scholarly journals Immunologic aspect in diagnosis and treatment of SARS-COV-2 patients

2020 ◽  
Vol 3 (2) ◽  
pp. 113-121
Author(s):  
Sumaiya Yasin ◽  
Theophilus Bhatti ◽  
Muhammad Umer Farooqi ◽  
Farrukh Mateen
Keyword(s):  
Therapeutic Option ◽  
Lung Epithelial Cells ◽  
Confirmatory Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nasopharyngeal Swab ◽  
Angiotensin Converting Enzyme 2 ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Available Information ◽  
Respiratory Droplets

Recent worldwide outbreak of novel coronavirus disease (CoVID-19) has affected massive human population including Pakistan, and has caused a huge number of mortalities in few months. CoVID-19 is an infectious disease caused by a virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which is single stranded RNA enveloped beta coronavirus and affects lower respiratory tract. It transmits from human to human through respiratory droplets. It uses its S-protein to recognize ACE2 (Angiotensin Converting Enzyme-2) receptors in lung epithelial cells where it attaches and causes infection. The incubation period is 2-14 days. In pre-symptomatic phase, body’s immune system starts antibodies production. Significant antibodies are IgM and IgG that produces within 03-06 days and 8-12 days respectively. This review provides the available information about immunological aspects in terms of diagnosis and screening of CoVID-19 and potential therapeutic targets for combating SARS-CoV-2 infection. Immunologic techniques to detect these antibodies are ELISA (Enzyme-linked Immunosorbent Assay), CMIA (Chemiluminescent Micro particle Immunoassay) and ICT (Immunochromatographic Test). Among these, ELISA and CMIA are found to be highly specific and sensitive in convalescent phase of infection. While the fundamental confirmatory test for SARS-CoV-2 infection is RT-PCR (Reverse Transcription Polymerase Chain Reaction) which detects the viral RNA in respiratory samples preferably nasopharyngeal swab. Serological assays are essential to find out rate of infection, and most importantly antibody titers in recovered patients to be used for therapeutic purpose. After some successful studies Convalescent Plasma is considered as a good therapeutic option in the absence of specific antiviral therapy.

Current Insights into the Novel Coronavirus Disease 2019 (COVID-19) and Its Homoeopathic Management

2020 ◽  
Vol 33 (03) ◽  
pp. 171-179
Author(s):  
Sanjay Kumar Dey ◽  
Joy Kumar Dey ◽  
Hitaishi Sihag
Keyword(s):  
Close Contact ◽  
Infected Individual ◽  
Case Fatality ◽  
The Novel ◽  
Plasma Therapy ◽  
Angiotensin Converting Enzyme 2 ◽  
Clinical Research Trials ◽  
Novel Coronavirus ◽  
Respiratory Droplets ◽  
Gelsemium Sempervirens

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus strain that has not been ever found in humans before December 2019. Both the coronavirus disease 2019 (COVID-19) case fatality rate and deaths per million population in the top 10 affected countries are increasing a lot due to ever-increasing number of new cases among countries facilitated by increased affinity of SARS-CoV-2 to bind human angiotensin-converting enzyme 2 (ACE2) receptors. While human-to-human transmission of SARS-CoV-2 happens through close contact with an infected individual who spreads respiratory droplets through air or other means, its diagnosis relies mainly on detection of nucleic acid. Repurposing drugs such as dexamethasone, remdesivir, favipiravir and TMPRSS2 (trans membrane protease, serine 2) protease inhibitors have been shown to be effective for the treatment of COVID-19 with albeit requirement of further studies to conclude their complete effectiveness. Personal protective measures should be followed to prevent SARS-CoV-2 infection. Additionally, hundreds of clinical trials of vaccines against SARS-CoV-2 are undergoing, while plasma therapy from the COVID-19 survivors is also being tried to treat the severely affected patients. In addition to these aforementioned modern medicines and therapeutic approaches, homoeopathy also holds promising anti-viral effect as evident from its success against flu and other epidemics, historically. Therefore, present article provides a glimpse of advancements made in the area of homoeopathic ways of treating COVID-19 by summarising the recent homoeopathic clinical, research trials and future scopes of homoeopathy to combat the pandemic. After critical review of most of the ongoing or recently completed homoeopathic treatment efforts against SARS-CoV-2, it was identified that Bryonia alba, Arsenicum album and Gelsemium sempervirens are working best among homoeopathic medicines till now. These studies are also suggesting an increased application of these remedies to treat the current pandemic worldwide; therefore, more such studies are warranted. Those further research will pave the way to understand the mechanism of each of these homoeopathic drugs to cure COVID-19 facilitated by optimising their doses, effects and find the best among these multiple options in homoeopathic medicines for plausible mono- or combination therapies.

scholarly journals Predicting the Efficacy of COVID-19 Convalescent Plasma Donor Units with the Lumit Dx anti-Receptor Binding Domain Assay

2021 ◽  
Author(s):  
Sanath Kumar Janaka ◽  
Natasha M Clark ◽  
David T Evans ◽  
Joseph P Connor
Keyword(s):  
Receptor Binding ◽  
Therapeutic Option ◽  
Passive Immunization ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Antibody Assays ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Design And Methods

AbstractBackgroundThe novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier.Study design and methodsSince virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx).ResultsAll measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays.DiscussionOur observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.

scholarly journals The COVID-19 pandemic: a global health crisis

2020 ◽  
Vol 52 (11) ◽  
pp. 549-557
Author(s):  
Casey A. Pollard ◽  
Michael P. Morran ◽  
Andrea L. Nestor-Kalinoski
Keyword(s):  
Pulmonary Fibrosis ◽  
Geographic Location ◽  
The United States ◽  
Viral Envelope ◽  
Lung Epithelial Cells ◽  
World Health ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Health Organization

The novel coronavirus SARS-CoV-2 was identified as the causative agent for a series of atypical respiratory diseases in the Hubei Province of Wuhan, China in December of 2019. The disease SARS-CoV-2, termed COVID-19, was officially declared a pandemic by the World Health Organization on March 11, 2020. SARS-CoV-2 contains a single-stranded, positive-sense RNA genome surrounded by an extracellular membrane containing a series of spike glycoproteins resembling a crown. COVID-19 infection results in diverse symptoms and morbidity depending on individual genetics, ethnicity, age, and geographic location. In severe cases, COVID-19 pathophysiology includes destruction of lung epithelial cells, thrombosis, hypercoagulation, and vascular leak leading to sepsis. These events lead to acute respiratory distress syndrome (ARDS) and subsequent pulmonary fibrosis in patients. COVID-19 risk factors include cardiovascular disease, hypertension, and diabetes, which are highly prevalent in the United States. This population has upregulation of the angiotensin converting enzyme-2 (ACE2) receptor, which is exploited by COVID-19 as the route of entry and infection. Viral envelope proteins bind to and degrade ACE2 receptors, thus preventing normal ACE2 function. COVID-19 infection causes imbalances in ACE2 and induces an inflammatory immune response, known as a cytokine storm, both of which amplify comorbidities within the host. Herein, we discuss the genetics, pathogenesis, and possible therapeutics of COVID-19 infection along with secondary complications associated with disease progression, including ARDS and pulmonary fibrosis. Understanding the mechanisms of COVID-19 infection will allow the development of vaccines or other novel therapeutic approaches to prevent transmission or reduce the severity of infection.

scholarly journals SARS-CoV-2 Assays To Detect Functional Antibody Responses That Block ACE2 Recognition in Vaccinated Animals and Infected Patients

2020 ◽  
Vol 58 (11) ◽  
Author(s):  
Susanne N. Walker ◽  
Neethu Chokkalingam ◽  
Emma L. Reuschel ◽  
Mansi Purwar ◽  
Ziyang Xu ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
The United States ◽  
Spike Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Single Experiment ◽  
Severe Respiratory Distress ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Significant Mortality

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and nonhuman primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor blocking of sera from SARS-CoV-2-infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and assess the efficacy of vaccines.

scholarly journals LB-15. A Trans-Governmental Collaborative Effort to Independently Evaluate SARS-CoV-2 Serology Assays Using Well-Characterized Sample Panels

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S851-S851
Author(s):  
Ribhi Shawar ◽  
Brendan O’Leary ◽  
Troy Kemp ◽  
James Cherry ◽  
S Michele Owen ◽  
...  
Keyword(s):  
Positive Result ◽  
National Laboratory ◽  
Nucleic Acid Amplification ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Samples ◽  
Serum Samples ◽  
Antibody Titers ◽  
Antibody Class ◽  
Novel Coronavirus ◽  
Regulatory Decisions

Abstract Background The emergence of the novel coronavirus, SARS-CoV-2, created a crucial need for accurate tests for diagnosis, assessment of prior infection, and understanding its natural history. Serology assays play an important role in the assessment of anti-viral immune responses and previous infections. Evaluation of serology assays with well-characterized serum and/or plasma samples is critical to determine assay performance. CDC, FDA and NCI’s Frederick National Laboratory for Cancer Research (NCI-FNLCR) have established a collaborative network to independently evaluate commercial antibody tests prior to their authorization. Methods Positive (n=30) serum samples with a range of anti-SARS-CoV-2 antibody titers (Table) and negative (n=80) serum and/or plasma samples were selected to establish performance evaluation panels (PEVs). Three PEVs with similar overall antibody titer distribution have been created. Negative samples were collected prior to 2020, before the SARS-CoV-2 pandemic. Positive samples were from patients previously confirmed to have SARS-CoV-2 using a nucleic acid amplification test. Each sample was characterized at CDC and NCI-FNLCR for presence/absence of SARS-CoV-2 IgM and IgG antibodies using a SARS-CoV-2 spike enzyme linked immunosorbent assay (ELISA). NCI-FNLCR also performed a SARS-CoV-2 spike Receptor Binding Domain (RBD) IgG ELISA. Positive samples were assessed at multiple dilutions. Manufacturers submitted their serology assays for evaluation by this program. The sensitivity of each test was assessed for each antibody class (IgG and IgM) and in a combined manner, where a positive result for either antibody was considered as a positive result. For combined specificity, a negative result meant a sample was negative for both antibodies (IgG and IgM). Number of positive samples with anti-SARS-CoV-2 spike antibodies for each panel (n=30) Results To date, 53 serology assays have been evaluated. Sensitivity ranged from 30.0% to 100% for IgG, from 10.0% to 100% for IgM, and the combined specificity ranged from 57.5% to 100%. For 2 assays that measure total Ig, sensitivity was 96.7% and 100%. Conclusion This program completed over 50 performance evaluations with well-characterized PEVs. Results have been used to inform FDA regulatory decisions and are publicly available on FDA’s website. Disclosures Cristina Cassetti, PhD, Nothing to disclose

scholarly journals Predicting the efficacy of COVID-19 convalescent plasma donor units with the Lumit Dx anti-receptor binding domain assay

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253551
Author(s):  
Sanath Kumar Janaka ◽  
Natasha M. Clark ◽  
David T. Evans ◽  
Huihui Mou ◽  
Michael Farzan ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Therapeutic Option ◽  
Passive Immunization ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Antibody Assays ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Design And Methods

Background The novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier. Study design and methods Since virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx). Results All measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays. Discussion Our observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.

scholarly journals Lead SARS-CoV-2 Candidate Vaccines: Expectations from Phase III Trials and Recommendations Post-Vaccine Approval

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 54
Author(s):  
Ebenezer Tumban
Keyword(s):  
Phase I ◽  
Geometric Mean ◽  
Spike Protein ◽  
Phase Iii ◽  
The European Union ◽  
Angiotensin Converting Enzyme 2 ◽  
The United Kingdom ◽  
Phase Iii Trials ◽  
Antibody Titers ◽  
Respiratory Droplets

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through respiratory droplets/aerosols and it causes COVID-19. The virus infects epithelial cells by using the spike protein on its surface to bind to angiotensin-converting enzyme 2 receptor on the cells. Thus, candidate vaccines targeting the spike protein are currently being developed to prevent against infections. Approximately 44 SARS-CoV-2 candidate vaccines are in clinical trials (phase I–III) and an additional 164 candidates are in preclinical stages. The efficacy data from phase I/II trials of lead candidate vaccines look very promising with virus-neutralizing geometric mean antibody titers in the range of 16.6–3906. Most recently, two SARS-CoV-2 candidate vaccines, BNT162b2 and mRNA-1273, have been granted the first emergency use authorization (EUA) in the U.S.; BNT162b2 has also been granted an EUA in the United Kingdom, Canada, and in the European Union. This review assesses whether SARS-CoV-2 candidate vaccines (with approved EUA or in phase III trials) meet the criteria for an ideal SARS-CoV-2 vaccine. The review concludes with expectations from phase III trials and recommendations for phase IV studies (post-vaccine approval).

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

Can Mandated BCG Vaccine Promote herd Immunity against Novel Coronavirus? A Potential Solution at Hand to Tackle Covid-19 Pandemic

2020 ◽  
Vol 16 (1) ◽  
pp. 6-11
Author(s):  
Ashok Arasu ◽  
Pavithra Balakrishnan ◽  
Thirunavukkarasu Velusamy ◽  
Thiagarajan Ramesh
Keyword(s):  
Protective Factor ◽  
Herd Immunity ◽  
Bcg Vaccine ◽  
Intestinal Cells ◽  
Global Public Health ◽  
Wuhan City ◽  
Live Attenuated Vaccine ◽  
Angiotensin Converting Enzyme 2 ◽  
Lung Epithelial ◽  
Novel Coronavirus

The 2019 novel coronavirus (2019-nCoV) infection is an emerging pandemic that poses a severe threat to global public health. This pandemic started from the Wuhan City of Hubei Province in China, and is speculated to have originated from bats and spread among humans with an unknown intermediate transmitter. The virus binds to angiotensin-converting enzyme 2 (ACE2), which is abundantly expressed on various human cells, including lung epithelial and intestinal cells, thereby entering into these cells and causing infection. It is transmitted to other humans through airborne droplets from infected patients. Presently there are no specific treatments or vaccines that are available to curtail the spread of this disease. There are few indirect reports that explain the potential importance of the mandated BCG vaccine as a protective factor against COVID-19. There is a speculation that a live attenuated vaccine (BCG vaccine) can be beneficial against COVID-19 to develop the initial immune response, and can also spread in the community, thereby boosting herd immunity to fight against COVID-19. This review summarizes the conclusions of various reports on the BCG vaccine, and is an attempt to establish BCG-vaccination mediated herd immunity as an effective instant intermediate approach in curbing COVID-19 spread in highly populous countries.

Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Vol 20 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

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