Improved diagnosis of SARS-CoV-2 by using Nucleoprotein and Spike protein fragment 2 in quantitative dual ELISA tests

The novel Coronavirus, SARS-CoV-2, is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and Spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative ELISA assays that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive COVID-19 cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients that had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.

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Considerations for Obstetric Care during the COVID-19 Pandemic

American Journal of Perinatology ◽

10.1055/s-0040-1710051 ◽

2020 ◽

Vol 37 (08) ◽

pp. 773-779 ◽

Cited By ~ 5

Author(s):

Sarah K. Dotters-Katz ◽

Brenna L. Hughes

Keyword(s):

Severe Disease ◽

Herd Immunity ◽

Obstetric Care ◽

The Novel ◽

Intensive Care Admission ◽

Care Workers ◽

Increased Risk ◽

Key Points ◽

High Risk Populations ◽

Novel Coronavirus

The novel coronavirus disease 2019 (COVID-19) is a growing pandemic that is impacting daily life across the globe. Though disease is often mild, in high-risk populations, severe disease often leads to intubation, intensive care admission (ICU) admission, and in many cases death. The implications for pregnancy remain largely unknown. Early data suggest that COVID-19 may not pose increased risk in the pregnant population. Vertical transmission has not been confirmed. Because no treatment, no vaccine and no herd immunity exist, social distancing is the best mechanism available to protect patients and health care workers from infection. This review will discuss what is known about the virus as it relates to pregnancy and then consider management considerations based on these data. Key Points

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Epidemiological impact of SARS-CoV-2 vaccination: mathematical modeling analyses

10.1101/2020.04.19.20070805 ◽

2020 ◽

Cited By ~ 5

Author(s):

Monia Makhoul ◽

Houssein H. Ayoub ◽

Hiam Chemaitelly ◽

Shaheen Seedat ◽

Ghina R Mumtaz ◽

...

Keyword(s):

Decision Making ◽

Disease Progression ◽

Vaccine Development ◽

Severe Disease ◽

Herd Immunity ◽

Social Contact ◽

Population Level ◽

Contact Rate ◽

Disease Case ◽

Vaccine Impact

AbstractBackgroundSeveral SARS-CoV-2 vaccine candidates are currently in the pipeline. This study aims to inform SARS-CoV-2 vaccine development, licensure, decision-making, and implementation by determining key preferred vaccine product characteristics and associated population-level impact.MethodsVaccination impact was assessed at various efficacies using an age-structured mathematical model describing SARS-CoV-2 transmission and disease progression, with application for China.ResultsA prophylactic vaccine with efficacy against acquisition (VES) of ≥70% is needed to eliminate this infection. A vaccine with VES <70% will still have a major impact, and may control the infection if it reduces infectiousness or infection duration among those vaccinated who acquire the infection, or alternatively if supplemented with a moderate social-distancing intervention (<20% reduction in contact rate), or complemented with herd immunity. Vaccination is cost-effective. For a vaccine with VES of 50%, number of vaccinations needed to avert one infection is only 2.4, one severe disease case is 25.5, one critical disease case is 33.2, and one death is 65.1. Gains in effectiveness are achieved by initially prioritizing those ≥60 years. Probability of a major outbreak is virtually zero with a vaccine with VES ≥70%, regardless of number of virus introductions. Yet, an increase in social contact rate among those vaccinated (behavior compensation) can undermine vaccine impact.ConclusionsEven a partially-efficacious vaccine can offer a fundamental solution to control SARS-CoV-2 infection and at high cost-effectiveness. In addition to the primary endpoint on infection acquisition, developers should assess natural history and disease progression outcomes and/or proxy biomarkers, since such secondary endpoints may prove critical in licensure, decision-making, and vaccine impact.

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Contact Tracing Applications Against COVID-19: A Systematic Review (Preprint)

10.2196/preprints.30262 ◽

2021 ◽

Author(s):

Ahmad Nabeel ◽

Salman AlSabah ◽

Eliana Al Haddad ◽

Hutan Ashrafian

Keyword(s):

Systematic Review ◽

Critical Mass ◽

Population Level ◽

Ease Of Use ◽

Contact Tracing ◽

The Novel ◽

Scientific Databases ◽

Manual Methods ◽

Novel Coronavirus ◽

Transmission Of Disease

BACKGROUND The novel coronavirus 2019 (COVID-19) pandemic has triggered public anxiety around the world. So far, the evidence suggests that prevention on a public scale is the most effective health measure for thwarting the progress of COVID-19. Another critical aspect of preventing COVID-19 is contact tracing. OBJECTIVE We aimed to investigate the effectiveness of contact tracing applications currently available in the context of the COVID-19 pandemic. METHODS We undertook a systematic review and narrative synthesis of all literature relating to contact tracing applications in the context of COVID-19. We searched 3 major scientific databases. Only articles that were published in English and were available as full-text articles were selected for review. Data were extracted and narrative syntheses conducted. RESULTS Five studies relating to COVID-19 were included in the review. Our results suggest that digitalized contact tracing methods can be beneficial for impeding the progress of COVID-19. Three key themes were generated from this systematic review. First, the critical mass of application adoption must be attained at the population level before the sensitivity and positive predictive value of the solution can be increased. Second, usability factors such as access, ease of use and the elimination of barriers are essential in driving this uptake. Third, privacy must be ensured where possible as it is the single most significant barrier against achieving critical mass. CONCLUSIONS The COVID-19 pandemic has claimed more than 2 million lives globally, with over 100 million confirmed cases. Contact tracing can rapidly identify potentially infected individuals before the emergence of severe or critical symptoms, and it can also prevent the subsequent transmission of disease from secondary cases when implemented efficiently. Contact tracing methods have proved to be beneficial for impeding the progress of COVID-19 as compared to older, more labor intensive manual methods.

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Epidemiological Impact of SARS-CoV-2 Vaccination: Mathematical Modeling Analyses

Vaccines ◽

10.3390/vaccines8040668 ◽

2020 ◽

Vol 8 (4) ◽

pp. 668 ◽

Cited By ~ 2

Author(s):

Monia Makhoul ◽

Houssein H. Ayoub ◽

Hiam Chemaitelly ◽

Shaheen Seedat ◽

Ghina R. Mumtaz ◽

...

Keyword(s):

Mathematical Modeling ◽

Vaccine Development ◽

Severe Disease ◽

Herd Immunity ◽

Social Contact ◽

Population Level ◽

Contact Rate ◽

Disease Case ◽

Major Outbreak ◽

Vaccine Impact

This study aims to inform SARS-CoV-2 vaccine development/licensure/decision-making/implementation, using mathematical modeling, by determining key preferred vaccine product characteristics and associated population-level impacts of a vaccine eliciting long-term protection. A prophylactic vaccine with efficacy against acquisition (VES) ≥70% can eliminate the infection. A vaccine with VES <70% may still control the infection if it reduces infectiousness or infection duration among those vaccinated who acquire the infection, if it is supplemented with <20% reduction in contact rate, or if it is complemented with herd-immunity. At VES of 50%, the number of vaccinated persons needed to avert one infection is 2.4, and the number is 25.5 to avert one severe disease case, 33.2 to avert one critical disease case, and 65.1 to avert one death. The probability of a major outbreak is zero at VES ≥70% regardless of the number of virus introductions. However, an increase in social contact rate among those vaccinated (behavior compensation) can undermine vaccine impact. In addition to the reduction in infection acquisition, developers should assess the natural history and disease progression outcomes when evaluating vaccine impact.

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Outpatient management of heart valve disease following the COVID-19 pandemic: implications for present and future care

Heart ◽

10.1136/heartjnl-2020-317600 ◽

2020 ◽

Vol 106 (20) ◽

pp. 1549-1554 ◽

Cited By ~ 1

Author(s):

Benoy Nalin Shah ◽

Dominik Schlosshan ◽

Hannah Zelie Ruth McConkey ◽

Mamta Heena Buch ◽

Andrew John Marshall ◽

...

Keyword(s):

Heart Valve ◽

Waiting Times ◽

Severe Disease ◽

Valve Disease ◽

Heart Valve Disease ◽

The Novel ◽

Future Care ◽

Novel Coronavirus

The established processes for ensuring safe outpatient surveillance of patients with known heart valve disease (HVD), echocardiography for patients referred with new murmurs and timely delivery of surgical or transcatheter treatment for patients with severe disease have all been significantly impacted by the novel coronavirus pandemic. This has created a large backlog of work and upstaging of disease with consequent increases in risk and cost of treatment and potential for worse long-term outcomes. As countries emerge from lockdown but with COVID-19 endemic in society, precautions remain that restrict ‘normal’ practice. In this article, we propose a methodology for restructuring services for patients with HVD and provide recommendations pertaining to frequency of follow-up and use of echocardiography at present. It will be almost impossible to practice exactly as we did prior to the pandemic; thus, it is essential to prioritise patients with the greatest clinical need, such as those with symptomatic severe HVD. Local procedural waiting times will need to be considered, in addition to usual clinical characteristics in determining whether patients requiring intervention would be better suited having surgical or transcatheter treatment. We present guidance on the identification of stable patients with HVD that could have follow-up deferred safely and suggest certain patients that could be discharged from follow-up if waiting lists are triaged with appropriate clinical input. Finally, we propose that novel models of working enforced by the pandemic—such as increased use of virtual clinics—should be further developed and evaluated.

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Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure.

10.1101/2020.08.14.20174490 ◽

2020 ◽

Cited By ~ 6

Author(s):

Tyler J Ripperger ◽

Jennifer L Uhrlaub ◽

Makiko Watanabe ◽

Rachel Wong ◽

Yvonne Castaneda ◽

...

Keyword(s):

Local Community ◽

Severe Disease ◽

Neutralizing Antibody ◽

Population Level ◽

Population Exposure ◽

Antibody Titers ◽

Asymptomatic Individuals ◽

Humoral Responses ◽

Antibody Levels ◽

Antibody Kinetics

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.

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The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

PLoS Pathogens ◽

10.1371/journal.ppat.1010162 ◽

2021 ◽

Vol 17 (12) ◽

pp. e1010162

Author(s):

Alexandra Melton ◽

Lara A. Doyle-Meyers ◽

Robert V. Blair ◽

Cecily Midkiff ◽

Hunter J. Melton ◽

...

Keyword(s):

T Cells ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Macaca Nemestrina ◽

The Novel ◽

Pigtail Macaque ◽

Immunodeficiency Virus ◽

Cytotoxic Molecules ◽

Pathologic Lesions ◽

Novel Coronavirus

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

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Assessment of Anti-SARS CoV-2 seroprevalence in habitants of Assam (AASSHA): report of the first serosurvey in Assam

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20211780 ◽

2021 ◽

Vol 8 (5) ◽

pp. 2490

Author(s):

Jyotismita Pathak ◽

Mridusmita Das ◽

Khalil Siddique

Keyword(s):

Public Health ◽

Severe Acute Respiratory Syndrome ◽

Herd Immunity ◽

Health Policies ◽

The Novel ◽

Blood Samples ◽

Public Health Policies ◽

Novel Coronavirus

Background: Today, there is a pressing need to identify the proportion of people immune to the infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) so that public health policies can be formulated accordingly for the ongoing COVID-19 pandemic. Keeping this in mind, we designed a serosurvey in Assam with aims to estimate the prevalence of infection as well as the infection to case ratio of the novel coronavirus in Assam.Methods: A total of 9 districts belonging to three different strata of districts were randomly selected for the study. In these selected districts, blood samples were collected from a sample of population and were checked for the antibodies (IgG type). Those testing reactive for the mentioned antibodies were considered to have been infected ever before the onset of the study.Results: A total of 2390 study subjects were tested for the presence of antibodies against the SARS-CoV-2. The proportion of people harboring antibodies against the infection was found to be 23.7 percent.Conclusions: The serosurvey revealed that the proportion of people having antibodies was lower than that required for attaining herd immunity levels in a population. The case to infection ratios reveal that there is a large chunk of population who didn’t know about their infection.

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COVID-19-Related Web Search Behaviors and Infodemic Attitudes in Italy: Infodemiological Study (Preprint)

10.2196/preprints.19374 ◽

2020 ◽

Author(s):

Alessandro Rovetta ◽

Akshaya Srikanth Bhagavathula

Keyword(s):

Web Search ◽

Population Level ◽

Google Trends ◽

The Novel ◽

Fake News ◽

Search Activity ◽

Campania Region ◽

Search Volume ◽

Government Websites ◽

Novel Coronavirus

BACKGROUND Since the beginning of the novel coronavirus disease (COVID-19) outbreak, fake news and misleading information have circulated worldwide, which can profoundly affect public health communication. OBJECTIVE We investigated online search behavior related to the COVID-19 outbreak and the attitudes of “infodemic monikers” (ie, erroneous information that gives rise to interpretative mistakes, fake news, episodes of racism, etc) circulating in Italy. METHODS By using Google Trends to explore the internet search activity related to COVID-19 from January to March 2020, article titles from the most read newspapers and government websites were mined to investigate the attitudes of infodemic monikers circulating across various regions and cities in Italy. Search volume values and average peak comparison (APC) values were used to analyze the results. RESULTS Keywords such as “novel coronavirus,” “China coronavirus,” “COVID-19,” “2019-nCOV,” and “SARS-COV-2” were the top infodemic and scientific COVID-19 terms trending in Italy. The top five searches related to health were “face masks,” “amuchina” (disinfectant), “symptoms of the novel coronavirus,” “health bulletin,” and “vaccines for coronavirus.” The regions of Umbria and Basilicata recorded a high number of infodemic monikers (APC weighted total >140). Misinformation was widely circulated in the Campania region, and racism-related information was widespread in Umbria and Basilicata. These monikers were frequently searched (APC weighted total >100) in more than 10 major cities in Italy, including Rome. CONCLUSIONS We identified a growing regional and population-level interest in COVID-19 in Italy. The majority of searches were related to amuchina, face masks, health bulletins, and COVID-19 symptoms. Since a large number of infodemic monikers were observed across Italy, we recommend that health agencies use Google Trends to predict human behavior as well as to manage misinformation circulation in Italy.

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Age-targeted dose allocation can halve COVID-19 vaccine requirements

10.1101/2020.10.08.20208108 ◽

2020 ◽

Author(s):

Michael T. Meehan ◽

Daniel G. Cocks ◽

Jamie M. Caldwell ◽

James M. Trauer ◽

Adeshina I. Adekunle ◽

...

Keyword(s):

Mathematical Model ◽

Severe Disease ◽

Herd Immunity ◽

Population Level ◽

Morbidity And Mortality ◽

Effective Strategy ◽

Risk Of Infection ◽

Middle Aged ◽

Contact Rates ◽

Age Structured

ABSTRACTIn anticipation of COVID-19 vaccine deployment, we use an age-structured mathematical model to investigate the benefits of optimizing age-specific dose allocation to suppress the transmission, morbidity and mortality of SARS-CoV-2 and the associated disease, COVID-19. To minimize transmission, we find that the highest priority individuals across 179 countries are typically those between 30 and 59 years of age because of their high contact rates and higher risk of infection and disease. Conversely, morbidity and mortality are initially most effectively reduced by targeting 60+ year olds who are more likely to experience severe disease. However, when population-level coverage is sufficient — such that herd immunity can be achieved through targeted dose allocation — prioritizing middle-aged individuals becomes the most effective strategy to minimize hospitalizations and deaths. For each metric considered, we show that optimizing the allocation of vaccine doses can more than double their effectiveness.

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