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MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    An Anti-CD6 Monoclonal Antibody SERO (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly TRANS Patients

    Authors: Danay Saavedra; Ana Laura Añé-Kourí; Naivy Sánchez; Lázaro Manuel Filgueira; Julio Betancourt; Carlos Herrera; Leniel Manso; Elibet Chavez; Armando Caballero; Carlos Hidalgo; Geydi Lorenzo; Meylan Cepeda; Carmen Valenzuela; Mayra Ramos; Kalet León; Zaima Mazorra; Tania Crombet

    doi:10.21203/rs.3.rs-32335/v1 Date: 2020-05-29 Source: ResearchSquare

    Background: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly TRANS with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease MESHD, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression MESHD is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumabis a humanized recombinant anti-CD6 monoclonal antibody SERO(MAb), with the ability of reducingserum interferon gamma(INF-γ), tumournecrosis factor alpha(TNFα) and IL-6. Based on these previous results in patients with psoriasis MESHD and rheumatoid arthritis MESHD rheumatoid arthritis HP, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients. Results: We show here a short kinetic of IL-6 serum SERO concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly TRANS with multiple comorbidities.We found that with one itolizumabdose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn’trise as compared to theirlow baseline levels.Conclusion: These findings suggest that itolizumabcould be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients.Trial registration: CECMED IIC RD-EC 179, RPCEC00000311. Registered 4May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En

    The Essential Role of Vitamin D in the Biosynthesis of Endogenous Antimicrobial Peptides May Explain Why Deficiency Increases Mortality Risk in COVID-19 Infections MESHD

    Authors: Patrick J. McCullough; Jeffrey Amend; William P. McCullough; Steven J. Repas; Jeffrey B. Travers; Douglas S. Lehrer

    id:10.20944/preprints202005.0265.v1 Date: 2020-05-16 Source: Preprints.org

    Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum SERO 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections MESHD are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum SERO 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum SERO 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis MESHD. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection MESHD, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections MESHD, in particular those from pandemic COVID-19.

    Lysosomotropic Active Compounds—Hidden Protection against COVID-19 / SARS-CoV-2 Infection MESHD?

    Authors: Markus Blaess; Lars Kaiser; Martin Sauer; Hans-Peter Deigner

    id:10.20944/preprints202005.0061.v1 Date: 2020-05-05 Source: Preprints.org

    The COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide in recent decades, and it is infecting and killing increasing numbers of people every day. In this paper, we discuss the possible relationships among lysosomotropism, increasing lysosomal pH, and the SARS-CoV-2 infection MESHD and disease MESHD process, and we deduce a possible approach for treatment and prophylaxis. Lysosomotropism is a biological characteristic of small molecules, such as (hydroxyl)chloroquine, amitriptyline, NB 06, or sertraline, which is present in addition to intrinsic receptor-mediated or enzymatic pharmacological effects. Lysosomotropic compounds affect prominent inflammatory messengers, such as IL1B, CCL4, CCL20, and IL6, as well as cathepsin L dependent viral entry (fusion) into host cells. Therefore, this heterogeneous group of compounds is a promising candidate for the prevention and treatment of SARS-CoV-2 infections MESHD, as well as influenza A infections MESHD and cytokine release syndrome MESHD (CRS) triggered by bacterial or viral infections MESHD. Patients who have already taken medications with lysosomotropic compounds for other pre-existing conditions may benefit from this treatment in the COVID-19 pandemic. Increased lysosomal pH levels play an important role in the disease MESHD process in common skin disorders, such as psoriasis MESHD and atopic dermatitis MESHD atopic dermatitis HP, thus suggesting that affected individuals might benefit from their particular conditions in the COVID-19 pandemic. We suggest data analysis of patients with these diseases MESHD, and who are treated with lysosomotropic compounds, and, if the results are promising, subsequent clinical testing of off-label therapy with clinically approved lysosomotropic compounds in the current COVID-19 pandemic and future influenza A pandemics.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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