Evaluation of antibody response in symptomatic and asymptomatic covid-19 patients and diagnostic assessment of new IgM/IgG elisa kits

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This study aims to study the immune response and evaluate the performances of four new IgM and five IgG enzyme-linked immunosorbent assay (ELISA) kits for detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies against different antigens in symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) patients. A total of 291 samples collected from symptomatic and asymptomatic RT–PCR-confirmed patients were used to evaluate the ELISA kits’ performance (EDI, AnshLabs, DiaPro, NovaLisa, and Lionex). The sensitivity was measured at three different time-intervals post symptoms onset or positive SARS-CoV-2 RT–PCR test (≤14, 14–30, >30 days). The specificity was investigated using 119 pre-pandemic serum samples. The sensitivity of all IgM kits gradually decreased with time, ranging from 48.7% (EDI)–66.4% (Lionex) at ≤14 days, 29.1% (NovaLisa)–61.8% (Lionex) at 14–30 days, and 6.0% (AnshLabs)–47.9% (Lionex) at >30 days. The sensitivity of IgG kits increased with time, peaking in the latest interval (>30 days) at 96.6% (Lionex). Specificity of IgM ranged from 88.2% (Lionex)–99.2% (EDI), while IgG ranged from 75.6% (DiaPro)–98.3% (Lionex). Among all RT–PCR-positive patients, 23 samples (7.9%) were seronegative by all IgG kits, of which only seven samples (30.4%) had detectable IgM antibodies. IgM assays have variable and low sensitivity, thus considered a poor marker for COVID-19 diagnosis. IgG assays can miss at least 8% of RT–PCR-positive cases

COVID-19 Vaccine Platforms: Challenges and Safety Contemplations

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic as of March 2020, creating a global crisis and claiming millions of lives. To halt the pandemic and alleviate its impact on society, economy, and public health, the development of vaccines and antiviral agents against SARS-CoV-2 was a dire need. To date, various platforms have been utilized for SARSCoV-2 vaccine development, and over 200 vaccine candidates have been produced, many of which have obtained the United States Food and Drug Administration (FDA) approval for emergency use. Despite this successful development and licensure, concerns regarding the safety and efficacy of these vaccines have arisen, given the unprecedented speed of vaccine development and the newly emerging SARS-CoV-2 strains and variants. In this review, we summarize the different platforms used for Coronavirus Disease 2019 (COVID-19) vaccine development, discuss their strengths and limitations, and highlight the major safety concerns and potential risks associated with each vaccine type

COVID-19 Vaccination: The Mainspring of Challenges and the Seed of Remonstrance

As of March 2020, the time when the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic, our existence has been threatened and the lives of millions have been claimed. With this ongoing global issue, vaccines are considered of paramount importance in curtailing the outbreak and probably a prime gamble to bring us back to ‘ordinary life’. To date, more than 200 vaccine candidates have been produced, many of which were approved by the Food and Drug Administration (FDA) for emergency use, with the research and discovery phase of their production process passed over. Capering such a chief practice in COVID-19 vaccine development, and manufacturing vaccines at an unprecedented speed brought many challenges into play and raised COVID-19 vaccine remonstrance. In this review, we highlight relevant challenges to global COVID-19 vaccine development, dissemination, and deployment, particularly at the level of large-scale production and distribution. We also delineate public perception on COVID-19 vaccination and outline the main facets affecting people’s willingness to get vaccinated

Validation of Selected Commercial Serological Assays for Diagnosis of COVID-19

As researchers around the globe rush to put the available antibody tests to use, concerns have been raised about their precision. This study aimed to evaluate and compare the performance of selected commercial & automated serological assays, that are widely used in different clinical settings in Qatar. We validated the performance of five commercial IgG and IgM ELISA kits, three fully automated immunoassays, and two commercial rapid tests. The sensitivity of all assays was compared to RT-PCR and a surrogate virus neutralization test (sVNT). In addition, cross-reactivity was investigated. Among the evaluated kits, Lionex IgG assaydemonstrated the best performance (~88% sensitivity and ~99 specificity). All automated assays showed an excellent correlation with the neutralization test with an overall agreement of 93.6-98.5%. The rapid assays demonstrated a very good performance in detecting IgG antibodies (86.0-88.0% sensitivity and 98.0-100% specificity)

Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2

The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19

Organ-specific toxicity evaluation of stearamidopropyl dimethylamine (SAPDMA) surfactant using zebrafish embryos

Surfactants are widely used in the industry of detergents, household products, and cosmetics. SAPDMA is a cationic surfactant that is used mostly in cosmetics, conditioning agents and has recently gained attention as a corrosion inhibitor in the sea pipelines industry. In this regard, literature concerning the ecotoxicological classification of SAPDMA on aquatic animals is lacking. This study aims to evaluate the potential ecotoxicity of SAPDMA using the aquatic zebrafish embryo model. The potential toxic effects of SAPDMA were assessed by different assays. This includes (i) mortality/survival assay to assess the median lethal concentration (LC50); (ii) teratogenicity assay to assess the no observed effect concentration (NOEC); (iii) organ-specific toxicity assays including cardiotoxicity, neurotoxicity (using locomotion assay), hematopoietic toxicity (hemoglobin synthesis using o-dianisidine staining), hepatotoxicity (liver steatosis and yolk retention using Oil Red O (ORO) stain); (iv) cellular cytotoxicity (mitochondrial membrane potential) by measuring the accumulation of JC-1 dye into mitochondria. Exposure of embryos to SAPDMA caused mortality in a dose-dependent manner with a calculated LC50 of 2.3 mg/L. Thus, based on the LC50 value and according to the Fish and Wildlife Service (FWS) Acute Toxicity Rating Scale, SAPDMA is classified as “moderately toxic”. The No Observed Effect Concentration (NOEC) concerning a set of parameters including scoliosis, changes in body length, yolk, and eye sizes was 0.1 mg/L. At the same NOEC concentration (0.1 mg/L), no organ-specific toxicity was detected in fish treated with SAPDMA, except hepatomegaly with no associated liver dysfunctions. However, higher SAPDMA concentrations (0.8 mg/L) have dramatic effects on zebrafish organ development (eye, heart, and liver development). Our data recommend a re-evaluation of the SAPDMA employment in the industry setting and its strictly monitoring by environmental and public health agencies

Diagnostic Efficiency of Three Fully Automated Serology Assays and Their Correlation with a Novel Surrogate Virus Neutralization Test in Symptomatic and Asymptomatic SARS-COV-2 Individuals

Abstract: To support the deployment of serology assays for population screening during the COVID-19 pandemic, we compared the performance of three fully automated SARS-CoV-2 IgG assays: Mindray CL-900i® (target: spike [S] and nucleocapsid [N]), BioMérieux VIDAS®3 (target: receptor-binding domain [RBD]) and Diasorin LIAISON®XL (target: S1 and S2 subunits). A total of 111 SARS-CoV-2 RT-PCR- positive samples collected at ≥ 21 days post symptom onset, and 127 prepandemic control samples were included. Diagnostic performance was assessed in correlation to RT-PCR and a surrogate virus-neutralizing test (sVNT). Moreover, cross-reactivity with other viral antibodies was investigated. Compared to RT-PCR, LIAISON®XL showed the highest overall specificity (100%), followed by VIDAS®3 (98.4%) and CL-900i® (95.3%). The highest sensitivity was demonstrated by CL-900i® (90.1%), followed by VIDAS®3 (88.3%) and LIAISON®XL (85.6%). The sensitivity of all assays was higher in symptomatic patients (91.1–98.2%) compared to asymptomatic patients (78.4–80.4%). In correlation to sVNT, all assays showed excellent sensitivities (92.2–96.1%). In addition, VIDAS®3 demonstrated the best correlation (r = 0.75) with the sVNT. The present study provides insights on the performance of three fully automated assays, which could help diagnostic laboratories in the choice of a particular assay according to the intended us

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies

ObjectivesTo evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. Methods70 negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptoms onset: ≤7, 8-14, and >14 days) were used to compare the sensitivity, specificity, agreement, positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. ResultsLionex showed the highest specificity (98.6%, 95%CI: 92.3-99.8), followed by EDI and Dia.Pro (97.1%, 95%CI: 90.2-99.2), NovaTec (85.7%, 95%CI: 75.7-92.1), then AnshLabs (75.7%, 95%CI: 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG positive sample except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptoms onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95%CI: 72.7-95.2) and 86.4% (95%CI: 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen’s kappa was as follows: Lionex (0.89)> NovaTec (0.70)> Dia.Pro (0.69)> AnshLabs (0.63)> EDI (0.55). ConclusionThe Lionex ELISA, which measures antibodies solely to the S1 protein, demonstrated the best performance.This work was made possible by grant No. RRC-2-032 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors. GKN would like to acknowledge funds from Qatar University's internal grant QUERG-CMED-2020-2

Are commercial antibody assays substantially underestimating SARS-CoV-2 ever infection? An analysis on a population-based sample in a high exposure setting

AbstractBackgroundPerformance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 ever (past or current) infection in a population-based sample in a high exposure setting.MethodsPCR and serological testing was performed on 394 individuals.ResultsSARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1%-47.8%), 40.6% (95% CI 35.9%-45.5%), and 42.4% (95% CI 37.6%-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2%-95.7%, 89.3%-92.8%, and 93.8%-97.8%, respectively; Cohen kappa statistic ranged from 0.86-0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6%-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9%-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9%-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively.ConclusionsAll three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.</jats:sec

Effectiveness of Convalescent Plasma Therapy in COVID-19 Patients with Hematological Malignancies: A Systematic Review

Background: Immunocompromised patients, including those with hematological malignancies, are at a high risk of developing severe coronavirus disease 2019 (COVID-19) complications. Currently, there is a limited number of systematic reviews into the efficacy of convalescent plasma therapy (CPT) use in the treatment of COVID-19 patients with hematological malignancies. Therefore, the aim of this review was to systematically appraise the current evidence for the clinical benefits of this therapy in COVID-19 patients with hematological malignancies. Methods: A comprehensive search was conducted up to April 2022, using four databases: PubMed, Web of Science, Science Direct, and Scopus. Two reviewers independently assessed the quality of the included studies. Data collection analysis was performed using Microsoft Excel 365 and GraphPad Prism software. Results: 18 studies met the inclusion criteria; these records included 258 COVID-19 patients who had hematological malignancies and were treated with CPT. The main findings from the reviewed data suggest that CPT may be associated with improved clinical outcomes, including (a) higher survival rate, (b) improved SARS-CoV-2 clearance and presence of detectable anti-SARS-CoV-2 antibodies post CP transfusion, and (c) improved hospital discharge time and recovery after 1 month of CPT. Furthermore, treatment with convalescent plasma was not associated with the development of adverse events. Conclusions: CPT appears to be an effective supportive therapeutic option for hematological malignancy patients infected with COVID-19. To our knowledge, this is one of the first systematic reviews of the clinical benefits of CPT in COVID-19 patients with hematological malignancies