!!Biomedical research

[Sir Stephen Holgate|Member/Holgate_Stephen_Townley], in collaboration with others, published a paper in The Lancet titled ‘Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial’. The paper assesses the efficacy and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19. [Read more|https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30511-7/fulltext].
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[Sir Stephen Holgate|Member/Holgate_Stephen_Townley], in collaboration with others, published a paper titled ‘Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed’. The paper considers the potential role of anti-TNF therapy. [Read more|https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)30858-8/fulltext].
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[Sir Stephen Holgate|Member/Holgate_Stephen_Townley], in collaboration with others, published a paper in PubMed.gov titled ‘Risk Predictors and Symptom Features of Long COVID Within a Broad Primary Care Patient Population Including Both Tested and Untested Patients’. This study reports the factors and symptom features predicting long COVID in a broad primary care population. [Read more|https://pubmed.ncbi.nlm.nih.gov/34408531].
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[Giuseppe Novelli|Member/Novelli_Giuseppe] MAE, in collaboration with others, published a paper in ''Nature Immunology'' titled [A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection|https://www.nature.com/articles/s41590-021-01030-z]. The paper proposes a strategy for identifying, recruiting, and genetically analysing individuals who are naturally resistant to SARS-CoV-2 infection. [Read more|https://www.nature.com/articles/s41590-021-01030-z].
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[Giuseppe Novelli|Member/Novelli_Giuseppe] MAE, in collaboration with others, has published the following papers:

*‘Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations’. The paper provides a general framework for enhancing antiviral therapies against COVID-19 and related viral threats, a strategy which can be applied to virtually any antibody drug. [Read more|https://www.sciencedirect.com/science/article/pii/S0022283621004101?via%3Dihub].

*‘X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19’. The paper, published in Science Immunology, reports very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. [Read more|https://www.science.org/doi/10.1126/sciimmunol.abl4348].

*‘A focus on the spread of the delta variant of SARS-CoV-2 in India’ published in the Indian Journal of Medical Research. [Read more|https://journals.lww.com/ijmr/Fulltext/2021/05000/A_focus_on_the_spread_of_the_delta_variant_of.4.aspx].
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[Miklos Kellermayer|Member/Kellermayer_Miklós] MAE, in collaboration with others, has published a paper in ACS Publications, titled ‘Topography, Spike Dynamics, and Nanomechanics of Individual Native SARS-CoV-2 Virions’. In this paper, the topographical structure and nanomechanical properties of the native, unfixed SARS-CoV-2 virion are explored for the first time. The paper finds that the virion is quite resilient and is able to recover from multiple (up to one hundred) consecutive mechanical interventions. [Read more|https://pubs.acs.org/doi/10.1021/acs.nanolett.0c04465].
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[Ole Petersen|Member/Petersen_Ole], in collaboration with Julia V Gerasimenko and Oleg V Gerasimenko, published a paper in Function titled ‘SARS-CoV-2 S protein subunit 1 (S1) elicits Ca2+ influx – dependent Ca2+ signals in pancreatic stellate cells and macrophages in situ’. The paper finds that S1-elicited Ca2+ signals in the pancreatic stellate cells and endogenous macrophages may play an important part in the development of the inflammatory process of acute pancreatitis, which is similar to what is seen in COVID-19. [Read more|https://academic.oup.com/function/article/3/2/zqac002/6518286].
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[Ole H Petersen|Member/Petersen_Ole] FRS MAE, in collaboration with others, has published a paper in ''Physiological Reviews'' titled ‘The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas’. One of the sections deals with cytokine and bradykinin storms, which are common to COVID-19 and acute pancreatitis. Similar therapeutic approaches, outlined in the article, may work for both diseases. [Read more|https://journals.physiology.org/doi/abs/10.1152/physrev.00003.2021].

[Jean-Pierre Changeux|Member/Changeux_Jean-Pierre] MAE (in collaboration with Zahir Amoura, Felix A. Rey and Makoto Miyara) published a paper titled ‘''A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications''’. The paper hypothesizes that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection. [Read more|http://aecardiffknowledgehub.wales/wp-content/uploads/2021/03/CRBIOL_2020__343_1_33_0.pdf].

[Paul Morgan|Member/Morgan_Bryan_Paul] MAE, in collaboration with others, has published the following papers:
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*‘''[Complement Inhibition with the C5 Blocker LFG316 in Severe COVID-19|https://www.atsjournals.org/doi/10.1164/rccm.202007-2778LE]''’. This paper reports on the contribution of complement activation and impact of complement blockade in severe COVID-19. 

*‘''[Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens|https://journals.sagepub.com/doi/full/10.1177/0004563220981106]''’. This paper explores the performance of a scaleable and cost-effective assay protocol in DBS specimens using an existing national newborn screening laboratory infrastructure. 

*‘''[Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report|https://www.nature.com/articles/s41467-020-19761-2]''’. This paper reports the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). 
*‘[Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients: An observational cohort study|https://pubmed.ncbi.nlm.nih.gov/33497420]’. This paper describes the humoral responses in a cohort of hospitalised COVID-19 patients shortly following the onset of symptoms.

[Vincenzo Greco|Member/Greco_Vincenzo] MAE published a paper titled ‘Transmission of airborne virus through sneezed and coughed droplets’ (in collaboration with Santosh K. Das, Jan-e Alam and Salvatore Plumari). The paper discusses the evolution of droplets in space and time under varying external conditions of temperature, humidity, and wind flow. This paper offers useful information for preventing the spread of other types of droplets containing microorganisms. [Read more|https://aip.scitation.org/doi/10.1063/5.0022859].
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[Peter Hegyi|Member/Hegyi_Péter] MAE (in collaboration with Czumbel, Kiss, Farkas, Mandel, A. Hegyi, Nagy, Lohinai, Szakács, Steward and Varga) published the paper titled ‘Saliva as a Candidate for COVID-19 Diagnostic Testing: A Meta-Analysis’. This study offers evidence for saliva tests as a promising alternative to nasopharyngeal swab tests for COVID-19 diagnosis. [Read more|https://www.frontiersin.org/articles/10.3389/fmed.2020.00465/full].
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[Peter Hegyi|Member/Hegyi_Péter] MAE (in collaboration with Földi, Farkas, Kiss, Zádori, Váncsa, Szakó, Dembrovszky, Solymár, Bartalis, Szakács, Hartmann, Pár, Erõss, Molnár, Szentesi) published the paper titled ‘Obesity is a risk factor for developing critical condition in COVID-19 patients: A systematic review and meta-analysis’. The authors examined obesity as a risk factor for critical COVID-19 patients. This is the first meta-analysis about this topic. 
[Read more|https://onlinelibrary.wiley.com/doi/10.1111/obr.13095].
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[José López-Barneo|Member/López-Barneo_José] MAE, in collaboration with others published a paper titled ‘Is carotid body infection responsible for silent hypoxemia in COVID-19 patients?’. The authors propose a mechanism that may explain the low levels of oxygen in the bloodstream of patients with severe COVID-19. [Read more|https://academic.oup.com/function/article/2/1/zqaa032/5998649].
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[Sylviane Muller|Member/Muller_Sylviane] MAE and others published a paper titled ‘''Autophagy as an emerging target for COVID-19: lessons from an old friend, chloroquine''’.  Autophagy is the body’s mechanism to degrade and recycle old cellular components (organelles, proteins and cell membranes). The authors discuss how chloroquine (CQ) and hydroxychloroquine (HCQ) inhibit autophagy and could have potential therapeutic value in the treatment of COVID-19 patients. [Read more|https://www.tandfonline.com/doi/full/10.1080/15548627.2020.1779467].
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[Sylviane Muller|Member/Muller_Sylviane] MAE in collaboration with others published a paper titled ‘''[Neutrophilia and NETopathy as key pathologic drivers of progressive lung impairment in patients with COVID-19|https://www.frontiersin.org/articles/10.3389/fphar.2020.00870/full]''’.  Severely ill patients experience acute respiratory distress with high levels of neutrophils and multiple cytokines causing an exaggerated inflammatory response. In this review, the authors discuss the need to develop therapies that inhibit neutrophil recruitment, activation, degranulation, and neutrophil extracellular trap (NET) release. [Read more|https://www.frontiersin.org/articles/10.3389/fphar.2020.00870/full].
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The [COVID Human Genetic Effort|https://www.covidhge.com] is an international consortium of scientists around the world aiming to discover genetic differences between young patients with no underlying medical conditions that develop severe COVID-19 and patients that remain resistant even after repeated exposure to SARS-CoV2. [Guiseppe Novelli|Member/Novelli_Giuseppe] MAE is part of the consortium and co-author of the paper ‘Inborn errors of type I IFN immunity in patients with life-threatening COVID-19’. The paper was published in the journal [Science|https://www.sciencemag.org]. 
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[Guiseppe Novelli|Member/Novelli_Giuseppe] MAE in collaboration with Emilio Di Maria, Andrea Latini and Paola Borgiani carried out a systematic review titled ‘Genetic variants of the human host influencing the coronavirus-associated phenotypes (SARS, MERS and COVID-19): rapid systematic review and field synopsis’. This is the first comprehensive review exploring the current knowledge of the wide spectrum of phenotypes associated SARS-CoV2 infection going from absence of symptoms to severe systemic complications. [Read more|https://humgenomics.biomedcentral.com/articles/10.1186/s40246-020-00280-6].
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[Guiseppe Novelli|Member/Novelli_Giuseppe] MAE led a pilot study in a cohort of 131 Italian patients with the aim to determine if genetic variations on the AC2 receptor, the cellular receptor that binds SARS-CoV-2 spike (S) protein, could explain differences in the susceptibility and severity of infection in COVID-19 clinical cases. The results of this study were published in the paper titled ‘Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients’. [Read more|https://humgenomics.biomedcentral.com/articles/10.1186/s40246-020-00279-z].
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[Guiseppe Novelli|Member/Novelli_Giuseppe] MAE in collaboration with others published a paper titled ‘COVID-19 and genetic variants of proteins involved in the SARS-CoV-2 entry into the host cells’. In this study the authors analysed a cohort of 131 Italian patients looking for variations in the genes coding for other proteins involved in the SARS-CoV-2 infecting human cells. [Read more|https://www.mdpi.com/2073-4425/11/9/1010].
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[Guiseppe Novelli|Member/Novelli_Giuseppe] MAE and others published a paper titled ‘COVID-19 update: the first 6 months of the pandemic’. This review offers a useful summary of strategies for dealing with the COVID-19 pandemic in democratic countries. It includes information on the virus, how it affects humans, the routes of transmission and therapies for the disease. This pandemic playbook is a useful resource in the current pandemic and will be useful in the future when another pandemic might arise. [Read more|https://humgenomics.biomedcentral.com/articles/10.1186/s40246-020-00298-w].
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[Guiseppe Novelli|Member/Novelli_Giuseppe] MAE is part of the [COVID Human Genetic Effort|https://www.covidhge.com] and co-author of the paper ‘Life-threatening COVID-19: defective interferonsunleash excessive inflammation’. This paper discusses how severe COVID-19 pneumonia increases sharply after 65 years of age and how genetic defects as well as autoantibodies against type I interferons contribute to disease severity in at least 10% of critical cases. [Read more|https://www.cell.com/med/fulltext/S2666-6340(20)30029-5#secsectitle0080].
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[Valerie O’Donnell|Member/O'Donnell_Valerie] MAE, in collaboration with others, published an evidence review titled ‘Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection’. This review examines published research on enveloped viruses including coronaviruses, showing that chemicals found in mouthwashes can damage the lipid membrane of enveloped viruses. The authors assessed existing mouthwash formulations for their potential ability to damage the SARS-CoV-2 lipid envelope ''in vitro''. The evidence suggests the use of mouthwash could be an effective defence against COVID-19 and further research in this area is needed. This review was the first paper published by the journal [FUNCTION|https://academic.oup.com/function/issue/1/1]. [Read more|https://academic.oup.com/function/article/1/1/zqaa002/5836301]
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[Ole Petersen|Member/Petersen_Ole] MAE describes, in a [peer-reviewed article|https://academic.oup.com/function/article/1/1/zqaa003/5851680] published in [FUNCTION|https://academic.oup.com/function], an entirely unexpected link between SARS-COV-2 infection and physiological calcium signalling, thereby providing new insights into the mechanism by which this virus enters the cells in our body. [Read more|Acad_Main/News_Archive/Endocytic Uptake of SARS-COV-2].
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[Bernard Rossier|Member/Rossier_Bernard] MAE and Martina Gentzsch published a paper titled ‘A pathophysiological model for COVID-19: Critical importance of transepithelial sodium transport upon airway infection’. The authors propose a mechanism that could explain how SARS-CoV-2 enters the airways during the early stages of infection and the possible role of epithelial sodium channels (ENaC) in the process. This opinion paper was published in the journal FUNCTION.
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[Luca Steardo|Member/Steardo_Luca] MAE, [Robert Zorec|Member/Zorec_Robert] MAE and [Alex Verkhratsky|Member/Verkhratsky_Alexei] MAE, have published a commentary entitled ‘Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19’. [Read more|https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.13473].
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In a review titled ‘[Psychiatric face of COVID-19|Acad_Main/News_Archive/Psychiatric face of COVID-19]’ by Luca Steardo Jr, [Luca Steardo|Member/Steardo_Luca] MAE and [Alex Verkhratsky|Member/Verkhratsky_Alexei] MAE, the authors discuss the serious clinical challenges posed by COVID-19 systemic inflammation that can affect the central nervous system and aggravate mental health disorders. [Read more|https://www.nature.com/articles/s41398-020-00949-5].
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[Alex Verkhratsky|Member/Verkhratsky_Alexei] MAE and others published a review titled ‘Neuropathobiology of COVID-19: The Role for Glia’. The authors discuss the ability of SARS-CoV-2 to enter cells of the central nervous system causing severe neurological inflammation that can result in deficient immune responses and autoimmunity. The consequences of SARS-CoV-2 infection during ageing and pregnancy are also discussed. [Read more|https://www.frontiersin.org/articles/10.3389/fncel.2020.592214/full].
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[Alex Verkhratsky|Member/Verkhratsky_Alexei] MAE, [Gerry Melino|Member/Melino_Gerry] MAE, [Yufang Shi|Member/Shi_Yufang] MAE and others published a paper titled ‘Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?’.  In this review the authors discuss how SARS-CoV-2 directly infects brain cells, causing severe systemic inflammation. Clinical neurological symptoms include dizziness, disturbed sleep, cognitive deficit, hallucinations and depression. COVID-19 damage to neural cells may increase the risk of neurodegenerative diseases like dementia. [Read more|https://biologydirect.biomedcentral.com/articles/10.1186/s13062-020-00282-3].
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