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Preprint ARTICLE | doi:10.20944/preprints202003.0333.v1

Identification of Potent COVID-19 Main Protease (Mpro) Inhibitors from Natural Polyphenols: An in Silico Strategy Unveils a Hope against CORONA

Sevki Adem, Volkan Eyupoglu, Iqra Sarfraz, Azhar Rasul, Muhammad Ali

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; molecular docking; flavonoids

Online: 23 March 2020 (04:30:47 CET)

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Working Paper ARTICLE

Coronavirus Disease 2019 (COVID-19) During Pregnancy: A Case Series

Weiyong Liu, Qianli Wang, Qi Zhang, Ling Chen, Junbo Chen, Bo Zhang, Yanjun Lu, Shaoshuai Wang, Liming Xia, Lu Huang, Kai Wang, Lu Liang, Yongli Zhang, Lance Turtle, David Lissauer, Ke Lan, Ling Feng, Hongjie Yu, Yingle Liu, Ziyong Sun

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: pregnancy; neonate; COVID-19; SARS-CoV-2; vertical transmission

Online: 25 February 2020 (11:38:47 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0315.v1

Two Things about COVID-19 Might Need Attention

Xiaodong Jia, Chengliang Yin, Shanshan Lu, Yan Chen, Qingyan Liu, Junfan Bai, Yinying Lu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; adipose tissue; cancer; ACE2

Online: 23 February 2020 (10:30:06 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202206.0308.v1

A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

Michael Mörz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mRNA Vaccine; autopsy

Online: 22 June 2022 (07:53:57 CEST)

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Working Paper CASE REPORT

Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19)

Weiren Luo, Hong Yu, Jizhou Gou, Xiaoxing Li, Yan Sun, Jinxiu Li, Lei Liu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Novel coronavirus pneumonia; COVID-19; SARS-CoV-2; Pathology; Critical patient

Online: 27 February 2020 (12:30:45 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202402.1096.v1

Delayed Fatal Pulmonary Hemorrhage Following COVID-19 Vaccination: Case Report, Batch Analysis, And Proposed Autopsy Checklist

Nicolas Hulscher, Peter A. McCullough

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19 vaccination; Death; Autopsy; Pulmonary hemorrhage; Adverse events; Spike protein; Batch; Thrombosis; Safety

Online: 20 February 2024 (06:33:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0311.v1

Pathological Study of the 2019 Novel Coronavirus Disease (COVID-19) through Post-Mortem Core Biopsies

Sufang Tian, Yong Xiong, Huan Liu, Li Niu, Jianchun Guo, Meiyan Liao, Shu-Yuan Xiao

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; pathology; post-mortem biopsy

Online: 20 March 2020 (09:24:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints201803.0062.v1

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

Marianne J. Middelveen, Eva Sapi, Jennie Burke, Katherine R. Filush, Agustin Franco, Melissa C. Fesler, Raphael B. Stricker

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Lyme disease; Borrelia burgdorferi; Tickborne disease; Chronic infection; Spirochete culture

Online: 8 March 2018 (07:08:02 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202002.0424.v1

Insufficient Sensitivity of RNA Dependent RNA Polymerase Gene of SARS-CoV-2 Viral Genome as Confirmatory Test using Korean COVID-19 Cases

Soyoun Kim, Dong-Min Kim, Baeckseung Lee

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; Korean COVID-19; Wuhan Corona virus; real time PCR Ct Value; Sensitivity; False Negative

Online: 28 February 2020 (12:03:13 CET)

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Working Paper CASE REPORT

Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19)

Weiren Luo, Hong Yu, Jizhou Gou, Xiaoxing Li, Yan Sun, Jinxiu Li, Lei Liu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Novel coronavirus pneumonia; COVID-19; SARS-CoV-2; Pathology; Critical patient

Online: 27 February 2020 (16:06:23 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202005.0262.v1

C1-INH and the Contact System in COVID-19-Associated Coagulopathy

Timothy M. Thomson, Emily Toscano, Ernesto Casis, Rosanna Paciucci

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; coagulopathy; C1-INH

Online: 16 May 2020 (04:19:07 CEST)

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Working Paper CASE REPORT

Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19)

Weiren Luo, Hong Yu, Jizhou Gou, Xiaoxing Li, Yan Sun, Jinxiu Li, Lei Liu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Novel coronavirus pneumonia; COVID-19; SARS-CoV-2; Pathology; Critical patient

Online: 2 March 2020 (15:32:55 CET)

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Background Novel coronavirus pneumonia ( COVID-19) have emerged as major global health threats since December, 2019. Up to now, the histopathology of critical patient with COVID-19 remains largely undisclosed. Methods We here performed the whole lung biopsy, and described the pathological changes of one COVID-19 critical patient done with transplant by HE staining, immunohistochemistry and special staining including Masson staining, PAS staining and silver methenamin staining. Findings The whole lung tissue displayed diffuse congestive appearance or partly haemorrhagic necrosis on gross examination. The haemorrhagic necrosis was prominently present in outer edge of the right lobe of the right lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological lung changes showed bronchiolitis and alveolitis with proliferation, atrophy, desquamation and squamous metaplasia of epithelial cells. Massive pulmonary interstitial fibrosis, and partly hyaline degeneration, variable degrees of hemorrhagic pulmonary infarction. Small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma cells infiltrating into pulmonary interstitium. Atrophy, vacuolar degeneration, proliferation, desquamation and squamous metaplasia in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema fluid, desquamated epithelial cells, and inflammatory cells. We can also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Masson staining indicated massive pulmonary interstitial fibrosis. Immunohistochemistry results showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We show clinical pathology biopsy of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and the severity of this disease.

Preprint ARTICLE | doi:10.20944/preprints202004.0438.v1

Liver and COVID 19 Infection: A Very Preliminary Lesson Learnt from Histological Post-mortem Findings in 48 patients

Aurelio Sonzogni, Giulia Previtali, Michela Seghezzi, Maria Grazia Alessio, Andrea Gianatti, Lisa Licini, Pietro Zerbi, Luca Carsana, Roberta Rossi, Eleonora Lauri, Alessandro Pellegrinelli, Manuela Nebuloni

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Liver pathology; COVID 19 infection

Online: 24 April 2020 (10:53:36 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0220.v1

Pulmonary Pathology of Early Phase SARS-COV-2 Pneumonia

Sufang Tian, Weidong Hu, Li Niu, Huan Liu, Haibo Xu, Shu-Yuan Xiao

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: coronavirus; COVID-19 pneumonia; pathology; SARS-CoV-2

Online: 16 February 2020 (14:41:28 CET)

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Working Paper CASE REPORT

Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19)

Weiren Luo, Hong Yu, Jizhou Gou, Xiaoxing Li, Yan Sun, Jinxiu Li, Lei Liu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Novel coronavirus pneumonia; COVID-19; SARS-CoV-2; Pathology; Critical patient

Online: 9 March 2020 (10:31:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202006.0009.v1

Infodemic: How an Epidemic of Misinformation Could Lead to a High Number of the Novel Corona Virus Disease Cases in Uganda

Betty K. Nannyonga, Rhoda K. Wanyenze, Pontiano Kaleebu, John M. Ssenkusu, Freddie Sengooba, Tom Lutalo, Willford Kirungi, Fredrick Edward Makumbi, Henry Kyobe Bosa, Vincent A. Ssembatya, Henry Mwebesa, Diana Atwine, Jane Ruth Aceng, Yonas Tegegn Woldermariam

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: infodemic; misinformation; COVID-19

Online: 3 June 2020 (05:16:33 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0143.v1

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes

Massimiliano Bonafè, Francesco Prattichizzo, Angelica Giuliani, Gianluca Storci, Jacopo Sabbatinelli, Fabiola Olivieri

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; IL-6; inflamm-aging; immune senescence; host-directed therapies

Online: 9 April 2020 (08:38:22 CEST)

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Working Paper ARTICLE

The Rationale for a Multi-Step Therapeutic Approach Based On Antivirals and Drugs with Immunomodulatory Activity in Patients With Coronavirus-Sars2-Induced Disease of Different Severity

Sirio Fiorino, Maddalena Zippi, Claudio Gallo, Debora Sifo, Sergio Sabbatani, Roberto Manfredi, Edoardo Rasciti, Leonardo Rasciti, Enrico Giampieri, Ivan Corazza, Paolo Leandri, Dario de Biase

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS; Covid-19; Vitamins; Therapy

Online: 23 April 2020 (05:44:52 CEST)

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Working Paper ARTICLE

COVID-19, What Could Sepsis, Severe Acute Pancreatitis, Gender Differences and Aging Teach Us?

Claudio Gallo, Sirio Fiorino, Giovanni Posabella, Donato Antonacci, Antonio Tropeano, Emanuele Pausini, Carlotta Pausini, Tommaso Guarniero, Marco Zancanaro

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; Sepsis; Inflammation

Online: 19 July 2020 (15:11:24 CEST)

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Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).

Preprint CASE REPORT | doi:10.20944/preprints202209.0051.v1

A Case Report: Acute Myocardial Infarction, Coronal Arteritis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

Michael Mörz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mRNA Vaccine; autopsy

Online: 5 September 2022 (08:14:56 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202004.0009.v1

A Flexible Genome-Scale Resource of SARS-CoV-2 Coding Sequence Clones

Dae-Kyum Kim, Jennifer J. Knapp, Da Kuang, Patricia Cassonnet, Payman Samavarchi-Tehrani, Hala Abdouni, Ashyad Rayhan, Dayag Sheykhkarimli, Etienne Coyaud, Sylvie van der Werf, Caroline Demeret, Anne-Claude Gingras, Brian Raught, Yves Jacob, Frederick P. Roth

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; coronavirus; coding sequences; collections

Online: 2 April 2020 (04:15:54 CEST)

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Preprint REVIEW | doi:10.20944/preprints202003.0353.v1

In Search of Feasible Interventions for the Prevention and Cure of Novel Coronavirus Disease 2019

Sunil Kumar Verma

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; Severe Acute Respiratory Syndrome Coronavirus-2; Curcumin

Online: 24 March 2020 (03:16:22 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0546.v2

Aerosol Particles Laden with Viruses That Cause COVID-19 Travel Over 30m Distance

Boris Gorbunov

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; face masks; aerosol; infection transmission route; weather conditions; viral load; exposure; dose

Online: 21 May 2020 (04:05:50 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0307.v1

Bioinformatic Analysis Reveals That the Reproductive System is Potentially at Risk from SARS-CoV-2

Jiawei Zhang, Yuqi Wu, Rui Wang, Keshi Lu, Menjiang Tu, Huan Guo, Weijie Xie, Zizhen Qin, Shulin Li, Pei Zhu, Xiangwei Wang

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; ACE2; reproductive system; single-cell RNA-seq

Online: 21 February 2020 (08:09:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0220.v2

Pulmonary Pathology of Early Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients with Lung Cancer

Sufang Tian, Weidong Hu, Li Niu, Huan Liu, Haibo Xu, Shu-Yuan Xiao

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: coronavirus; COVID-19 pneumonia; pathology; SARS-CoV-2

Online: 2 March 2020 (01:34:58 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202206.0308.v2

A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

Michael Mörz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mRNA Vaccine; autopsy

Online: 25 August 2022 (03:54:58 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202205.0330.v1

Variant Allele of ALDH2, rs671 Associates with Attenuated Post-Vaccination Response in Anti-SARS-CoV-2 Spike Protein IgG: A Prospective Study in the Japanese General Population

Akiko Matsumoto, Megumi Hara, Mohammad Said Ashenagar, Mikiko Tokiya, Takeshi Sawada, Chiharu Iwasaka, Takuma Furukawa, Kyoko Kitagawa, Yasunobu Miyake, Yoshio Hirota

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: ALDH2; rs671; COVID-19; vaccine; immunogenicity

Online: 24 May 2022 (10:08:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202002.0447.v1

An Evolutionary RGD Motif in the Spike Protein of SARS-CoV-2 may Serve as a Potential High Risk Factor for Virus Infection?

Shijia Yan, Haixia Sun, Xianzhang Bu, Guohui Wan

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; ACE2; RGD; Spike protein; therapeutic drugs

Online: 28 February 2020 (16:26:53 CET)

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Preprint ARTICLE | doi:10.20944/preprints202003.0457.v1

Inhibition of Viral Macrodomain of COVID-19 and Human TRPM2 by losartan

Mohammad Sadegh Damavandi

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Viral Macrodomain; COVID-19; TRPM2; losartan; Bioinformatics

Online: 31 March 2020 (10:23:10 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0077.v2

The Pathophysiology of Virulence of the COVID-19

Joseph De Soto, Shazia Hakim, Frederick Boyd

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; native American Indian; treatment; ACE2 receptor; pathophysiology; virulence

Online: 15 April 2020 (08:08:52 CEST)

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Background: On Dec 19, 2019, the public health department of China reported that an outbreak of pneumonia was caused by a novel Coronavirus. The virulence of the new virus COVID-19 was much greater than either the SARs and MERSs viruses and on March 11, 2020, the World Health Department (WHO) declared a worldwide pandemic. Understanding the pathophysiology of virulence of the SARS-COV-2 virus is absolutely necessary for understanding the transmission, virulence factors, reduce risk factors, clinical presentation, predict outcomes of the disease and provide guidance for any current or future treatment protocols. Methodology: A comprehensive PubMed search was performed during December 20, 2019 and April 03, 2020, utilizing the words: Wuhan Virus, COVID-19, SARs coronavirus, ACE2, S-protein, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal. Results: The SARS-COV-2 virus is much more virulent than either the SAR’s or MER’s virus and its ability to cause serious disease inversely corresponds to the person’s ability to produce T-cells which declines linearly with age. The ACE2 receptor binding site does not vary among different ethnic groups but do in ACE-2 expression levels. This variance in expression level may explain for different infectivity rates among men and women and predict and explain different susceptibilities to infection by different ethnic groups. Furthermore, by understanding the underlying pathophysiology one can explain and provide guidance to the clinical effectiveness of any treatment. Conclusions: The underlying pathophysiology of COVID-19 explains not only the virulence, and clinical presentation, but, explains at a molecular level the comorbidity risk factors such as hypertension, sex, and age. Ethnic and anatomic expression patterns of ACE-2 and associated pathophysiology suggests that Native Americans and Asians may be particularly susceptible to this disease.

Working Paper ARTICLE

COVID-19 Perfect Storm (Part II): Role of Vitamins as Therapy or Preventive Strategy in Aged People

Sirio Fiorino, Claudio Gallo, Maddalena Zippi, Sergio Sabbatani, Roberto Manfredi, Renzo Moretti, Elisa Fogacci, Caterina Maggioli, Francesca Travasoni Loffredo, Enrico Giampieri, Ivan Corazza, Christoph Dickmans, Claudio Denitto, Michele Cammarosano, Michele Battilana, Paolo Emilio Orlandi, Francesco Del Forno, Francesco Miceli, Michela Visani, Giorgia Acquaviva, Paolo Leandri, Elio Jovine, Roberto Iovine, Dario de Biase

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS; CoV-2; COVID-19; vitamins; therapeutic strategy

Online: 18 May 2020 (12:51:05 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0238.v1

NETs By-products and Extracellular DNA May Play a Key Role in COVID-19 Pathogenesis: Incidence on Patient Monitoring and Therapy

Alain Thierry, Benoit ROCH

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Covid; NET; neutrophils; circulating DNA; therapy; innate immune response

Online: 15 April 2020 (09:55:34 CEST)

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Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.

Preprint REVIEW | doi:10.20944/preprints202006.0105.v1

COVID-19 and Recycled Wastewater Irrigation: A Review of Implications

Md. Moinul Hosain Oliver, Guna Alankerage Hewa, David Pezzaniti, Md. Ariful Haque, Shamsul Haque, Md. Manjurul Haque, Md. Moniruzzaman, Md. Mostafizar Rahman, Khokan K. Saha, Md. Nurul Kadir

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Recycled Wastewater; Irrigation; Sprinkler; Coronavirus; SARS-CoV-2

Online: 7 June 2020 (16:00:25 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202005.0429.v1

Mechanical Ventilation Stimulates Expression of the SARS-Cov-2 Receptor ACE2 in the Lung and May Trigger a Vicious Cycle

Sui Huang, Arja Kaipainen, Michael Strasser, Sergio Baranzini

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mechanical stress; vicious cycle; midkine; ARDS; GTEx

Online: 26 May 2020 (11:26:52 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0103.v1

Safe Laboratory Practices in the Light of Covid-19 Pandemic: Way Forward in a Resource Limited Setting

Kevin Odega, Ehijie Iyamah, Ephraim Ibadin, Festus Idomeh, Deborah odega

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Coronavirus; SARS-CoV-2; Medical Laboratory; Resource-limited setting, Good Laboratory Practice (GLP)

Online: 7 April 2020 (12:11:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0430.v1

Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 ‘‘Cytokine Storm’’

Mattia Vinciguerra, Silvia Romiti, Ernesto Greco

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: atherosclerosis; sars-cov-2; covid-19; pathogenesis of sars-cov-2

Online: 24 April 2020 (08:58:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201811.0395.v1

Rapid Diagnosis of Capnocytophaga canimorsus Septic Shock in an Immunocompetent Individual Using Real-Time Nanopore Sequencing

Seweryn Bialasiewicz, Tania P.S. Duarte, Son H. Nguyen, Vichitra Sukumaran, Alexandra Stewart, Sally Appleton, Miranda E. Pitt, Arnold Bainomugisa, Amy V. Jennison, Rikki Graham, Lachlan J.M. Coin, Krispin Hajkowicz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: nanopore sequencing; droplet digital PCR; Capnocytophaga canimorsus; diagnosis; sepsis

Online: 16 November 2018 (09:45:38 CET)

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Preprint ARTICLE | doi:10.20944/preprints201704.0102.v1

Age-Related Diseases as Vicious Cycles

Aleksey V. Belikov

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: aging; age-related disease; mortality rate; positive feedback loop; vicious cycle

Online: 18 April 2017 (02:45:04 CEST)

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Preprint REVIEW | doi:10.20944/preprints201702.0020.v1

Potential Modes of Intercellular Alpha-Synuclein Transmission

Dario Valdinocci, Rowan A. W. Radford, Sue Maye Siow, Roger S. Chung, Dean L. Pountney

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: alpha-synuclein; Parkinsons disease; dementia with Lewy bodies; multiple system atrophy; tunelling nanotube; glymphatic system; cell-to-cell spread

Online: 7 February 2017 (03:24:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints201610.0083.v1

UPEI-400, a Conjugate of Lipoic Acid and Scopoletin, Mediates Neuroprotection in a Rat Model of Ischemia/Reperfusion

Barry J. Connell, Monique C. Saleh, Desikan Rajagopal, Tarek M. Saleh

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: stroke; antioxidant; co-drug; animal model

Online: 20 October 2016 (08:46:38 CEST)

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Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Preprint REVIEW | doi:10.20944/preprints201703.0125.v1

Peptidylarginine Deiminases as Mediators of Microvesicular Release - Novel Therapeutic Interventions

Sigrun Lange, Sharad Kholia, Uchini Kosgodage, Mariya Hristova, John Hardy, Jameel M Inal

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Extracellular vesicles (EVs); Peptidylarginine deiminases (PADs); Chlor-amidine (Cl-Am); cancer; neurodegeneration; deimination; cytoskeleton; induced pluripotent stem cells (iPSCs); histone H3; epigenetics

Online: 16 March 2017 (17:54:15 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202004.0009.v2

A Flexible Genome-Scale Resource of SARS-CoV-2 Coding Sequence Clones

Dae-Kyum Kim, Jennifer J. Knapp, Da Kuang, Patricia Cassonnet, Payman Samavarchi-Tehrani, Hala Abdouni, Ashyad Rayhan, Dayag Sheykhkarimli, Etienne Coyaud, Sylvie van der Werf, Caroline Demeret, Anne-Claude Gingras, Brian Raught, Yves Jacob, Frederick P. Roth

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; coronavirus; coding sequences; collections

Online: 4 May 2020 (18:28:01 CEST)

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Preprint SHORT NOTE | doi:10.20944/preprints202004.0516.v1

Is There a Relationship Between Blood Group and COVID-19 Susceptibility?

Davide Golinelli, Erik Boetto, Maria Pia Fantini

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: ABO blood groups system; COVID-19; susceptibility; SARS-CoV-2; SARS

Online: 30 April 2020 (05:51:35 CEST)

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Working Paper ARTICLE

Epigallocatechin-3-Gallate Reduces Hepatic Oxidative Stress and Lowers CYP-Mediated Bioactivation and Toxicity of Acetaminophen in Rats

Hsien-Tsung Yao, Chien-Chun Li, Chen-Hui Chang

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: epigallocatechin-3-gallate; acetaminophen; cytochrome P-450; bioactivation; apoptosis; autophagy; hepatotoxicity

Online: 28 July 2019 (16:45:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0546.v1

Aerosol Particles Laden with COVID-19 Travel Over 30m Distance

Boris Gorbunov

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; face masks; aerosol; infection transmission route; weather conditions; viral load; exposure; dose

Online: 30 April 2020 (17:29:23 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0077.v1

The Pathophysiology of Virulence of the COVID-19 Virus

Joseph De Soto, Shazia Hakim, Frederick Boyd

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; native American Indian; treatment; ACE2 receptor; pathophysiology; virulence

Online: 7 April 2020 (02:40:24 CEST)

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Background: On Dec 19, 2019 it was reported by the public health department of China that an outbreak of pneumonia was caused by a novel Coronavirus. The virulence of the new virus COVID-19 was much greater than either the SARs or MERSs viruses and on March 11, 2020 the World Health Department (WHO) declared world -wide pandemic. Understanding the pathophysiology of virulence of the COVID-19 virus is absolutely necessary in understanding the transmission, virulence factors, reduce risk factors, clinical presentation, predict outcomes of the disease and provide guidance to any current or future treatment protocols. Methodology: A PubMed search was performed utilizing the words: Wuhan Virus, COVID-19, SARs coronavirus, ACE2, S protein, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal. Results: The COVID-19 virus is much more virulent than either the SARs or MERs virus and its ability to cause serious disease inversely corresponds to the person’s ability to produce T-cells which declines linearly with age. The ACE2 receptor binding site do not vary among different ethnic groups but do in expression levels. This variance in expression level may explain for different infectivity rates among men and women and predict and explain different susceptibilities to infection by different ethnic groups. Furthermore, by understanding the underlying pathophysiology one can explain and provide guidance to the clinical effectiveness of any treatment. Conclusions: The underlying pathophysiology of COVID-19 explains not only the virulence, and clinical presentation, but, explains at a molecular level the comorbidity risk factors such as hypertension, sex, and age. Ethnic and anatomic expression patterns of ACE-2 and associated pathophysiology suggests that Native Americans and Asians may be particularly susceptible to this disease.

Preprint ARTICLE | doi:10.20944/preprints201703.0162.v1

Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow-Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological Approaches

Muhammad Abu-Elmagd, Mansour A Alghamdi, Magdy Shamy, Mamdouh I Khoder, Max Costa, Mourad Assidi, Roaa Kadam, Haneen Alsehli, Mamdooh Gari, Peter Natesan Pushparaj, Gauthaman Kalamegam, Mohammed Al-Qahtani

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Particulate matter; BM-MSCs; cell proliferation; cell death; qRT-PCR; IPA

Online: 20 March 2017 (16:33:56 CET)

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Preprint REVIEW | doi:10.20944/preprints201901.0170.v1

Dysbiosis Promotes Gastric Diseases and Impede Therapies by Hijacking Gut Immune Homeostasis

Devinder Toor, Mishi Wsson, Chavi Goel, Naveen Kumar Kaushik, Prashant Kumar, Singh Sandhya, G. Karthikeyan, Anil Kumar, Hridayesh Prakash

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: gut microbiota; macrophages; TLR mimicry; immunoepigenetics; metabolism; sterile inflammation

Online: 17 January 2019 (03:05:26 CET)

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Preprint REVIEW | doi:10.20944/preprints201907.0211.v1

HIV-1: Tackling the Obstacles, Which Limit the Effectiveness of the CRISPR-Cas9 Gene Editing of the T Cell Co-Receptor, CCR5

Tatiana Hillman

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: HIV-1; CRISPR-Cas9; T-cells; lipid nanoparticles; gut-associated-lymphoid tissue; Co-receptors; Probiotics; GI Tract,; Gene Editing

Online: 18 July 2019 (09:51:34 CEST)

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HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of Zinc fingers, and most of all the application of CRISPR-Cas9 technology, has given researchers a new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. The CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR possibly curing more diseases as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of the HIV-1, inhibiting HIV-1 gene expression. Since 2013 several other researchers have blocked HIV replication and infection through the CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells that consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus can not bind to T-cells, blocking the initial attachment stage, discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improve the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission.

Preprint ARTICLE | doi:10.20944/preprints202006.0279.v2

COVID-19 Testing – Impact of Prevalence, Sensitivity, and Specificity on Patient Risk and Cost

Zoe C. Brooks, Saswati Das

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID19; risk; clinical; metrics; cost; false-positive; false-negative; prevalence; sensitivity; specificity

Online: 9 July 2020 (15:57:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202006.0279.v1

COVID-19 Testing – Impact of Prevalence, Sensitivity, and Specificity on Patient Risk and Cost

Zoe C. Brooks, Saswati Das

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID19; risk; clinical; metrics; cost; false-positive; false-negative; prevalence; sensitivity; specificity

Online: 21 June 2020 (15:12:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202006.0032.v1

Emergence of RBD and D614G Mutations in Spike Protein: An Insight from Indian SARS-CoV-2 Genome Analysis

VINAYAGAM SAMYUKTHA, VENKATESAN NAVEEN KUMAR

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; Spike protein; COVID-19; Mutation; hACE2 Receptor; Real-time PCR; Vaccine

Online: 4 June 2020 (08:48:03 CEST)

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Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

Preprint ARTICLE | doi:10.20944/preprints202002.0381.v2

Identification of 22 N-glycosites on Spike Glycoprotein of SARS-CoV-2 and Accessible Surface Glycopeptide Motifs: Implications on Vaccination and Antibody Therapeutics

Dapeng Zhou, Ruibing Qi, Wen Zhang, Xiaoxu Tian, Chao Peng

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV2; corona virus; glycopeptide; N-linked glycans; mass spectrometry; antibody; cryo-EM structure; crystal structures; epitope prediction

Online: 13 April 2020 (11:09:29 CEST)

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Preprint REVIEW | doi:10.20944/preprints201808.0155.v1

Targeting Amyloid Aggregation: An Overview of Strategies and Mechanisms

Sofia Giorgetti, Claudio Greco, Paolo Tortora, Francesco Antonio Aprile

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: amyloid diseases; biocomputing; drug design; natural antiamyloids

Online: 8 August 2018 (04:27:10 CEST)

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Preprint REVIEW | doi:10.20944/preprints201705.0071.v1

Neurophysiological Changes Induced by Chronic Toxoplasma gondii Infection

Ellen Tedford, Glenn McConkey

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Toxoplasma gondii; neurophysiology; host-parasite interaction, neuroimmune, testosterone, dopamine, catecholamine, glutamatergic

Online: 8 May 2017 (18:34:39 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201704.0078.v1

Diabetogenic Effects of Ochratoxin A in Female Rats

Firdevs Mor, Omur Sengul, Senay Topsakal, Mehmet Akif Kilic, Ozlem Ozmen

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Ochratoxin A, insulin, glucagon, glucose, rat plasma, pathology, immunohistochemistry

Online: 13 April 2017 (11:46:19 CEST)

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Preprint REVIEW | doi:10.20944/preprints202007.0142.v1

COVID-19: The Rollercoaster of Fibrin(ogen), D-dimer, von Willebrand Factor, P-selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Corlia Grobler, Jhade Bredenkamp, Mireille Grobbelaar, Sipho Maphumulo, Jaco Laubscher, Janami Steenkamp, Douglas Kell, Etheresia Pretorius

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; fibrin(ogen); D-dimer; von Willebrand Factor; P-selectin; bleeding; thrombocytopenia; thrombosis

Online: 8 July 2020 (10:44:08 CEST)

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Preprint REVIEW | doi:10.20944/preprints201706.0059.v1

Pathology of Adult and Paediatric Mitochondrial Myopathies

Rahul Phadke

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mitochondrial; muscle biopsy; ragged red; COX-negative; subsarcolemmal; immunohistochemistry

Online: 13 June 2017 (06:23:36 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202006.0115.v1

Capillary Regression, A Key Pathogenic Feature of COVID-19 Infection?

George E. Davis, Courtney T. Griffin

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: capillary regression; COVID-19; pro-inflammatory mediators; interleukin-1 beta; tumor necrosis factor; thrombin

Online: 9 June 2020 (04:12:30 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0279.v1

Chinese Clinical Studies for Pharmacological Treatments of Coronavirus Disease 2019 (COVID-19)

Ru Han, Yitong Wang, Monique Dabbous, Shuyao Liang, Tingting Qiu, Mondher Toumi

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; clinical studies; China; clinical trials; observational studies

Online: 16 April 2020 (13:47:49 CEST)

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Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1^st, 2020 and March 21^st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8^th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

Preprint ARTICLE | doi:10.20944/preprints201708.0080.v1

A Unique TGFB1-Driven Genomic Program Links Astrocytosis, Low-Grade Inflammation and Partial Demyelination in Periplaques of Spinal Cords from Progressive Multiple Sclerosis Patients

Serge Nataf, Marc Barritault, Laurent Pays

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: multiple sclerosis; neuroinflammation; astrocytes; myelin; bioinformatics

Online: 23 August 2017 (17:46:28 CEST)

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Preprint REVIEW | doi:10.20944/preprints202101.0520.v1

Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra

Pio Conti, Fabrizio Pregliasco, Rosa G. Bellomo, Carla E. Gallenga, Alessandro Caraffa, Spyros K. Kritas, Dorina Lauritano, Gianpaolo Ronconi

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mast cell; psoriasis; inflammation; cytokine; Il-37; IL-38; IL-1Ra

Online: 25 January 2021 (15:57:19 CET)

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Preprint ARTICLE | doi:10.20944/preprints202004.0296.v1

Collective Clustering Dynamics of SARS-COV-2 Particles

Arturo Tozzi, James F. Peters, Isabella Annesi-Maesano, Gennaro D'Amato

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; supernatant; sphere packing; electron microscopy; clustering

Online: 17 April 2020 (08:30:13 CEST)

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Working Paper REVIEW

COVID-19 Perfect Storm (Part I): Cytokine Release Syndrome in Aged People

Sirio Fiorino, Claudio Gallo, Maddalena Zippi, Sergio Sabbatani, Roberto Manfredi, Renzo Moretti, Elisa Fogacci, Caterina Maggioli, Francesca Travasoni Loffredo, Enrico Giampieri, Ivan Corazza, Christoph Dickmans, Claudio Denitto, Michele Cammarosano, Michele Battilana, Paolo Emilio Orlandi, Francesco Del Forno, Francesco Miceli, Michela Visani, Giorgia Acquaviva, Paolo Leandri, Elio Jovine, Roberto Jovine, Dario de Biase

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS; CoV-2; COVID-19; immune system; cytokine

Online: 18 May 2020 (12:46:48 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202003.0338.v2

The Rational for Administration of ACE2 Pathway Inhibitors in Patients Infected by SARS-CoV-2: Devising an Administration Strategy

Loris Zamai

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Severe Acute Respiratory Syndrome Coronavirus-2; (soluble) ACE2; eosinophil; asthma; IL-10; IL-6; Lung fibrosis; Angiotensin; hypoxia; infarction; hypertension; hypercapnic acidosis; hypoxia; infarction; hypertension

Online: 24 March 2020 (06:47:18 CET)

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Preprint REVIEW | doi:10.20944/preprints202004.0182.v1

COVID-19 and Crosstalk between the Hallmarks of Aging

Shabnam Salimi, John M. Hamlyn

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; pandemic; co-morbidity; aging; hallmarks of aging; anti-aging

Online: 12 April 2020 (04:52:44 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201801.0021.v1

A New Biochemical Approach to Detect Oxidative Stress in Infertile Women Undergoing Assisted Reproductive Technology Procedures

Matteo Becatti, Rossella Fucci, Amanda Mannucci, Victoria Barygina, Marco Mugnaini, Luciana Criscuoli, Claudia Giachini, Francesco Bertocci, Rita Picone, Paolo Evangelisti, Francesca Rizzello, Cinzia Cozzi, Niccolò Taddei, Claudia Fiorillo, Maria Elisabetta Coccia

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: oxidative stress; in vitro fertilization (IVF); infertile women; follicular fluid (FF); granulosa cells

Online: 3 January 2018 (06:37:39 CET)

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Preprint ARTICLE | doi:10.20944/preprints202005.0364.v1

The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak

Ibrahim Y. Hachim, Mahmood Y. Hachim, Iman Mamdouh Talaat, Vanessa M. López-Ozuna, Narjes Saheb Sharif-Askari, Rabih Halwani, Qutayba Hamid

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; gender; transcriptomics; RAS; hydrolase activity; sex-based immunological differences

Online: 23 May 2020 (06:03:25 CEST)

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Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

Working Paper ARTICLE

Preventive, Mitigating and Treatment Strategies for Containing or Ending the COVID-19 Pandemic

Jianqing Wu, Ping Zha

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: coronavirus; COVID-19; viral reproduction; immune response; low temperature injury; lung damages; cold flu influenza; deep breathing exercises; diet; emotion stress; lifestyle

Online: 4 March 2020 (05:30:58 CET)

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To understand great disparities in disease outcomes between CIVID-19 patients, we explore infection and host responses in kinetics. From existing data, we deduced a model that the lungs are damaged by rapidly rising flow resistance as a result of retaining white blood cells in lung tissues. The retention of white blood cells is initially triggered by viral infection but aggravated by injuries caused by low temperature. Lungs are initially damaged by fluid leakage, rapidly followed by extruding blood into alveolar spaces. The step of blood extruding is predicted to take place in a very short time. Our simulations show that as little as 0.1% retention of white blood cells in the lungs can lead to their failure in 5 to 10 days. The small degrees of imbalance implies that this imbalance could be corrected by a large number of factors that are known to reduce flow resistance. The model implies that the top priority is maintaining blood micro-circulation and preserving organ functions in the entire disease course, especially after the virus has spread the whole lungs. From exploring a large number of hypothetical infection modes, we propose preventive, mitigating and treatment strategies for ultimately ending the pandemic. The first strategy is avoiding exposures that could result in widespread damages to lungs and taking post exposure mitigating measures that would reduce disease severity. The second strategy is reducing death rate and disability rate from the current levels to one tenth for infected patients by using multiple factors health optimization method. The double reduction strategies are expected to generate a series of chain reactions that favor mitigating or ending the pandemic. Some reactions include a big reduction of the amount of viral discharges from infected patients into the air, the avoidance of panic, chronic stress and emotional distress, and cross-infections which are expected in quarantines. The double reductions would have a final effect of ending the pandemic.

Preprint ARTICLE | doi:10.20944/preprints201805.0409.v1

New Methodology for Rapid Formation and Prevention of Advanced Glycation end Products (AGEs) In Vitro Coupled with the Hypoxanthine/Xanthine Oxidase Assay System

Samuel Marques, Teresa Trevisan, Carlos Maia, Andrea Breuer, Robert Owen

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: advanced glycation end products; glyoxal; hypoxanthine/xanthine oxidase; methyl glyoxal; RCS-trapping

Online: 28 May 2018 (13:28:19 CEST)

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Preprint REVIEW | doi:10.20944/preprints202003.0434.v1

Crucial Aspects of the Management of Solid Organ Transplant Patient with COVID-19: A Narrative Review

Antonio Romanelli, Silvia Mascolo

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: solid-organ transplantation; COVID-19; immunosuppression

Online: 29 March 2020 (11:20:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201805.0359.v1

Pathogenicity of Endocrine Dysregulation in Autism

Adam J. Swierczynski

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: autism spectrum disorder; endocrine; estrogen; immune activation; melanin concentrating hormone

Online: 25 May 2018 (10:37:23 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0385.v1

Consumptive Coagulopathy and Thrombosis during Severe COVID-19 Infection: Potential Involvement of VWF/ADAMTS13

Upendra K. Katneni, Aikaterini Alexaki, Ryan Hunt, Tal Schiller, Michael DiCuccio, Paul W. Buehler, Juan C. Ibla, Chava Kimchi-Sarfaty

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; Thrombosis; Inflammation; ADAMTS13; Von Willebrand Factor

Online: 24 May 2020 (16:17:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0310.v1

Parametric Nasopharyngeal Swab for Sampling COVID-19 and Other Respiratory Viruses: Open Source Design, SLA 3-D Printing and UV Curing System

Nicole Gallup, Adam M. Pringle, Shane Oberloier, Nagendra G. Tanikella, Joshua M. Pearce

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: open hardware; COVID-19; medical hardware; nasopharyngeal swab; nasal swab; UV curing; SLA; RepRap; 3-D printing; additive manufacturing

Online: 19 May 2020 (04:21:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202009.0029.v1

Risk of COVID-19 on Diabetes Mellitus and Hypertension

Abdullahi Aborode, Ademola Aiyenuro, Samuel Ogunsola, Victor Adesewa, Monsour Zakariyah

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: diabetes mellitus; hypertension; obesity; Coronavirus; mechanism; COVID-19; viral interaction

Online: 2 September 2020 (05:37:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202009.0280.v1

Altered Spatial Composition of the Immune Cell Repertoire in the Bone Marrow Stem Cell Niche in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia

Marcus Bauer, Christoforos Vaxevanis, Haifa Kathrin Al-Ali, Nadja Jaekel, Christin Le Hoa Naumann, Judith Schaffrath, Achim Rau, Barbara Seliger, Claudia Wickenhauser

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: MDS; immune cell repertoire; prognosis; multiplex immunohistochemistry; stem cell niche

Online: 13 September 2020 (11:51:13 CEST)

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Working Paper ARTICLE

COVID-19: Role of the Inflammasome

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

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; Inflammasome; Interleukin 1β; Inflammation; Innate Immune System

Online: 12 July 2020 (08:17:56 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202005.0006.v1

COVID-19: Probing the Possibility of Transmission in Animal Kingdom

Tawsif Ahmed Kazi, Suranjita Mitra, Bidhan Chandra Mukhopadhyay, Rajarshi Bhattacharya, Sukhendu Mandal, Swadesh Ranjan Biswas

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: 2019-nCoV; intermediate host; ACE2 receptor; COVID-19

Online: 2 May 2020 (12:11:38 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202203.0169.v1

Vaccines Associated Cardiac Adverse Events, including SARS-CoV-2 Myocarditis, Elevated Histamine Etiology Hypothesis

Darrell Ricke

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; adverse events; histamine intolerance; myocarditis; pericarditis; tachycardia

Online: 11 March 2022 (12:07:26 CET)

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Preprint REVIEW | doi:10.20944/preprints201805.0396.v1

Smart Wound Dressings for Diabetic Chronic Wounds

Elizabeth Gianino, Craig Miller, Jordon Gilmore

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: diabetes; chronic wounds; smart wound dressing; biochemical sensor

Online: 28 May 2018 (10:22:39 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201806.0261.v1

Searching for Perfect Marker - Differences and Dependencies in Serum Levels of Renalase, KIM-1, MCP-1, Calbindin and GST-Pi in Patients with Diabetes, Glomerulonephritis and Congenital Defects of the Kidney

Natalia Maria Serwin, Magda Wiśniewska, Edyta Skwirczyńska, Karol Serwin, Oskar Wróblewski, Barbara Dołęgowska

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: renalase; KIM-1; calbindin; MCP-1

Online: 15 June 2018 (14:53:54 CEST)

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Diagnosis of kidney diseases has recently become more comprehensive and accurate by using new renal markers. Despite the fact that creatinine and cystatin c have been sufficient in determining kidney function, they did not indicate the exact site of the damage and they were often insufficient in predicting the course of the disease. Aim of the study was to evaluate the potential correlations and differences in levels of six factors related to kidney function and injury: kidney injury molecule-1 (KIM-1), ncalbindin (CALB), glutathione S-transferase Pi (GST-Pi), calbindin and monocyte chemoattractant protein-1 (MCP-1), between renal patients with diabetic nephropathy (DM), congenital defects (CD) of the kidney and glomerulonephritis (GN). Study involved 75 patients: 49 with diabetic nephropathy, 12 with congenital defects and 14 with glomerulonephritis. Levels of renalase was measured using immunoenzymatic tests. Levels of other markers: calbindin, glutathione-S-transferase (GST-pi), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were analyzed using Kidney Toxicity-1 Panel and BioPlex system, designed for analyses in urine and optimized by us for serum.From all analyzed markers, only levels of KIM-1 differed significantly between any subgroups, and that was for CD and DM. Renalase correlated significantly negatively with creatinine and positively with all other markers, apart from MCP-1. Obtained results indicate, that serum renalase, KIM-1, calbindin and GST-pi are related to kidney function, with KIM-1 being the most exact, while MCP-1 levels are unrelated to creatinine and glucose levels, does not differ between patients with diabetic nephropathy and other subgroups, and therefore seem to be independent of diabetes. Also, serum-optimized Kidney Toxicity Panel 1 kit for determination of selected markers gave results similar to previous ones and therefore the method can be valuable in determination of analyzed factors.

Preprint REVIEW | doi:10.20944/preprints202005.0204.v1

A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models and Anti-Viral Interventions

Sabarinath Neerukonda, Upendra Katneni

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; animal models; anti-virals

Online: 12 May 2020 (05:45:58 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202003.0338.v3

Yin-Yang Balance of ACE/ACE2 Pathways: The Rational for Administration of ACE2 Pathway Inhibitors in Patients Infected by SARS-CoV-2

Loris Zamai

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Severe Acute Respiratory Syndrome Coronavirus-2; (soluble) ACE2; eosinophil; asthma; IL-10; Lung fibrosis; hypercapnic acidosis; hypoxia; infarction; hypertension; cardiac dysfunction; respiratory distress; coagulopathy; Angiotensin; renin; Ang (1-7); Ang (1-9); Mas receptor; AT2 receptor

Online: 6 May 2020 (04:40:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0418.v1

Introducing the Q-strip to Quantitatively Measure Nocturnal Perspiration as a Parameter and Predictor: A Review of Literature

Kasper Jolink, Loussi Bedrosian

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Diagnosis; Health sensing system; Nocturnal perspiration; Parameter; Pathology; Predictor; Q-strip; Subjective measurement; Sweat pattern; Symptoms; Prodromal; biomarker

Online: 23 April 2020 (15:26:39 CEST)

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Working Paper ARTICLE

Treatment Strategies for Reducing Damages to Lungs In Patients with Coronavirus and Other Infections

Jianqing Wu, Ping Zha

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: coronavirusl; SARS; MERS; viral reproduction; immune response; lung infections; lung damages; cold flu Fluenza; deep breath exercises; diet; emotion stress; lifestyle

Online: 9 February 2020 (17:43:00 CET)

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Preprint REVIEW | doi:10.20944/preprints202006.0183.v1

Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?

Ligong Lu, Hui Zhang, Meixiao Zhan, Jun Jiang, Hua Yin, Danielle Dauphars, Shi-You Li, Yong Li, You-Wen He

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; mortality; cytokine storm; cytokine release syndrome; chemokine; inflammation; immunopathology; IL-6; IL-1; CCL2; CCL5

Online: 14 June 2020 (15:44:38 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201902.0199.v1

Sleep Impairment at the Time of First Diagnosis in Patients with Seronegative Elderly-Onset Rheumatoid Arthritis and in Patients with Polymyalgia Rheumatica

Ciro Manzo, Alberto Castagna

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: polymyalgia rheumatica; elderly-onset rheumatoid arthritis; sleep impairment; seronegative rheumatoid arthritis; elderly patients

Online: 21 February 2019 (09:55:22 CET)

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Background: Differential diagnosis between polymyalgia rheumatica (PMR) and seronegative elderly-onset rheumatoid arthritis (SEORA) is not easy, to the point that in the past they were considered the same entity. In these patients, sleep disorders have been scarcely assessed, and considered as expression of mood disorders such as depression and anxiety. Methods: In 38 Caucasian elderly patients (median age: 73.9 ± 8.06 years) consecutively referred to two outpatient clinics from January to May 2018 with diagnosis of PMR and SEORA, sleep impairment was assessed using the Medical Outcomes Study-Sleep scale (MOS-SS). Depression and anxiety were assessed using the Neuropsychiatric Inventory (NPI) score, with point 0 for absent and point 3 for severe. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Patients taking medications used to treat sleep disturbance or that could favor sleep disturbances were excluded. The study was approved by the local ethics committee and carried out in accordance with the Helsinki Declaration, revised 2013. Every patient signed an informed consent form at the time of the first visit. Results: MOS-SS total point in PMR patients was significantly higher than in SEORA patients (47.60 ± 8.4 vs 28.26 ± 12.4; P = 0.000). After six-month therapy with prednisone (12.5–15 mg/day, followed after 4 weeks by gradual tapering), MOS-SS total point improved in the two groups of patients, with no significant difference (17.0 ± 6.2 vs 17.8 ± 4.2; P = 0.644). No correlation was found between MOS-SS and comorbidities, and between MOS-SS, anxiety or depression. Conclusions: Our data suggest that the assessment of sleep impairment could be very useful in the differential diagnosis between PMR and SEORA. Up today, the reasons why patients with PMR have—at the time of diagnosis—a sleep impairment higher than SEORA are speculative. Further ad hoc complementary studies in multicenter cohorts are needed.

Preprint REVIEW | doi:10.20944/preprints202006.0339.v1

New Coronavirus Disease (COVID-19): Clinical Symptoms Other Than Pneumonia with Emphasis on Thrombosis

Takuma Hayashi, Kaoru Abiko, Masaki Mandai, Nobuo Yaegashi, Ikuo Konishi

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: ACE2; COVID-19; SARS-CoV-2; alveolar macrophage; thrombus; thrombosis

Online: 28 June 2020 (10:34:52 CEST)

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Preprint REVIEW | doi:10.20944/preprints201909.0079.v1

Current Status of Stem Cell Therapy for Thromboangiitis Obliterans (Buerger's Disease)

Hassan Peyvandi, Biraja C. Dash, Sifon U. Ndon, Kyle Steven Gabrick, Athena Alipour Alipour, John A. Persing, Henry C. Hsia

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Thromboangiitis Obliterans; inflammation; angiogenesis; immunomodulation; pluripotent stem cell; mesenchymal stem cell

Online: 7 September 2019 (00:31:05 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201905.0225.v1

Use of GeneXpert and the Role of an Expert Panel in Improving Clinical Diagnosis of Smear-Negative Tuberculosis Cases

Jovilia Abong, Victoria Dalay, Ivor Langley, Ewan Tomeny, Danaida Marcelo, Victor Mendoza, Anna Marie Celina Garfin, S. Bertel Squire, Charles Yu

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: GeneXpert; TB Expert Panel; Smear Negatives; Clinically Diagnosed TB; TB DOTS; Chest X-ray

Online: 17 May 2019 (11:18:34 CEST)

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Working Paper ARTICLE

COVID-19: Role of the Interferons

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

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS CoV-2; IFN-⍺; IFN-β; IFN-λ

Online: 2 August 2020 (11:31:40 CEST)

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COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. 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 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 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, closely related to COVID-19 disease, 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.

Preprint REVIEW | doi:10.20944/preprints201809.0533.v1

Virulence Effectors of Pathogenic Mycoplasmas

Meghan A. May, Daniel R. Brown

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mycoplasma; virulence effectors; pathogenesis

Online: 27 September 2018 (05:54:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201811.0310.v1

Computational Topology Techniques Help to Solve a Long-Lasting Forensic Dilemma: Aldo Moro’s Death

James F. Peters, Arturo Tozzi

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: tessellation; forensic picture; bullets; homology; proximity

Online: 13 November 2018 (10:41:14 CET)

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Preprint ARTICLE | doi:10.20944/preprints202012.0094.v3

“Clinician’s Probability Calculator” to Convert Pre-Test to Post-Test Probability of COVID-19, Based on Method Validation from Each Laboratory

Zoe Brooks, Saswati Das, Tom Pliura

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-COV-2; False-Positive; False-Negative; Likelihood Ratio; Probability; Calculator; Interpretation

Online: 3 March 2021 (10:08:27 CET)

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Preprint REVIEW | doi:10.20944/preprints202009.0076.v1

Why COVID-19 Transmission is More Efficient and Aggressive than Viral Transmission in Previous Coronavirus Epidemics?

Fatma Elrashdy, Elrashdy M. Redwan, Vladimir N Uversky

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: severe acute respiratory syndrome coronavirus 2; SARS-CoV-2; coronavirus disease 2019; COVID-19; viral infection; virus-host interaction

Online: 4 September 2020 (03:19:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0104.v1

Investigation of the Health Effects of Workers Exposed to Respirable Crystalline Silica during Outdoor and Underground Construction Projects in Greece

Dimitrios Keramydas, Petros Bakakos, Manos Alchanatis, Ioannis Konstantakopoulos, Petros Papalexis, Kyriaki Tavernaraki, Vasileios Dracopoulos, Antonios Papadakis, Eugenia Pantazi, Nektaria Sidiropoulou, Georgios Chelidonis, Elias Chaidoutis, Theodoros C. Constantinidis, Dimosthenis Chochlakis, Nikolaos Kavantzas, Efstratios Patsouris, Andreas Ch. Lazaris

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: silicosis; silicon powder; crystalline silica (SiO2); construction workers; occupational exposure; occupational exposure limit; occupational hygiene

Online: 6 March 2020 (04:25:53 CET)

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Preprint ARTICLE | doi:10.20944/preprints202009.0390.v1

A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2

Cecy Xi, Arianna Arianna Di Fazio, Naveed Nadvi, Karishma Patel, Michelle Xiang, Hui Emma Zhang, Chandrika Deshpande, Jason Low, Xiaonan Trixie Wang, Yiqian Chen, Brenna Osborne, Ana Julia Vieira de Ribeiro, Geoffrey McCaughan, Bret Church, Joel Mackay, Mark Gorrell

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Recombinant protein; Protease; DPP4; Covid-19

Online: 17 September 2020 (08:44:17 CEST)

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Preprint REVIEW | doi:10.20944/preprints202009.0420.v1

SARS-CoV-2 S Protein Binding hACE2: Viral Entry, Pathogenesis, Prognosis, and Potential Therapeutic Targets

Lobna Al-Zaidan, Sarra Mestiri, Afsheen Raza, Maysaloun Merhi, Varghese Inchakalody, Queenie Fernandez, Nassiba Taib, Shahab Uddin, Said Dermime

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; ACE2 receptor; spike glycoprotein; S glycoprotein immunogenic sequences; ACE2 polymorphism

Online: 18 September 2020 (04:56:02 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0525.v1

The Epidemiology, Evolution, Transmission and Therapeutics of COVID-19 Outbreak: An Update on the Status

Karan Singh Labana, Amit Kumar Mittal, Akash Gujral

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; evolution of SARS-CoV-2; replication; emerging disease 2019 and diagnostic tools

Online: 30 April 2020 (10:39:54 CEST)

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans that is known as coronavirus disease 2019 (COVID19). The first outbreak of the disease was initially documented in Wuhan, Hubei Province, China in late December 2019 where people had experienced SARS pneumonia-like symptoms with unknown etiology. Since then it has been observed that COVID-19 positive patients have been showing mild to severe upper respiratory illness symptoms. The type of virus is known to make its transfer from animals to humans and for the concerned virus; researchers have claimed its origin from bat coronavirus at whole-genome level with a 96 % sequence identity. The COVID-19 virus is very contagious and communicable in nature and has been spread throughout the globe since its first outbreak in China. On March 9, 2020, WHO declared it as a Pandemic, and within a month it was already reported to have shown its presence in 213 countries and territories or areas. As of April 29, 2020, this novel virus infected 3,218,183 people and caused 228,029 mortalities worldwide with a variable mortality rate from 3-13 % across the planet and also varied by age and gender. Diagnosis of the disease is a key component in understanding and controlling the spread of the virus and several techniques have been devised including RT-PCR, ELISA, and sequencing-based approaches. To cure COVID-19 patients as of now we do not have proven to be a safe and effective treatment. Therapeutic options currently under investigation in various parts of the world. However, there are various effective therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2. Boosting the immune system can also help to prevent and spread of COVID-19 using various medication and exercises. In this review, our goal to summarize and discussed the present scientific advancements to fight against this novel pandemic.

Preprint REVIEW | doi:10.20944/preprints202009.0579.v1

Rabies as a Public Health Concern in India – A Historical Perspective

Sreejith Radhakrishnan, Abi Tamim Vanak, Pierre Nouvellet, Christl A. Donnelly

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: stray dogs; Pasteur Institute; vaccination; colonial; British India; Civil Veterinary Department

Online: 24 September 2020 (11:13:30 CEST)

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Medicine and Pharmacology