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1.
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
2.
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
3.
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
4.
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
5.
Viruses ; 12(7)2020 07 07.
Article in English | MEDLINE | ID: covidwho-639283

ABSTRACT

Standard precautions to minimize the risk of SARS-CoV-2 transmission implies that infected cell cultures and clinical specimens may undergo some sort of inactivation to reduce or abolish infectivity. We evaluated three heat inactivation protocols (56 °C-30 min, 60 °C-60 min and 92 °C-15 min) on SARS-CoV-2 using (i) infected cell culture supernatant, (ii) virus-spiked human sera (iii) and nasopharyngeal samples according to the recommendations of the European norm NF EN 14476-A2. Regardless of the protocol and the type of samples, a 4 Log10 TCID50 reduction was observed. However, samples containing viral loads > 6 Log10 TCID50 were still infectious after 56 °C-30 min and 60 °C-60 min, although infectivity was < 10 TCID50. The protocols 56 °C-30 min and 60 °C-60 min had little influence on the RNA copies detection, whereas 92 °C-15 min drastically reduced the limit of detection, which suggests that this protocol should be avoided for inactivation ahead of molecular diagnostics. Lastly, 56 °C-30 min treatment of serum specimens had a negligible influence on the results of IgG detection using a commercial ELISA test, whereas a drastic decrease in neutralizing titers was observed.


Subject(s)
Betacoronavirus , Containment of Biohazards/methods , Coronavirus Infections/virology , Pneumonia, Viral/virology , Serologic Tests/methods , Virus Inactivation , Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Containment of Biohazards/standards , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Enzyme-Linked Immunosorbent Assay , Hot Temperature , Humans , Neutralization Tests , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Serologic Tests/standards
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.
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
8.
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
9.
Trials ; 21(1): 499, 2020 06 08.
Article in English | MEDLINE | ID: covidwho-768581

ABSTRACT

OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. TRIAL DESIGN: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. PARTICIPANTS: Eligible participants include adults (≥ 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for ≥ 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. INTERVENTION AND COMPARATOR: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 - 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 - 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. MAIN OUTCOMES: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. RANDOMIZATION: Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. BLINDING (MASKING): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. TRIAL STATUS: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of 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/immunology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Randomized Controlled Trials as Topic , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Clinical Trials, Phase II as Topic , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods , Pandemics , Prospective Studies
10.
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
11.
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
12.
J Virol ; 94(17)2020 08 17.
Article in English | MEDLINE | ID: covidwho-748774

ABSTRACT

In this review, we address issues that relate to the rapid "Warp Speed" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of humans and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans and discuss the outcome and interpretation of virus challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which were not included in the initial wave of Warp Speed immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV) vaccines. We conclude by outlining the possible outcomes of the Warp Speed vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine/immunology , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing , Antibodies, Viral/immunology , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Models, Animal , Pandemics/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/adverse effects
13.
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
14.
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
15.
MMWR Morb Mortal Wkly Rep ; 69(35): 1221-1226, 2020 Sep 04.
Article in English | MEDLINE | ID: covidwho-745360

ABSTRACT

Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Personnel, Hospital/statistics & numerical data , Pneumonia, Viral/epidemiology , Academic Medical Centers , Adult , Asymptomatic Diseases , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Cross Infection/prevention & control , Female , Humans , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Male , Middle Aged , Pandemics/prevention & control , Personal Protective Equipment/statistics & numerical data , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Seroepidemiologic Studies , United States/epidemiology
18.
S Afr Med J ; 110(9): 842-845, 2020 07 17.
Article in English | MEDLINE | ID: covidwho-743542

ABSTRACT

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections , Immunologic Tests/methods , Pandemics , Pneumonia, Viral , Serologic Tests/methods , Betacoronavirus/genetics , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/standards , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Reproducibility of Results , Sensitivity and Specificity , Seroepidemiologic Studies , South Africa/epidemiology
19.
Int J Mol Sci ; 21(17)2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-742800

ABSTRACT

When facing an acute viral infection, our immune systems need to function with finite precision to enable the elimination of the pathogen, whilst protecting our bodies from immune-related damage. In many instances however this "perfect balance" is not achieved, factors such as ageing, cancer, autoimmunity and cardiovascular disease all skew the immune response which is then further distorted by viral infection. In SARS-CoV-2, although the vast majority of COVID-19 cases are mild, as of 24 August 2020, over 800,000 people have died, many from the severe inflammatory cytokine release resulting in extreme clinical manifestations such as acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH). Severe complications are more common in elderly patients and patients with cardiovascular diseases. Natural killer (NK) cells play a critical role in modulating the immune response and in both of these patient groups, NK cell effector functions are blunted. Preliminary studies in COVID-19 patients with severe disease suggests a reduction in NK cell number and function, resulting in decreased clearance of infected and activated cells, and unchecked elevation of tissue-damaging inflammation markers. SARS-CoV-2 infection skews the immune response towards an overwhelmingly inflammatory phenotype. Restoration of NK cell effector functions has the potential to correct the delicate immune balance required to effectively overcome SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Disease Susceptibility/immunology , Host-Pathogen Interactions/immunology , Immunity, Innate , Killer Cells, Natural/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Autoimmunity , Coronavirus Infections/metabolism , Humans , Immunomodulation , Killer Cells, Natural/metabolism , Pandemics , Pneumonia, Viral/metabolism
20.
Sci Rep ; 10(1): 14179, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-741695

ABSTRACT

A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.


Subject(s)
Betacoronavirus/immunology , Computational Biology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Host-Pathogen Interactions/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Viral Proteins/immunology , Amino Acid Sequence , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/metabolism , Computational Biology/methods , Coronavirus Infections/metabolism , Epitopes, B-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/chemistry , Genome, Viral , Genomics/methods , Humans , Models, Molecular , Pandemics , Peptides/chemistry , Peptides/immunology , Phylogeny , Pneumonia, Viral/metabolism , Structure-Activity Relationship , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccines, Subunit/immunology , Viral Proteins/chemistry , Viral Vaccines/immunology
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