomic Analysis of Clinical Samples from COVID-19 Infected Patients: An Evidence for Co-infection MESHD

    Authors: Mohamed Abouelkhair

    id:10.20944/preprints202005.0505.v2 Date: 2020-06-18 Source: Preprints.org

    In December 2019, pneumonia HP pneumonia MESHD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease MESHD: coronavirus disease MESHD 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection MESHD is a critical determinant of both viral fitness and infection MESHD outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected MESHD patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus MESHD immunodeficiency HP virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis HP hepatitis MESHD virus (1/68) genome sequences were detected in SARS-CoV-2 infected MESHD patients.

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