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2.
Euro Surveill ; 25(28)2020 07.
Article in English | MEDLINE | ID: covidwho-647504

ABSTRACT

BackgroundA novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.AimThe cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.MethodsThe SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.ResultsAn immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.ConclusionThe cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Sequence , Animals , Betacoronavirus/genetics , Blotting, Western , COS Cells , Chlorocebus aethiops , Conserved Sequence , Coronavirus Infections/genetics , Coronavirus Infections/virology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay/methods , Fluorescent Antibody Technique/methods , Genome, Viral , Mice , Pandemics , Peptidyl-Dipeptidase A/immunology , Plasmids , Pneumonia, Viral/genetics , Recombinant Proteins/immunology , SARS Virus/genetics , Sequence Alignment , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/genetics , Transfection , Vero Cells , Virus Integration
3.
Euro Surveill ; 25(28)2020 Jul.
Article in English | MEDLINE | ID: covidwho-647502

ABSTRACT

Serological reactivity was analysed in plasma from 436 individuals with a history of disease compatible with COVID-19, including 256 who had been laboratory-confirmed with SARS-CoV-2 infection. Over 99% of laboratory-confirmed cases developed a measurable antibody response (254/256) and 88% harboured neutralising antibodies (226/256). Antibody levels declined over 3 months following diagnosis, emphasising the importance of the timing of convalescent plasma collections. Binding antibody measurements can inform selection of convalescent plasma donors with high neutralising antibody levels.


Subject(s)
Antibodies, Neutralizing/blood , Betacoronavirus/immunology , Coronavirus Infections/blood , Coronavirus Infections/therapy , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Adolescent , Adult , Aged , Antibodies, Neutralizing/therapeutic use , Antibody Specificity , Blood Donors/statistics & numerical data , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , England , Humans , Immunization, Passive/statistics & numerical data , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Statistics, Nonparametric , Time Factors , Young Adult
4.
Euro Surveill ; 25(28)2020 07.
Article in English | MEDLINE | ID: covidwho-647501

ABSTRACT

Most cases of coronavirus disease 2019 are mild or asymptomatic. Therefore, many cases remain unrecorded. We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. The IgG seroprevalence was 0.91% (95% confidence interval (CI): 0.58-1.24) overall, ranging from 0.66% (95% CI: 0.13-1.19) in Hesse to 1.22% (95% CI: 0.33-2.10) in Lower-Saxony.


Subject(s)
Betacoronavirus/immunology , Blood Donors/statistics & numerical data , Coronavirus Infections/immunology , Immunoglobulin G/blood , Pneumonia, Viral/immunology , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Germany/epidemiology , Humans , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology , Time Factors
5.
Int J Environ Res Public Health ; 17(11)2020 06 10.
Article in English | MEDLINE | ID: covidwho-622436

ABSTRACT

The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such as STAT3 (signal transducer and activator of transcription 3), IKK (IκB kinase), MMP9 (matrix metallopeptidase 9), MAPK (mitogen-activated protein kinases), COX2 (cyclooxigenase 2), and NF-Kß (nuclear factor kappa-light-chain-enhancer of activated B cells). Multiple intervention studies have demonstrated that lifestyle changes can lead to reduced inflammation and improved health. This can be linked to the concept of real-life risk simulation, since humans are continuously exposed to dietary factors in small doses and complex combinations (e.g., polyphenols, fibers, polyunsaturated fatty acids, etc.). Inflammation biomarkers improve in patients who consume a certain amount of fiber per day; some even losing weight. Fasting in combination with calorie restriction modulates molecular mechanisms such as m-TOR, FOXO, NRF2, AMPK, and sirtuins, ultimately leads to significantly reduced inflammatory marker levels, as well as improved metabolic markers. Moving toward healthier dietary habits at the individual level and in publicly-funded institutions, such as schools or hospitals, could help improving public health, reducing healthcare costs and improving community resilience to epidemics (such as COVID-19), which predominantly affects individuals with metabolic diseases.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Diet , Inflammation/immunology , Metabolic Diseases/immunology , Pneumonia, Viral/immunology , Risk Reduction Behavior , Coronavirus Infections/diet therapy , Coronavirus Infections/prevention & control , Humans , Inflammation/diet therapy , Inflammation/prevention & control , Metabolic Diseases/diet therapy , Metabolic Diseases/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/diet therapy , Pneumonia, Viral/prevention & control , Primary Prevention
6.
Cell Metab ; 32(1): 31-43, 2020 07 07.
Article in English | MEDLINE | ID: covidwho-635840

ABSTRACT

For centuries, people believed that bats possessed sinister powers. Bats are thought to be ancestral hosts to many deadly viruses affecting humans including Ebola, rabies, and most recently SARS-CoV-2 coronavirus. However, bats themselves tolerate these viruses without ill effects. The second power that bats have is their longevity. Bats live much longer than similar-sized land mammals. Here we review how bats' ability to control inflammation may be contributing to their longevity. The underlying mechanisms may hold clues to developing new treatments for age-related diseases. Now may be the time to use science to exploit the secret powers of bats for human benefit.


Subject(s)
Aging/physiology , Betacoronavirus/immunology , Chiroptera/physiology , Longevity/physiology , Aging/immunology , Animals , Chiroptera/immunology , Chiroptera/virology , Coronavirus Infections/immunology , Humans , Inflammation/immunology , Pandemics , Pneumonia, Viral/immunology , Telomere Homeostasis/genetics
7.
Rheumatol Int ; 40(9): 1353-1360, 2020 09.
Article in English | MEDLINE | ID: covidwho-640396

ABSTRACT

As of June 10th 2020 about 7.2 million individuals have tested positive for, and more than 410,000 have died due to COVID-19. In this review we outline the pathophysiology that underpins the potential use of anti-rheumatic therapies for severe COVID-19 infection and summarize the current evidence regarding the risk and outcome of COVID-19 in patients with systemic autoimmune diseases. Thus far there is no convincing evidence that any disease-modifying anti-rheumatic drug (conventional synthetic, biologic or targeted synthetic) including hydroxychloroquine, may protect against severe COVID-19 infection; answers about their possible usefulness in the management of the cytokine storm associated with severe COVID-9 infection will only arise from ongoing randomized controlled trials. Evidence on COVID-19 risk and outcome in patients with systemic autoimmune diseases is extremely limited; thus, any conclusions would be unsafe and should be seen with great caution. At present, the risk and severity (hospitalization, intensive care unit admission and death) of COVID-19 infection in people with autoimmune diseases do not appear particularly dissimilar to the general population, with the possible exception of hospitalization in patients exposed to high glucocorticoid doses. At this stage it is impossible to draw any conclusions for differences in COVID-19 risk and outcome between different autoimmune diseases and between the various immunomodulatory therapies used for them. More research in the field is obviously required, including as a minimum careful and systematic epidemiology and appropriately controlled clinical trials.


Subject(s)
Antirheumatic Agents/therapeutic use , Autoimmune Diseases/drug therapy , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Pneumonia, Viral/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Autoimmune Diseases/epidemiology , Autoimmune Diseases/immunology , Betacoronavirus , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Humans , Janus Kinase Inhibitors/therapeutic use , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Risk Factors , Severity of Illness Index , Tumor Necrosis Factor Inhibitors/therapeutic use
8.
Int J Immunogenet ; 47(4): 319-323, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-640248

ABSTRACT

Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing immunogenetic knowledge of virus-immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/immunology , Immunity, Innate/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/pathology , Disease Susceptibility/immunology , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Pandemics , Pneumonia, Viral/drug therapy , Tumor Necrosis Factor-alpha/metabolism
9.
Int Immunopharmacol ; 86: 106760, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-634138

ABSTRACT

Due to the vastness of the science virology, it is no longer an offshoot solely of the microbiology. Viruses have become as the causative agents of major epidemics throughout history. Many therapeutic strategies have been used for these microorganisms, and in this way the recognizing of potential targets of viruses is of particular importance for success. For decades, antibodies and antibody fragments have occupied a significant body of the treatment approaches against infectious diseases. Because of their high affinity, they can be designed and engineered against a variety of purposes, mainly since antibody fragments such as scFv, nanobody, diabody, and bispecific antibody have emerged owing to their small size and interesting properties. In this review, we have discussed the antibody discovery and molecular and biological design of antibody fragments as inspiring therapeutic and diagnostic agents against viral targets.


Subject(s)
Antibodies, Viral/therapeutic use , Betacoronavirus/immunology , Biological Products/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antibodies, Bispecific/immunology , Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/immunology , Biological Products/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Disease Models, Animal , Drug Design , Drug Discovery , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Single-Domain Antibodies/immunology , Single-Domain Antibodies/therapeutic use
10.
Curr Res Transl Med ; 68(3): 105-110, 2020 08.
Article in English | MEDLINE | ID: covidwho-631298

ABSTRACT

The relative ease of isolation of mesenchymal stem cells (MSCs) from different tissues coupled with their culture expansion in vitro and their differentiation capacity to mesodermal, endodermal and ectodermal lineages have made these cells attractive for a large number of therapeutic applications. In recent years, there has been remarkable progress in the utilization of MSCs in diverse clinical indications both in animal models and human clinical trials. However, the potential of MSCs to control or treat viral diseases is still in its infancy. In this study, we report quantitative data on the MSC-based clinical trials over the last ten years as they appear on the online database of clinical research studies from US National Institutes of Health. In particular, we provide comprehensive review of either completed or ongoing clinical trials using MSCs for virus-associated diseases focusing on HIV, hepatitis B virus and COVID-19 virus.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Virus Diseases/therapy , Virus Physiological Phenomena , Animals , Betacoronavirus/physiology , Cell Culture Techniques , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , HIV/physiology , Hepatitis B virus/physiology , Humans , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Virus Diseases/epidemiology , Virus Diseases/immunology , Viruses/pathogenicity
11.
Virol Sin ; 35(3): 290-304, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-618224

ABSTRACT

The recent outbreak of coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Disease Models, Animal , Middle East Respiratory Syndrome Coronavirus , Pneumonia, Viral/virology , SARS Virus , Severe Acute Respiratory Syndrome/virology , Animals , Betacoronavirus/pathogenicity , Camelids, New World , Camelus , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Mice , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/physiopathology , Severe Acute Respiratory Syndrome/therapy , Swine
14.
Pol Arch Intern Med ; 130(7-8): 662-667, 2020 08 27.
Article in English | MEDLINE | ID: covidwho-761201

ABSTRACT

The intriguing aspects of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) are the high rate of spread and rapid progression of pneumonitis. Confronted with thousands of deaths daily worldwide, we have to quickly build the rationale behind the treatment, taking advantage of past analogues. When a new virus strikes, T­cell receptor γδ cells are in the first line of defense, activated by stress molecules and recognizing some epitopes in a process that is major histocompatibility complex-independent but still specific, eg, cytomegalovirus, as well as participating in the regulatory mechanism-both characteristics are useful in fighting SARS­CoV­2. Most deaths occur due to pneumonitis, in the course of which overwhelming inflammation impairs blood oxygenation, calling for artificial ventilation. In fatal cases of coronavirus disease 2019, the balance between the immune response and the inflammatory outcome fails and, therefore, patients at risk, mostly the elderly, show higher levels of anti-SARS­CoV­2 antibodies and enhanced inflammation in the lungs. Apparently, there is no feedback control over the antibody production. The investigational use of convalescent plasma, providing antibodies taken from patients who have recovered, was shown to be effective, likely through exerting idiotype­associated negative control of antibody production. Similarly, the use of mesenchymal stem cells may assist the body regulatory mechanisms, considering the anti­inflammatory potential of these cells. The use of these 2 immunotherapeutic tools is understandable based on basic immunology and this knowledge may direct the efforts of the medical community aimed at combating the virus.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Receptors, Antigen, T-Cell/immunology , Flow Cytometry , Humans , Immune System , Pandemics
15.
Chiropr Man Therap ; 28(1): 21, 2020 05 04.
Article in English | MEDLINE | ID: covidwho-760596

ABSTRACT

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system.


Subject(s)
Coronavirus Infections/prevention & control , Immunization , Manipulation, Chiropractic , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Chiropractic , Coronavirus Infections/immunology , Humans , Immunization/methods , Pneumonia, Viral/immunology , Societies, Medical
17.
Int J Mol Med ; 46(3): 903-912, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-750592

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is a novel ß coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID­19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID­19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID­19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID­19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of D­dimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARS­CoV­2 infection may represent a secondary anti­phospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID­19 infection. Diagnostic and therapeutic implications of this are also discussed.


Subject(s)
Antiphospholipid Syndrome/pathology , Coronavirus Infections/pathology , Disseminated Intravascular Coagulation/pathology , Pneumonia, Viral/pathology , Thromboembolism/pathology , Thrombosis/pathology , Antiphospholipid Syndrome/immunology , Antiviral Agents/therapeutic use , Betacoronavirus , Blood Coagulation/physiology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Disseminated Intravascular Coagulation/immunology , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Pandemics , Phospholipids/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Thromboembolism/immunology
18.
Blood ; 136(10): 1169-1179, 2020 09 03.
Article in English | MEDLINE | ID: covidwho-748867

ABSTRACT

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support. Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis. We studied the connection between NETs and COVID-19 severity and progression. We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17). We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines. Three COVID-19 lung autopsies were examined for NETs and platelet involvement. We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma. We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma. Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome. Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340). Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration. Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF. Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.


Subject(s)
Coronavirus Infections/complications , Extracellular Traps/immunology , Neutrophils/immunology , Pneumonia, Viral/complications , Thrombosis/complications , Adult , Aged , Betacoronavirus/immunology , Blood Platelets/immunology , Blood Platelets/pathology , Blood Proteins/immunology , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Female , Humans , Male , Middle Aged , Neutrophil Infiltration , Neutrophils/pathology , Pandemics , Peroxidase/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Prospective Studies , Thrombosis/immunology , Thrombosis/pathology
19.
J Am Acad Dermatol ; 83(3): 870-875, 2020 09.
Article in English | MEDLINE | ID: covidwho-747574

ABSTRACT

BACKGROUND: During the coronavirus disease 2019 pandemic, several acral chilblain-like lesions were observed in young patients with suspected, but mostly unconfirmed, infection with severe acute respiratory syndrome coronavirus 2. The histopathologic aspect of these lesions is as yet poorly known. OBJECTIVE: To investigate the pathologic features of chilblain-like lesions. METHODS: Biopsies were obtained from 17 cases of chilblain-like lesions during the coronavirus disease 2019 pandemic in France and were studied by routine histologic examination, immunohistochemistry, and direct immunofluorescence. The patients had suspected but unconfirmed infection with severe acute respiratory syndrome coronavirus 2 (negative nasopharyngeal polymerase chain reaction and serologic test results). RESULTS: Chilblain-like lesions showed many features in common with those reported in idiopathic and autoimmune-related chilblains, including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4+) inflammation, and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, and immunoreactant deposits on vessels). CONCLUSIONS: Chilblain-like lesions show histopathologic features similar to those of idiopathic and autoimmune-related chilblains, with a high rate of vascular changes and direct immunofluorescence positivity. The role of severe acute respiratory syndrome coronavirus 2 in the development of these puzzling lesions remains to be elucidated.


Subject(s)
Betacoronavirus/isolation & purification , Chilblains/diagnosis , Coronavirus Infections/complications , Pneumonia, Viral/complications , Skin Diseases/diagnosis , Skin/pathology , Adolescent , Adult , Betacoronavirus/immunology , Biopsy , Chilblains/immunology , Chilblains/pathology , Chilblains/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Diagnosis, Differential , Female , Fluorescent Antibody Technique , France , Humans , Immunohistochemistry , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Skin/immunology , Skin/virology , Skin Diseases/immunology , Skin Diseases/pathology , Skin Diseases/virology , Toes , Young Adult
20.
Trials ; 21(1): 766, 2020 Sep 05.
Article in English | MEDLINE | ID: covidwho-745676

ABSTRACT

OBJECTIVES: To investigate the potential efficacy of Acacia Senegal extract Gum Arabic (GA) supplementation as immunomodulatory and anti-inflammatory dietary intervention among newly diagnosed COVID 19 Sudanese patients. To study the effect of GA on the level of cytokines, TNFα, IL8, IL6 IL10, CRP and the viral load. Secondary outcomes will be the effect of GA oral intake on mortality rate and days of hospital admission. TRIAL DESIGN: Quadruple blind, randomized placebo-controlled clinical trial Phase II & III. Prospective, two-arm, parallel-group, randomised (1:1 allocation ratio) superiority trial of oral GA among seropositive COVID-19 patients. PARTICIPANTS: Inclusion criteria: COVID-19 infected (newly diagnosed) as proved by real-time PCR within 72 hours of PCR. Age 8-90 years Both genders Exclusion criteria: Intubated patients on parenteral treatment Allergy to Gum Arabic The study will be conducted in COVID Isolation Centres and Soba University Hospital Khartoum State Sudan. INTERVENTION AND COMPARATOR: Experimental: Intervention Group This arm will receive 100% natural Gum Arabic provided in a powder form in 30-grams-dose once daily for four weeks Placebo Comparator: Control group: This group will be provided with pectin powder provided as one-gram-dose once daily for four weeks Both GA and placebo will be in addition to standard care treatment based on local clinical guidelines. MAIN OUTCOMES: Mean change from baseline score of Immune Response to end of the trial. Changes of the level of Tumor Necrosis Factor (TNFα), interleukin IL8, IL6, and IL10 from the baseline values (Four weeks from the start of randomization). Mortality rate: The percentage of deaths among COVID 19 patients received Gum Arabic compared to placebo (Four weeks from the start of randomization]). RANDOMISATION: Randomization (1:1 allocation ratio) and will be conducted using a sequence of computer-generated random numbers by an independent individual. Each participating centre will be assigned a special code generated by the computer. The randomization will be kept by the PI and a research assistant. BLINDING (MASKING): Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 110 eligible patients will be randomly assigned to either GA (n=55) or placebo (n=55) groups. TRIAL STATUS: Protocol Version no 2, 30th June 2020. Recruitment will start on 15th September 2020. The intended completion date is 15th January 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04381871 . Date of trial registration: 11 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Gum Arabic/therapeutic use , Immunologic Factors/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Child , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Gum Arabic/adverse effects , Host Microbial Interactions , Humans , Immunologic Factors/adverse effects , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Prospective Studies , Randomized Controlled Trials as Topic , Time Factors , Treatment Outcome , Young Adult
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