Corpus overview


MeSH Disease

COVID-19 (501)

Fever (105)

Pneumonia (98)

Death (81)

Hypertension (73)

HGNC Genes

SARS-CoV-2 proteins

ProteinN (8)

ProteinS (4)

ORF1ab (1)

ProteinS1 (1)


SARS-CoV-2 Proteins
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    SARS-CoV-2 infection MESHD induces autoimmune antibody secretion more in lean than in obese MESHD COVID-19 MESHD patients

    Authors: Daniela Frasca; Lisa Reidy; Maria Romero; Alain Diaz; Carolyn Cray; Kristin Kahl; Bonnie Blomberg

    doi:10.1101/2021.05.05.21256686 Date: 2021-05-11 Source: medRxiv

    Background/Objectives: Obesity decreases the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 MESHD patients. How obesity impacts MESHD the secretion of autoimmune antibodies in COVID-19 MESHD patients, however, is not understood. The serum of adult COVID-19 MESHD patients contains autoimmune antibodies generated in response to virus-induced tissue damage and cell death leading to the release of intracellular antigens not known to be immunogenic autoantigens. The objective of this study is to evaluate the presence of autoimmune antibodies in COVID-19 MESHD patients with obesity MESHD. Subjects/Methods: Thirty serum samples from individuals who tested positive for SARS-CoV-2 infection MESHD by RT-PCR were collected from inpatient and outpatient settings. Of these, 15 were lean (BMI<25), and 15 were obese MESHD (BMI [≥]30). Control serum samples were from 30 uninfected individuals, age- gender- and BMI-matched, recruited before the current pandemic. Serum IgG antibodies against two autoimmune specificities, as well as against SARS-CoV-2 Spike PROTEIN protein, were measured by ELISA. IgG autoimmune antibodies were specific for malondialdehyde (MDA), a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens ( AD MESHD), markers of virus-induced cell death in the obese AT MESHD. Results: Our results show that SARS-CoV-2 infection MESHD induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese MESHD patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese MESHD versus lean COVID-19 MESHD patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 MESHD patients have been correlated with serum levels of C-reactive protein HGNC ( CRP HGNC), a general marker of inflammation MESHD, we also evaluated the association of anti-MDA and anti-AT antibodies with serum CRP HGNC and found a significant association between CRP HGNC and autoimmune antibodies in our cohort of lean and obese MESHD COVID-19 MESHD patients. Conclusions: Our results highlight the importance of evaluating the quality of the antibody response in COVID-19 MESHD patients with obesity MESHD, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population that is at higher risk of responding poorly to infection with SARS-CoV-2 compared to lean controls.

    Identifying risk factors for COVID-19 MESHD severity and mortality in the UK Biobank MESHD

    Authors: Iqbal Madakkatel; Catherine King; Ang Zhou; Anwar Mulugeta; Amanda Lumsden; Mark McDonnell; Elina Hypponen

    doi:10.1101/2021.05.10.21256935 Date: 2021-05-11 Source: medRxiv

    Severe acute respiratory syndrome coronavirus has infected over 114 million people worldwide as of March 2021, with worldwide mortality rates ranging between 1-10%. We use information on up to 421,111 UK Biobank participants to identify possible predictors for long-term susceptibility to severe COVID-19 infection MESHD (N =1,088) and mortality (N =376). We include 36,168 predictors in our analyses and use a gradient boosting decision tree (GBDT) algorithm and feature attribution based on Shapley values, together with traditional epidemiological approaches to identify possible risk factors. Our analyses show associations between socio-demographic factors (e.g. age, sex, ethnicity, education, material deprivation, accommodation type) and lifestyle indicators (e.g. smoking, physical activity, walking pace, tea intake, and dietary changes) with risk of developing severe COVID-19 MESHD symptoms. Blood ( cystatin C HGNC, C-reactive protein HGNC, gamma glutamyl transferase and alkaline phosphatase) and urine (microalbuminuria) biomarkers measured more than 10 years earlier predicted severe COVID-19 MESHD. We also confirm increased risks for several pre-existing disease outcomes (e.g. lung diseases MESHD, type 2 diabetes MESHD, hypertension MESHD, circulatory diseases, anemia MESHD, and mental disorders MESHD). Analyses on mortality were possible within a sub-group testing positive for COVID-19 MESHD infection (N =1,953) with our analyses confirming association between age, smoking status, and prior primary diagnosis of urinary tract infection MESHD.

    COVID-19 MESHD cases from the first local outbreak of SARS-CoV-2 B.1.1.7 variant in China presented more serious clinical features: a prospective, comparative cohort study

    Authors: Yang Song M.D.; Ziruo Ge M.D.; Shuping Cui M.Sc.; Di Tian M.D.; Gang Wan M.D.; Shuangli Zhu B.Sc.; Xianbo Wang M.D.; Yu Wang M.D.; Xiang Zhao M.D.; Pan Xiang M.D.; Yanli Xu M.D.; Tingyu Zhang M.D.; Long Liu M.D.; Gang Liu M.D.; Yanhai Wang M.Sc.; Jianbo Tan M.D.; Wei Zhang M.D.; Wenbo Xu M.D.; Zhihai Chen M.D.

    doi:10.1101/2021.05.04.21256655 Date: 2021-05-08 Source: medRxiv

    Background: The SARS-CoV-2 B.1.1.7 variant which was first identified in the United Kingdom (U.K.) has increased sharply in numbers worldwide and was reported to be more contagious. On January 17, 2021, a COVID-19 MESHD clustered outbreak caused by B.1.1.7 variant occurred in a community in Daxing District, Beijing, China. Three weeks prior, another non-variant (lineage B.1.470) COVID-19 MESHD outbreak occurred in Shunyi District, Beijing. This study aimed to investigate the clinical features of B.1.1.7 variant infection. Methods: A prospective cohort study was conducted on COVID-19 MESHD cases admitted to Ditan hospital since January 2020. Data of 74 COVID-19 MESHD cases from two independent COVID-19 MESHD outbreaks in Beijing were extracted as study subjects from a Cloud Database established in Ditan hospital, which included 41 Shunyi cases (Shunyi B.1.470 group) and 33 Daxing cases (Daxing B.1.1.7 group) that have been hospitalized since December 25, 2020 and January 17, 2021, respectively. We conducted a comparison of the clinical characteristics, RT-qPCR results and genomic features between the two groups. Findings: Cases from Daxing B.1.1.7 group (15 [45.5%] male; median age, 39 years [range, 30.5, 62.5]) and cases from Shunyi B.1.470 group (25 [61.0%] male; median age, 31 years [range, 27.5, 41.0]) had a statistically significant difference in median age (P =0.014). Seven clinical indicators of Daxing B.1.1.7 group were significantly higher than Shunyi B.1.470 group including patients having fever MESHD over 38 (14/33 [46.43%] in Daxing B.1.1.7 group vs. 9/41 (21.95%) in Shunyi B.1.470 group [P = 0 .015]), C-reactive protein HGNC ([CRP, mg/L], 4.30 [2.45, 12.1] vs. 1.80, [0.85, 4.95], [P = 0.005]), Serum amyloid A ([SAA, mg/L], 21.50 [12.50, 50.70] vs. 12.00 [5.20, 26.95], [P = 0.003]), Creatine Kinase ([CK, U/L]), 110.50 [53.15,152.40] vs. 70.40 [54.35,103.05], [P = 0.040]), D-dimer ([DD, mg/L], 0.31 [0.20, 0.48] vs. 0.24 [0.17,0.31], [P = 0.038]), CD4+ T lymphocyte ([CD4+ T, mg/L], [P = 0.003]) , and Ground-glass opacity (GGO) in lung (15/33 [45.45%] vs. 5/41 [12.20%], [P =0.001]). After adjusting for the age factor, B.1.1.7 variant infection was the risk factor for CRP (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), SAA (0.011, 5.031, [1.459, 17.354]), CK (0.034, 4.34, [0.05, 0.91]), CD4+ T ( 0.029, 3.31, [1.13, 9.71]), and GGO (0.005, 5.418, [1.656, 17.729]) of patients. The median Ct value of RT-qPCR tests of the N-gene PROTEIN target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). The phylogenetic analysis showed that only 2 amino acid mutations in spike protein PROTEIN were detected in B.1.470 strains while B.1.1.7 strains had 3 deletions and 7 mutations. Interpretation: Clinical features including a more serious inflammatory response, pneumonia MESHD and a possible higher viral load were detected in the cases infected with B.1.1.7 SARS-CoV-2 variant. It could therefore be inferred that the B.1.1.7 variant may have increased pathogenicity.


    Authors: Zelalem Temesgen; Charles D. Burger; Jason Baker; Christopher Polk; Claudia Libertin; Colleen Kelley; Vincent C Marconi; Robert Orenstein; Cameron Durrant; Dale Chappell; Omar Ahmed; Gabrielle Chappell; Andrew Badley

    doi:10.1101/2021.05.01.21256470 Date: 2021-05-05 Source: medRxiv

    BACKGROUND: Severe COVID19 MESHD pneumonia MESHD results from a hyperinflammatory immune response (cytokine storm, CS), characterized by GM CSF HGNC mediated activation and trafficking of myeloid cells, leading to elevation of downstream inflammatory chemokines ( MCP1 HGNC, IL8 HGNC, IP10 HGNC), cytokines ( IL6 HGNC, IL1 HGNC), and other markers of systemic inflammation MESHD ( CRP HGNC, D dimer, ferritin). CS leads to fever MESHD, hypotension MESHD, coagulopathy MESHD, respiratory failure MESHD, ARDS, and death MESHD. Lenzilumab is a novel Humaneered anti-human GM CSF HGNC monoclonal antibody that directly binds GM CSF HGNC and prevents signaling through its receptor. The LIVE AIR Phase 3 randomized, double blind, placebo controlled trial investigated the efficacy and safety of lenzilumab to assess the potential for lenzilumab to improve the likelihood of ventilator free survival (referred to herein as survival without ventilation, SWOV), beyond standard supportive care, in hospitalized subjects with severe COVID-19 MESHD. METHODS: Subjects with COVID-19 MESHD (n=520), >18 years <94% oxygen saturation on room air and/or requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized to receive lenzilumab (600 mg, n=261) or placebo (n=259) via three intravenous infusions administered 8 hours apart. Subjects were followed through Day 28 following treatment. RESULTS: Baseline demographics were comparable between the two treatment groups: male, 64.7%; mean age, 60.5 years; mean BMI, 32.5 kg/m2; mean CRP HGNC, 98.36 mg/L; CRP HGNC was <150 mg/L in 77.9% of subjects. The most common comorbidities were obesity MESHD (55.1%), diabetes MESHD (53.4%), chronic kidney disease MESHD (14.0%), and coronary artery disease MESHD (13.6%). Subjects received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the likelihood of SWOV by 54% in the mITT population (HR: 1.54; 95% CI: 1.02 to 2.31, p=0.041) and by 90% in the ITT population (HR: 1.90; 1.02 to 3.52, nominal p=0.043) compared to placebo. SWOV also relatively improved by 92% in subjects who received both corticosteroids and remdesivir (1.92; 1.20 to 3.07, nominal p=0.0067); by 2.96-fold in subjects with CRP HGNC<150 mg/L and age <85 years (2.96; 1.63 to 5.37, nominal p=0.0003); and by 88% in subjects hospitalized <2 days prior to randomization (1.88; 1.13 to 3.12, nominal p=0.015). Survival was improved by 2.17-fold in subjects with CRP HGNC<150 mg/L and age <85 years (2.17; 1.04 to 4.54, nominal p=0.040). CONCLUSION: Lenzilumab significantly improved SWOV in hospitalized, hypoxic subjects with COVID-19 MESHD pneumonia MESHD over and above treatment with remdesivir and/or corticosteroids. Subjects with CRP HGNC<150 mg/L and age <85 years demonstrated an improvement in survival and had the greatest benefit from lenzilumab. NCT04351152

    Evidence for the utility of cfDNA plasma concentrations to predict disease severity in COVID-19 MESHD

    Authors: Katharina Hoeter; Elmo Neuberger; Susanne Fischer; Manuel Herbst; Ema Juskeviciute; Heidi Rossmann; Martin F Sprinzl; Perikles Simon; Marc Bodenstein; Michael K.E. Schäfer

    doi:10.1101/2021.04.29.21256291 Date: 2021-05-02 Source: medRxiv

    COVID-19 MESHD is a pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19 MESHD. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various disease conditions. The aim of this retrospective and observational pilot study was to examine the potential value of cfDNA plasma concentrations as a correlative biomarker in hospitalized COVID-19 MESHD patients. Lithium-Heparin plasma samples were obtained from twenty-one COVID-19 MESHD patients during hospitalization in the University Medical Center of Mainz, Germany, and the cfDNA concentrations were determined by quantitative PCR yielding amplicons of long interspersed nuclear elements (LINE-1). cfDNA plasma concentrations of COVID-19 MESHD patients ranged between 247.5 and 6346.25 ng/ml and the mean concentrations were 1831 {+/-} 1388 ng/ml ({+/-} standard deviation). Correlations were found between cfDNA levels and the occurrence of acute respiratory distress symptom (ARDS), acute kidney injury MESHD ( AKI MESHD), myositis MESHD, neurological complications MESHD, bacterial superinfection and disease severity as defined by sepsis-related organ failure assessment score (SOFA) score. D-Dimer and C-reactive-protein ( CRP HGNC), determined by clinical laboratory analysis, showed the highest correlations with cfDNA levels. The results of this observational study suggest that cfDNA plasma concentrations may serve as a predictive biomarker of disease severity in COVID-19 MESHD. Prospective studies enrolling larger patient cohorts are ongoing to test this hypothesis.

    COVID-19 MESHD and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes

    Authors: Agustin Ciapponi; Ariel Bardach; Daniel Comande; Mabel Berrueta; Fernando J Argento; Federico Rodriguez Cairoli; Natalia Zamora; Victoria Santa Maria; Xu Xiong; Sabra Zaraa; Agustina Mazzoni; Pierre Buekens

    doi:10.1101/2021.04.29.21256327 Date: 2021-05-02 Source: medRxiv

    Background We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 MESHD on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783). Methods We searched literature databases and COVID-19 MESHD research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 MESHD and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR's results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables. Results We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 MESHD clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein HGNC (28-96%), lymphopenia MESHD (34-80%), and pneumonia MESHD signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight MESHD (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 MESHD versus non- COVID-19 MESHD pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks. Conclusion This comprehensive overview supports that pregnant women with COVID-19 MESHD may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.

    A systematic review on Multisystem Inflammatory Syndrome in Children ( MIS HGNC-C) with COVID-19 MESHD: Development of a scoring system for clinical diagnosis

    Authors: Dr.Suchitra Vishwambhar Surve; Ms. Shaini Joseph; Dr. Rahul K Gajbhiye; Smita D Mahale; Dr. Deepak N Modi

    doi:10.1101/2021.04.23.21255879 Date: 2021-04-25 Source: medRxiv

    Background There is growing evidence of Multisystem Inflammatory Syndrome MESHD in Children ( MIS HGNC-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 MESHD presenting with or without MIS HGNC-C. Methods The individual patient data from 119 studies accounting for 333 children were analyzed. We devised a scoring system as per WHO criteria to classify the patients as MIS HGNC-C or without MIS HGNC-C. A score of 3 was given for the presence of fever MESHD (>24h) and a score of 1 for lab-confirmed diagnosis of SARS-CoV-2. Additionally, a score of 1 was given for a) rash MESHD or conjunctivitis MESHD or muco-cutaneous inflammation MESHD signs, b) hypotension MESHD or shock, c) diarrhea MESHD, vomiting MESHD or abdominal pain MESHD, d) features of myocardial dysfunction MESHD as determined by abnormal eco-cardiography or elevated Troponin or N-terminal pro b-type natriuretic peptide (NT-proBNP), e) evidence of coagulopathy MESHD as evidenced by elevated levels of prothrombin time PT, partial thromboplastin time PTT or D-dimer, f) laboratory evidence of inflammation MESHD as determined by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein HGNC ( CRP HGNC) or procalcitonin. A negative score of (-3) was given when there was a diagnosis of sepsis MESHD, staphylococcal or streptococcal shock syndrome MESHD. Based on these criteria, a minimum score of 6 was essential to classify the child as MIS HGNC-C. Results Based on this score, 18% (52/289) of cases were identified to be MIS HGNC-C. A greater proportion of children with MIS HGNC-C had cardiac involvement ( MIS HGNC-C 80% vs Non- MIS HGNC-C 20%) and gastrointestinal involvement MESHD ( MIS HGNC-C 71% vs Non- MIS HGNC-C 12%). Lymphopenia MESHD was commonly reported in MIS-C ( MIS HGNC-C 54.2% vs Non- MIS HGNC-C 29.7%). In addition to routine inflammatory markers, significamtly greater proportion of children with MIS-C had elevated Ferritin, LDH, Fibrinogen HGNC and IL-6 HGNC. Children with MIS HGNC-C were less likely to have respiratory symptoms like cough ( MIS HGNC-C 25% vs Non- MIS HGNC-C 75%) and rhinorrhea MESHD ( MIS HGNC-C 4% vs Non- MIS HGNC-C 22.8%). A greater proportion of children with MIS HGNC-C required intensive care and aggressive treatment; and mortality rates were also higher in MIS-C group ( MIS HGNC-C 10% vs Non- MIS HGNC-C 1%). Conclusion The children with COVID-19 MESHD having cardiac and/or gastrointestinal involvement MESHD are more likely to develop MIS HGNC-C. The children with MIS HGNC-C have higher mortality rates. The scoring system developed herein will aid clinicians in patient diagnosis and timely management.

    Gut microbiota diversity and C-Reactive Protein HGNC are predictors of disease severity in COVID-19 MESHD patients

    Authors: Andre Moreira-Rosario; Claudia Marques; Helder Pinheiro; Joao Ricardo Araujo; Pedro Ribeiro; Rita Rocha; Ines Mota; Diogo Pestana; Rita Ribeiro; Ana Pereira; Maria Jose de Sousa; Jose Pereira-Leal; Jose de Sousa; Juliana Morais; Diana Teixeira; Julio Cesar Rocha; Marta Silvestre; Nuno Principe; Nuno Gatta; Jose Amado; Lurdes Santos; Fernando Maltez; Ana Boquinhas; Germano de Sousa; Nuno Germano; Goncalo Sarmento; Cristina Granja; Pedro Povoa; Ana Faria; Conceicao Calhau

    doi:10.1101/2021.04.20.440658 Date: 2021-04-23 Source: bioRxiv

    Risk factors for COVID-19 MESHD disease severity are still poorly understood. Considering the pivotal role of gut microbiota on host immune and inflammatory functions, we investigated the association between changes in gut microbiota composition and the clinical severity of COVID-19 MESHD. We conducted a multicentre cross-sectional study prospectively enrolling 115 COVID-19 MESHD patients categorized according to: 1) WHO Clinical Progression Scale - mild 19 (16.5%), moderate 37 (32.2%) or severe 59 (51.3%); and 2) location of recovery from COVID-19 MESHD - ambulatory 14 (household isolation; 12.2%), hospitalized in ward 40 (34.8%) or intensive care unit 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing and data obtained was further related with clinical parameters of COVID-19 MESHD patients. Risk factors for COVID-19 MESHD severity were identified by univariate and multivariable logistic regression models. In comparison with mild COVID-19 MESHD patients, the gut microbiota of moderate and severe patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such as Roseburia and Lachnospira genera. Multivariable regression analysis showed that Shannon index diversity (odds ratio [OR] 2.85 [95% CI 1.09-7.41]; p=0.032) and C-Reactive Protein HGNC (OR 3.45 [95% CI 1.33-8.91]; p=0.011) were risk factors for COVID-19 MESHD severe disease (a score of 6 or higher in WHO clinical progression scale). In conclusion, our results demonstrated that hospitalised moderate and severe COVID-19 MESHD patients have microbial signatures of gut dysbiosis MESHD and for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker for COVID-19 MESHD disease severity.

    Mid-Regional pro-Adrenomedullin (MR-proADM), C-Reactive Protein HGNC ( CRP HGNC) and Other Biomarkers in the Early Identification of Disease Progression in COVID-19 MESHD Patients in the Acute NHS Setting

    Authors: Nathan A. Moore; Rebecca Williams; Matilde Mori; Beatrice Bertolusso; Gabrielle Vernet; Jessica Lynch; Peter Philipson; Thomas Ledgerwood; Stephen P. Kidd; Claire Thomas; Veronica Garcia-Arias; Michelle Young; Kordo Saeed; Kirsty Gordon; Nicholas Cortes

    doi:10.1101/2021.04.19.21252978 Date: 2021-04-22 Source: medRxiv

    Background: There is a lack of biomarkers validated for assessing clinical deterioration in COVID-19 MESHD patients upon presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of a range of biomarkers, including C-Reactive Protein HGNC ( CRP HGNC) and Procalcitonin (PCT) and Mid-Regional pro-adrenomedullin (MR-proADM), and White Cell Count to support prediction of clinical outcomes. Methods: Adult patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 MESHD via RT-qPCR were included. Biomarkers were measured in blood samples taken within 24 hours of admission and logistic regression and area under the receiver operating characteristic (AUROC) curves were used to predict disease progression. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, admission to critical care and non-invasive ventilation (NIV) use. Findings: A total of 135 adult patients were identified. Elevated levels of MR-proADM were shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular disease MESHD, renal disease MESHD and neurological disease MESHD. A significant association was also noted between raised MR-proADM and CRP HGNC concentrations and the requirement for critical care admission and non-invasive ventilation, when controlling for covariates. Interpretation: The measurement of biomarkers, particularly MR-proADM and CRP HGNC in patients with confirmed COVID-19 MESHD infection upon admission to secondary care shows significant potential to support clinicians in the early identification of those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions and treatment.

    Randomized, Comparative, Clinical Trial to Evaluate Efficacy and Safety of PNB001 in Moderate COVID-19 MESHD Patients

    Authors: Eric Lattman; Pradnya Bhalerao; ShashiBhushan BL; Neeta Nargundkar; Pornthip Lattmann; Sadasivan Pillai K; P.N. Balaram

    doi:10.1101/2021.04.16.21255256 Date: 2021-04-16 Source: medRxiv

    Objective: To evaluate the efficacy and safety of PNB001 a CCK-A HGNC agonist and CCK-B HGNC antagonist, a new chemical entity with anti-inflammatory and immune stimulation properties, along with Standard of Care (SOC) in patients with moderate COVID-19 MESHD infection. Design: Multi-center, randomized, parallel group, comparative, open label study. Setting: Two tertiary-care hospitals in India. Participants: Patients with laboratory-confirmed SARS-CoV-2 infection MESHD as determined by polymerase chain reaction (PCR) within 2 days of randomization, having pneumonia MESHD with no signs of severe disease MESHD (severe disease means SpO2<=94% on room air), and any two of the following signs or symptoms suggestive of COVID-19 MESHD: fever MESHD, cough MESHD, dyspnea MESHD, or hypoxia MESHD. Interventions: Patients were randomized 1:1 to receive PNB001 at an oral dose of 100 mg three times daily for 14 days with Standard of Care (PNB001+SOC) or only SOC. Main outcome measures: The primary endpoints were mean change in the 8-point WHO Ordinal Scale score from baseline by Day 14 and mortality rate by Day 28. The key secondary endpoints were percentage of patients showing change in clinical status using the ordinal scale, improvement in inflammatory segments in X-ray chest, reduction of days of hospitalization, duration of supplemental oxygen use, days to negative PCR for COVID-19 MESHD and change in inflammation MESHD markers Interlukin-6 ( IL6 HGNC) and C-reactive protein HGNC ( CRP HGNC) from baseline by Day 14. Results: A total of 40 (20 in PNB 001+SOC arm and 20 in SOC arm) patients were randomized and received treatment. The primary endpoint showed significant clinical improvement from baseline to Day 14 with PNB001+SOC (0.22 Vs 1.12; P=0.0421). One patient in PNB001+SOC arm and two patients in SOC arm died (1 Vs 2; HR: 2.0 [95%CI=0.18, 22.05]; P=0.5637) by Day 28. At the end of the treatment by Day 14, more patients achieved zero ordinal scale in PNB001+SOC arm (17 Vs 12; P=0.0766). In the PNB001+SOC arm, change in mean chest X-ray score showed significant improvement (2.05 Vs 1.16; P=0.0321), and more patients quickly showed complete improvement (10 Vs 7; HR: 1.48 [95%CI=0.64, 3.44]; P=0.4309). In the PNB001+SOC arm, patients needed shorter duration of hospitalization in days (9.45 Vs 9.80) and more patients attained earlier discharge from the hospital (19 Vs 15; P=0.0486) with respect to days. The mean duration of supplemental oxygen requirement in days was shorter (5.45 Vs 7.10) and complete withdrawal from supplemental oxygen was more frequent with PNB001+SOC compared to SOC by Day 14 (17 Vs 13; P=0.1441). All patients in both the arms had negative PCR by the end of the study (18 Vs 17; P=0.6265) by similar time (7.6 Vs 7.0). Exploratory analysis done for IL-6 HGNC, CRP HGNC, Neutrophil-Lymphocyte-Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Erythrocyte Sedimentation Rate (ESR) showed statistically significant reduction by Day 14 demonstrating PNB001's anti-inflammatory and immunomodulatory properties. Lymphocyte and neutrophil counts also improved by Day 14. 11 adverse events (AE) in 8 patients were observed with PNB001+SOC compared to 13 AEs in 10 patients with SOC; none of the AEs in PNB001+SOC arm were related to PNB001. The most common AE were tachycardia MESHD and acute respiratory distress syndrome MESHD; there were isolated cases of hepatic enzyme elevation and hyperglycemia MESHD. Overall, safety profile was similar between PNB001+SOC and SOC arms. Conclusions: PNB001 with standard of care showed significant clinical improvement in moderate COVID-19 MESHD patients when compared to standard of care and was well tolerated by moderate COVID-19 MESHD patients.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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