AMH Biotech https://amhbiotech.com/ Tue, 03 Feb 2026 16:45:09 +0000 en-US hourly 1 https://wordpress.org/?v=6.9.4 https://amhbiotech.com/wp-content/uploads/2024/01/cropped-0-32x32.png AMH Biotech https://amhbiotech.com/ 32 32 AMH Biotech LLC Announces Strategic Academic Research Collaborations https://amhbiotech.com/amh-biotech-llc-announces-strategic-academic-research-collaborations/ Tue, 03 Feb 2026 16:41:35 +0000 https://amhbiotech.com/?p=6220 AMH Biotech LLC is pleased to announce new research collaborations with the Sbarro Institute for Cancer Research at Temple University (Philadelphia, PA) and RowanUniversity (New Jersey). These partnerships reflect AMH Biotech’s commitment to advancing innovative and translational science at the intersection of academia and biotechnology. Through these collaborations, AMH Biotech will support interdisciplinary research efforts…

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AMH Biotech LLC is pleased to announce new research collaborations with the Sbarro Institute for Cancer Research at Temple University (Philadelphia, PA) and Rowan
University (New Jersey)
. These partnerships reflect AMH Biotech’s commitment to advancing innovative and translational science at the intersection of academia and biotechnology.

Through these collaborations, AMH Biotech will support interdisciplinary research efforts in cancer biology, precision medicine, and therapeutic target discovery. By combining AMH Biotech’s industry-driven translational focus with the deep scientific expertise and research infrastructure of its academic partners, these initiatives aim to accelerate the identification of novel cancer targets and enable the development of next-generation therapeutic strategies.

AMH Biotech LLC is proud to work alongside leading academic institutions to foster scientific innovation, train the next generation of researchers, and translate cutting-edge discoveries into meaningful clinical impact.

Ali Mohseni
AMH Biotech LLC
Founder & Principal Investigator
Email: [email protected]
Website: www.amhbiotech.com

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Global Health Strategies to Prevent the Spread of SARS-CoV-2 Variants in High-Risk Populations https://amhbiotech.com/global-health-strategies-to-prevent-the-spread-of-sars-cov-2-variants-in-high-risk-populations/ Thu, 03 Apr 2025 19:30:41 +0000 https://amhbiotech.com/?p=6002 As SARS-CoV-2 continues to evolve, new variants present ongoing challenges to public health systems worldwide. While global vaccination campaigns and improved diagnostics have played a significant role in reducing the overall impact of COVID-19, high-risk populations—such as the elderly, immunocompromised individuals, and people with chronic health conditions—remain especially vulnerable. To effectively mitigate the spread of…

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As SARS-CoV-2 continues to evolve, new variants present ongoing challenges to public health systems worldwide. While global vaccination campaigns and improved diagnostics have played a significant role in reducing the overall impact of COVID-19, high-risk populations—such as the elderly, immunocompromised individuals, and people with chronic health conditions—remain especially vulnerable.

To effectively mitigate the spread of SARS-CoV-2 variants in these groups, coordinated global strategies are essential. Below are key approaches that can support this mission:


1. Enhanced Genomic Surveillance

Tracking mutations in the virus is crucial. Countries must invest in genomic sequencing to detect emerging variants early. Collaborative platforms like GISAID allow researchers to share data in real time, enabling faster risk assessment and response.


2. Targeted Booster Vaccination Campaigns

High-risk populations benefit most from updated booster shots, especially those designed to address dominant variants. Health authorities must prioritize these groups for timely and accessible vaccination drives.


3. Intranasal and Mucosal Vaccine Development

Emerging vaccine technologies, particularly intranasal vaccines, show promise in blocking viral entry at mucosal sites. These vaccines could offer additional layers of protection for individuals with reduced systemic immune responses.


4. Widespread Use of Rapid Diagnostic Tools

Rapid and accurate diagnostics—particularly point-of-care tests—are essential for early detection and isolation. Saliva-based and non-invasive tests are ideal for use in elder care facilities, outpatient clinics, and underserved areas.


5. Global Distribution Equity

Ensuring equitable access to vaccines, treatments, and diagnostics across regions reduces the chances of variant spread and emergence. Global cooperation through COVAX and similar initiatives remains vital.


6. Reinforcing Infection Control in High-Risk Environments

Nursing homes, dialysis centers, and hospitals must maintain robust infection control protocols. Regular screening of healthcare workers and improved ventilation systems play a significant role in minimizing outbreaks.


7. Public Communication and Education

Accurate, science-based public communication builds trust. Campaigns should address vaccine hesitancy, proper mask usage, and early symptom recognition, particularly targeting caregivers and families of high-risk individuals.


8. Flexible Policy Frameworks

Policies must adapt quickly to emerging data. Quarantine guidelines, travel restrictions, and public health mandates should be region-specific and informed by local epidemiological trends.


9. Support for Long COVID Clinics and Research

High-risk individuals are more likely to experience long-term effects from infection. Investments in long COVID research and dedicated care centers ensure better outcomes and reduce long-term burden on health systems.


10. Integration of Digital Health Tools

Telemedicine, mobile apps, and AI-driven risk prediction models can help monitor high-risk patients remotely. These technologies reduce hospital visits and allow for prompt intervention when symptoms escalate.


Conclusion
The fight against SARS-CoV-2 is far from over, particularly for those most susceptible to severe illness. AMH Biotech remains committed to supporting innovative, science-driven solutions that safeguard high-risk populations. Through continued research, collaboration, and community engagement, we can build a more resilient and responsive global health system.

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Development and Efficacy of Intranasal Vaccines Against Emerging Respiratory Viruses https://amhbiotech.com/development-and-efficacy-of-intranasal-vaccines-against-emerging-respiratory-viruses/ Sun, 23 Mar 2025 19:28:22 +0000 https://amhbiotech.com/?p=5999 As the world continues to face the evolving threat of respiratory viruses, researchers and pharmaceutical companies are exploring innovative vaccination strategies to improve prevention and control. One of the most promising developments in this area is the use of intranasal vaccines—an approach that could revolutionize how we fight airborne diseases like influenza, RSV, and even…

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As the world continues to face the evolving threat of respiratory viruses, researchers and pharmaceutical companies are exploring innovative vaccination strategies to improve prevention and control. One of the most promising developments in this area is the use of intranasal vaccines—an approach that could revolutionize how we fight airborne diseases like influenza, RSV, and even variants of SARS-CoV-2.

Why Intranasal Vaccines?

Traditional intramuscular vaccines are highly effective, but they primarily stimulate a systemic immune response. In contrast, respiratory viruses typically enter the body through the nasal mucosa, making mucosal immunity a critical first line of defense.

Intranasal vaccines are designed to trigger an immune response directly in the nasopharyngeal region, providing localized protection where the virus first makes contact. This mucosal immunity can significantly reduce viral transmission and infection severity.

Recent Advancements in Intranasal Vaccine Technology

The development of intranasal vaccines has accelerated in recent years, with several candidates showing promise in both preclinical and clinical trials:

  • Live-attenuated and recombinant viral vector platforms are being used to safely deliver antigens to the mucosal surface.
  • Some formulations incorporate adjuvants that enhance the mucosal immune response without causing excessive inflammation.
  • Notably, studies have shown that intranasal vaccines can produce both IgA antibodies in the mucosa and systemic IgG antibodies, offering a dual layer of protection.

Efficacy Against Emerging Variants

Emerging variants of viruses like SARS-CoV-2 continue to challenge vaccine efficacy. However, intranasal vaccines have demonstrated potential in:

  • Blocking viral entry by neutralizing the virus at its point of entry.
  • Reducing asymptomatic spread, especially in animal models.
  • Providing cross-protection against different variants due to the broad immune activation in the mucosa.

Benefits Over Traditional Vaccines

  • Needle-free delivery increases vaccine acceptance and reduces the need for trained personnel.
  • Lower production and distribution costs, especially in low-resource settings.
  • Easier administration in mass vaccination campaigns, schools, and public health emergencies.

Future Outlook

While intranasal vaccines are still under development, early results are encouraging. As more data becomes available, this method may become a cornerstone in preventing future respiratory pandemics. Collaborative efforts between researchers, biotech companies, and public health institutions will be key in bringing these innovations to market.

At AMH Biotech, we continue to monitor and support advancements in vaccine technology, advocating for science-driven solutions to global health challenges.

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Evaluation of Saliva-Based Diagnostic Tests for Widespread Screening of Infectious Diseases https://amhbiotech.com/evaluation-of-saliva-based-diagnostic-tests-for-widespread-screening-of-infectious-diseases/ Fri, 14 Mar 2025 12:43:37 +0000 https://amhbiotech.com/?p=5993 As the world continues to adapt to the evolving landscape of infectious diseases, the demand for rapid, non-invasive, and scalable diagnostic tools has never been more pressing. Saliva-based diagnostic testing has emerged as a promising alternative to traditional methods, offering convenience without compromising accuracy. At AMH Biotech, we delve into the growing relevance and potential…

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As the world continues to adapt to the evolving landscape of infectious diseases, the demand for rapid, non-invasive, and scalable diagnostic tools has never been more pressing. Saliva-based diagnostic testing has emerged as a promising alternative to traditional methods, offering convenience without compromising accuracy. At AMH Biotech, we delve into the growing relevance and potential of saliva diagnostics in transforming public health screening and surveillance.

Why Saliva?

Saliva is an easily accessible and non-invasive biofluid, making it ideal for mass screening efforts. Unlike nasopharyngeal swabs or blood tests, saliva collection does not require specialized healthcare professionals or invasive procedures. This reduces the risk of virus transmission to frontline workers and enhances patient compliance—particularly in pediatric, elderly, and high-risk populations.

Accuracy and Efficacy

Recent studies have demonstrated that saliva-based molecular tests can detect a range of pathogens with a high degree of sensitivity and specificity. From SARS-CoV-2 to influenza and other respiratory viruses, saliva has shown robust viral detection capabilities when paired with advanced molecular diagnostic technologies such as RT-PCR and CRISPR-based assays.

In comparative analyses, saliva testing has often yielded results that are comparable—and sometimes superior—to nasal swab testing, especially during early stages of infection when viral load is higher in the oral cavity.

Scalability and Accessibility

One of the greatest strengths of saliva diagnostics is scalability. Saliva collection kits can be easily distributed and used at home, in schools, workplaces, or community testing centers. This decentralization of testing reduces pressure on healthcare systems and enables broader surveillance of infectious diseases across urban and rural areas alike.

Additionally, saliva samples are stable at room temperature for several hours, simplifying transportation and storage logistics—an essential factor in resource-limited settings.

Applications Beyond COVID-19

While COVID-19 has accelerated the development and adoption of saliva-based tests, their utility extends far beyond the pandemic. Saliva diagnostics are being explored for detecting diseases such as tuberculosis, HIV, Zika virus, and even certain types of cancer. The versatility of this method highlights its potential to become a cornerstone of future diagnostic strategies.

Challenges and Considerations

Despite its advantages, saliva testing is not without limitations. Factors such as eating, drinking, or smoking prior to sample collection can affect test accuracy. Standardization of collection methods and assay optimization remain critical to ensure consistent results across diverse populations and pathogens.

The Future of Saliva-Based Diagnostics

At AMH Biotech, we are committed to supporting innovation in diagnostic solutions that prioritize accessibility, accuracy, and patient experience. Saliva-based testing stands at the forefront of this movement, offering a transformative approach to disease detection and public health management.

As technology advances, we envision a future where rapid, non-invasive testing is integrated into routine healthcare—empowering individuals and communities to take control of their health with ease and confidence.

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Advancements in Point-of-Care Molecular Diagnostics for Early Detection of Emerging Viral Threats https://amhbiotech.com/advancements-in-point-of-care-molecular-diagnostics-for-early-detection-of-emerging-viral-threats/ Tue, 25 Feb 2025 16:26:04 +0000 https://amhbiotech.com/?p=5978 In recent years, the rapid spread of viral infections like COVID-19, influenza, and respiratory syncytial virus (RSV) has highlighted the urgent need for efficient and accurate diagnostic tools. Early detection is critical for controlling the spread of infectious diseases and ensuring timely treatment, especially in the context of viral threats that evolve quickly. Point-of-care molecular…

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In recent years, the rapid spread of viral infections like COVID-19, influenza, and respiratory syncytial virus (RSV) has highlighted the urgent need for efficient and accurate diagnostic tools. Early detection is critical for controlling the spread of infectious diseases and ensuring timely treatment, especially in the context of viral threats that evolve quickly. Point-of-care molecular diagnostics are emerging as a game-changing solution, offering real-time detection and results at or near the patient’s location. This technology is revolutionizing how we respond to emerging viral threats and shaping the future of healthcare.

What Are Point-of-Care Molecular Diagnostics?

Point-of-care (POC) molecular diagnostics refer to testing methods that enable healthcare professionals to quickly and accurately diagnose diseases at the site of patient care, such as a clinic, doctor’s office, or even a remote location. These tests focus on detecting the genetic material (RNA or DNA) of viruses, using techniques like polymerase chain reaction (PCR) or isothermal amplification. Unlike traditional laboratory-based diagnostics, POC molecular tests can deliver results in minutes to hours, allowing for faster decision-making in clinical settings.

Key Advancements in Point-of-Care Molecular Diagnostics

  1. Speed and Efficiency
    Traditional laboratory tests can take several hours or days to deliver results, which may delay critical decisions regarding patient care. POC molecular diagnostics significantly reduce this turnaround time, often providing results within 30 minutes to an hour. This improvement is especially beneficial during outbreaks of fast-spreading viral infections, where time is of the essence.
  2. Accuracy and Sensitivity
    Early POC tests were often limited in terms of accuracy compared to lab-based tests. However, recent advancements in molecular technology have bridged that gap. Current POC diagnostics can achieve a high degree of sensitivity and specificity, detecting even small amounts of viral RNA or DNA. This minimizes the risk of false negatives and ensures that patients receive the right diagnosis the first time.
  3. Portability and Accessibility
    One of the greatest benefits of POC molecular diagnostics is their portability. Many new devices are compact and easy to use, making them ideal for use in remote areas or in situations where access to central laboratories is limited. This has opened up new possibilities for viral surveillance in low-resource settings, particularly in developing countries where healthcare infrastructure may be under strain.
  4. Multiplex Testing Capabilities
    Another significant advancement is the development of multiplex POC tests, which can detect multiple viruses or pathogens from a single sample. This is especially valuable in respiratory infections, where symptoms can overlap between viruses like influenza, RSV, and SARS-CoV-2. By offering a comprehensive diagnosis from a single test, multiplex diagnostics streamline the process and improve clinical outcomes.
  5. Integration with Digital Health Technologies
    The integration of POC diagnostics with digital health platforms is another exciting development. Many modern POC devices are now equipped with wireless connectivity, allowing results to be transmitted instantly to healthcare providers or public health databases. This enables real-time surveillance of viral outbreaks and ensures rapid response to emerging threats, improving overall public health management.

The Role of Point-of-Care Diagnostics in Emerging Viral Threats

As global travel increases and urbanization expands, the risk of viral pandemics and emerging infectious diseases grows. Point-of-care molecular diagnostics offer a critical tool for combating these challenges by enabling early detection and rapid containment. The ability to diagnose infections quickly on-site can help prevent the spread of contagious diseases in both healthcare settings and communities.

During the COVID-19 pandemic, POC diagnostics played a vital role in identifying cases, especially in areas with limited access to traditional lab facilities. This success has led to further investment in POC technology, spurring the development of even more advanced systems that can be applied to future viral threats.

Conclusion

The advancements in point-of-care molecular diagnostics are revolutionizing how we detect and respond to emerging viral threats. These innovations allow for faster, more accurate, and accessible testing, helping healthcare providers and public health officials stay ahead of infectious diseases. As technology continues to evolve, POC molecular diagnostics will play an increasingly important role in global health, offering a powerful tool to safeguard populations from the next viral outbreak.

At AMH Biotech, we are committed to staying at the forefront of these developments. By harnessing the power of cutting-edge diagnostics, we aim to support healthcare professionals in their fight against emerging viral threats and contribute to building a safer, healthier world. Stay tuned for more updates on our research and innovations in this space.

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Surging Emergence of Respiratory Virus Cases in China, Europe and US. https://amhbiotech.com/surging-emergence-of-respiratory-virus-cases-in-china-europe-and-us/ Fri, 17 Jan 2025 13:40:34 +0000 https://amhbiotech.com/?p=5931 The recent surge in respiratory virus cases in China and Europe has raised concerns about the potential for another pandemic. In China, hospitals in more than three major cities in the northern region have been overwhelmed by the influx of infected patients. Initially referred to as “pneumonia of unknown origin” by Chinese authorities, the cause…

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The recent surge in respiratory virus cases in China and Europe has raised concerns about the potential for another pandemic. In China, hospitals in more than three major cities in the northern region have been overwhelmed by the influx of infected patients. Initially referred to as “pneumonia of unknown origin” by Chinese authorities, the cause of the outbreak has now been identified as human metapneumovirus (hMPV).
hMPV, first discovered in 2001, has a history of causing significant outbreaks, including a major one in 2017. During that time, heightened hMPV activity was reported across North America, Europe, and parts of Asia, with genetic analyses revealing variability within its subgroups (A1, A2, B1, B2).
Recent Developments: The 2024-2025 hMPV Variant
The current outbreak, which began in late 2024, is marked by rapid transmission and severe symptoms, including pneumonia. Thousands of hospitalizations have been reported, with one notable instance being Tianjin Children’s Hospital, which recorded over 13,000 young patients in a single day across its outpatient and emergency departments.
While the genetic characteristics of the new hMPV subgroups have not yet been fully investigated, the symptoms and extended disease duration (ranging from 5 days to 3 weeks) suggest that the recent variants could be highly virulent. Notably, hMPV’s RNA-dependent RNA polymerase (RdRp) lacks a genetic proofreading mechanism, making the virus prone to mutations and the emergence of new variants.
Clinical Implications of hMPV Infection
hMPV can cause severe bronchiolitis, bronchitis, and pneumonia, particularly in children and young adults. Its symptoms are often indistinguishable from those caused by respiratory syncytial virus (RSV). Initial infections typically occur in early childhood, but reinfections are common throughout life.
Due to the virus’s slow growth in cell culture, molecular diagnostic methods, such as reverse transcriptase polymerase chain reaction (RT-PCR), are the preferred approach for detecting hMPV.
Key Observations from Recent and Past Outbreaks
Geographical Spread: Reports of heightened hMPV activity have come from North America, Europe, and parts of Asia.
Healthcare Strain: in the US already Hospitals and clinics have experienced a significant increase in respiratory infections, especially among children, the elderly, and immunocompromised individuals.
 
Coinfections: The outbreak often coincides with other seasonal respiratory viruses, such as influenza, RSV, and non-SARS coronaviruses, complicating diagnosis and management.
Diagnostic Challenges: Coinfections make it difficult to attribute symptoms solely to hMPV, further straining healthcare resources.

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Epidemiological Impact of Universal Varicella Vaccination on Consecutive Emergency Department Visits for Varicella and Its Cost-Effectiveness Among Children https://amhbiotech.com/epidemiological-impact-of-universal-varicella-vaccination-on-consecutive-emergency-department-visits-for-varicella-and-its-cost-effectiveness-among-children/ Tue, 04 Oct 2022 16:35:00 +0000 https://amhbiotech.com/?p=5311 Varicella is highly contagious and endemic worldwide. Previous studies reported a dramatic decline in varicella incidence and varicella-related deaths after implementing universal varicella vaccination (VarV). However, its impact and cost-effectiveness remain unknown in single emergency department (ED). We retrospectively reviewed the clinical database of consecutive patients younger than 16 years presenting to our primary ED between…

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Varicella is highly contagious and endemic worldwide. Previous studies reported a dramatic decline in varicella incidence and varicella-related deaths after implementing universal varicella vaccination (VarV). However, its impact and cost-effectiveness remain unknown in single emergency department (ED). We retrospectively reviewed the clinical database of consecutive patients younger than 16 years presenting to our primary ED between January 1, 2011, and December 31, 2019. Of the 265,191 children presenting to our ED, 3,092 were clinically diagnosed with varicella. The annual number of varicella patients was approximately 500 before introduction of the universal two-dose VarV in October 2014, and it decreased to approximately 200 in 2019. The number of varicella patients younger than 1 year (not eligible for vaccination) also decreased. Regarding the cost-effectiveness of VarV, approximately JPY1.5 million (US$14,300) were saved annually by our center. However, our study showed a relatively large percentage of infected unvaccinated children presenting to our ED (59.0%). After implementation of the universal VarV, infection was mainly observed in older children (i.e., the unvaccinated generation). In conclusion, our data showed excellent universal VarV effectiveness and cost-effectiveness in the ED. Additionally, our data suggest that the VarV should be administered to all eligible older patients.

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Intranasal inhibitor blocks omicron and other variants of SARS-CoV-2 https://amhbiotech.com/intranasal-inhibitor-blocks-omicron-and-other-variants-of-sars-cov-2/ Thu, 01 Sep 2022 16:35:00 +0000 https://amhbiotech.com/?p=5310 The emergence of the SARS-CoV-2 Omicron variant capable of escaping neutralizing antibodies emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Nasal epithelium is rich in the ACE2 receptor and important for SARS-CoV-2 transmission by supporting early viral replication before seeding to the lung1. Intranasal administration of SARS-CoV-2 neutralizing antibodies…

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The emergence of the SARS-CoV-2 Omicron variant capable of escaping neutralizing antibodies emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Nasal epithelium is rich in the ACE2 receptor and important for SARS-CoV-2 transmission by supporting early viral replication before seeding to the lung1. Intranasal administration of SARS-CoV-2 neutralizing antibodies or antibody fragments has shown encouraging potential as a protective measure in animal models2-5. However, there remains a need for SARS-CoV-2 blocking agents that are more economical to produce in large scale, while less vulnerable to mutational variation in the neutralization epitopes of the viral Spike glycoprotein. Here we describe TriSb92, a highly manufacturable trimeric human nephrocystin SH3 domain-derived antibody mimetic targeted against a conserved region in the receptor-binding domain of the Spike. TriSb92 potently neutralizes SARS-CoV-2 and its variants of concern, including Delta and Omicron. Intranasal administration of a modest dose of TriSb92 (5 or 50 micrograms) as early as eight hours before the challenge with SARS-CoV-2 B.1.351 efficiently protected mice from infection. The target epitope of TriSb92 was defined by cryo-EM, which revealed triggering of a conformational shift in the Spike trimer rather than competition for ACE2 binding as the molecular basis of its strong inhibitory action. Our results highlight the potential of intranasal inhibitors in protecting susceptible individuals from SARS-CoV-2 infection, and describe a novel type of inhibitor that could be of use in addressing the challenge posed by the Omicron variant.

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Evaluation of saliva molecular point of care for detection of SARS-CoV-2 in ambulatory care https://amhbiotech.com/evaluation-of-saliva-molecular-point-of-care-for-detection-of-sars-cov-2-in-ambulatory-care/ Wed, 24 Aug 2022 16:35:00 +0000 https://amhbiotech.com/?p=5309 Background Rapid identification of SARS-Cov-2 infected individuals is a cornerstone for the control of virus spread. The sensitivity of SARS-CoV-2 RNA detection by RT-PCR is similar in saliva and nasopharyngeal swab. Rapid molecular point-of-care tests in saliva could facilitate, broaden and speed up the diagnosis. Methods We conducted a prospective study in two community COVID-19…

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Background

Rapid identification of SARS-Cov-2 infected individuals is a cornerstone for the control of virus spread. The sensitivity of SARS-CoV-2 RNA detection by RT-PCR is similar in saliva and nasopharyngeal swab. Rapid molecular point-of-care tests in saliva could facilitate, broaden and speed up the diagnosis.

Methods

We conducted a prospective study in two community COVID-19 screening centers to evaluate the performances of a CE-marked RT-LAMP assay (EasyCoV™) designed for the detection of SARS-CoV2 RNA from fresh saliva samples, compared to nasopharyngeal RT-PCR, to saliva RT-PCR and to nasopharyngeal antigen testing.

Results

Overall, 117 of the 1718 participants (7%) were tested positive with nasopharyngeal RT-PCR. Compared to nasopharyngeal RT-PCR, the sensitivity and specificity of the RT-LAMP assay in saliva were 34% and 97% respectively. The Ct values of nasopharyngeal RT-PCR were significantly lower in the 40 true positive subjects with saliva RT-LAMP (Ct 25.9) than in the 48 false negative subjects with saliva RT-LAMP (Ct 28.4) (p = 0.028). Considering six alternate criteria for reference test, including saliva RT-PCR and nasopharyngeal antigen, the sensitivity of saliva RT-LAMP ranged between 27 and 44%.

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Empirical evidence on the efficiency of backward contact tracing in COVID-19 https://amhbiotech.com/empirical-evidence-on-the-efficiency-of-backward-contact-tracing-in-covid-19/ Mon, 22 Aug 2022 16:03:00 +0000 https://amhbiotech.com/?p=5276 The emergence of the SARS-CoV-2 Omicron variant capable of escaping neutralizing antibodies emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Nasal epithelium is rich in the ACE2 receptor and important for SARS-CoV-2 transmission by supporting early viral replication before seeding to the lung1. Intranasal administration of SARS-CoV-2 neutralizing antibodies…

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The emergence of the SARS-CoV-2 Omicron variant capable of escaping neutralizing antibodies emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Nasal epithelium is rich in the ACE2 receptor and important for SARS-CoV-2 transmission by supporting early viral replication before seeding to the lung1. Intranasal administration of SARS-CoV-2 neutralizing antibodies or antibody fragments has shown encouraging potential as a protective measure in animal models2-5. However, there remains a need for SARS-CoV-2 blocking agents that are more economical to produce in large scale, while less vulnerable to mutational variation in the neutralization epitopes of the viral Spike glycoprotein. Here we describe TriSb92, a highly manufacturable trimeric human nephrocystin SH3 domain-derived antibody mimetic targeted against a conserved region in the receptor-binding domain of the Spike. TriSb92 potently neutralizes SARS-CoV-2 and its variants of concern, including Delta and Omicron. Intranasal administration of a modest dose of TriSb92 (5 or 50 micrograms) as early as eight hours before the challenge with SARS-CoV-2 B.1.351 efficiently protected mice from infection. The target epitope of TriSb92 was defined by cryo-EM, which revealed triggering of a conformational shift in the Spike trimer rather than competition for ACE2 binding as the molecular basis of its strong inhibitory action. Our results highlight the potential of intranasal inhibitors in protecting susceptible individuals from SARS-CoV-2 infection, and describe a novel type of inhibitor that could be of use in addressing the challenge posed by the Omicron variant.

The role of contact tracing in COVID-19

Case-based interventions such as case isolation or contact tracing with quarantine have been crucial in controlling the ongoing COVID-19 pandemic, while reducing the need for indiscriminate contact reductions with high economic cost1,2.

Contact tracing aims to identify and interrupt transmission chains by isolating infected patients and quarantining those at risk from infection. More infections are prevented, and epidemic control is improved, if the identification of patients and contacts at risk is rapid and comprehensive3–6. It has been a staple public health intervention in a variety of infectious diseases, notably sexually transmitted diseases and tuberculosis7,8.

Worldwide investments in contact tracing programs and research on the topic have not prevented repeated resurgence of community transmission of COVID-19, underscoring the urgent need for improved knowledge on the effective implementation of this key public health measure6,9.

Forward contact tracing

Forward contact tracing of an index case (the person diagnosed with COVID-19 undergoing contact tracing) intends to interrupt onward transmission from child cases (persons infected by the index case) by quarantining and/or testing contacts the index case has encountered during their infectious period10–12. In the light of substantial asymptomatic and pre-symptomatic transmission, the infectious period is generally assumed to start 2 days prior to onset of symptoms or diagnosis, whichever came first13–18. In addition to child cases, any practical forward tracing strategy probably identifies the parent case (the infector of the index case) and sibling cases (infected by the same parent case) some of the time, for example if the index case had repeated contact with their parent or sibling case during their own infectious period, or if the time from the index case’s infection to their symptom onset or diagnosis was less than two days12. Forward contact tracing is the focus in most jurisdictions and has shown its ability to decrease COVID-19 transmission (Fig. 1)13,14,19.

Backward contact tracing

Backward contact tracing, or bidirectional contact tracing, which combines both approaches, specifically aims to identify the parent case and sibling cases by going back further in time5,10−12. In any practical implementation, additional child cases may also be identified through backward contact tracing, for example if the index case’s infectiousness started more than two days before symptom onset12.

Backward contact tracing is particularly promising in COVID-19 because a small proportion of index cases, the so-called superspreaders, generate the majority of secondary infections11,20−27. This phenomenon favours allocating resources to the identification of source cases and events, as a high rate of infection can be expected amongst individuals exposed to the same source. Endo et al estimate bidirectional contact tracing to result in 2–3 times the number of subsequent cases averted compared to forward contact tracing alone in a simple branching model for COVID-1910. Kojaku et al show backward contact tracing to be highly effective in terms of the number of prevented cases per quarantine when running an SEIR (Susceptible-Exposed-Infectious-Removed) model on synthetic and empirical contact networks, even if contact tracing comprehensiveness is low11.

One potential difficulty of backward contact tracing lies in the inherent delays involved in testing, tracing and quarantine – where infected contacts who are sibling or parent cases risk being detected after or near to the end of their infectious period3,18. This could reduce efficiency and increase the relative cost of testing and quarantine (Fig. 1). Due to these delays, immediate testing of identified contacts in support of iterative tracing may be especially relevant in backward contact tracing.

Types of backward contact tracing

The real-world implementation of backward contact tracing can be broadly subdivided into a source event approach and an extended contact tracing window approach (Fig. 2).

Several countries have rolled out an approach focusing on source events, which are events where the index case is suspected to have contracted COVID-19. The identification of such an event leads to the screening of attendants at risk, which usually includes more individuals than the direct contacts of the index case under investigation28–32. This is because the risk at these events is not related to the index case, but to an unknown parent case. High positivity rates have been reported for attendants of some source events33. In practice, this approach is usually reliant on the identification of multiple confirmed or probable infected cases at the same event, for example by pooling of contact tracing data from different index cases or asking the index case about other cases in their environment. As a result, the approach can fail to identify the source event at the time of identification of the initial index case.

Another approach is to extend the contact tracing window back in time and to systematically refer all close contacts for quarantine and/or testing (Fig. 1, 2). This assumes that, if the tracing window is extended backward by at least the incubation period of the index case, the parent case can be identified, as well as sibling cases present at a shared source event. To this end, the contact tracing window should be extended far enough to include most of the variability in incubation periods34.

Several modelling studies underscore the benefits of extending the contact tracing window for COVID-19. Bradshaw et al show in a stochastic branching-process model that extending the contact tracing window from 2 to 6 days before onset or diagnoses improves the reduction in the effective reproduction number by 85%-275% when using manual contact tracing only (performed by humans rather than through digital means)12. Their findings are robust to contextual factors such as case ascertainment rate, test sensitivity, basic reproduction number and the percentages of asymptomatic, pre-symptomatic and environmental transmission. Fyles et al also show in a branching process model that an extended contact tracing window results in a linear decrease in the growth rate up until around 8 to 10 days prior to symptom onset or diagnosis, although additional gains are highly reliant on recall decay5.

Hypothesis and research question

Whilst there is evidence from modelling studies pointing at the potential benefits of backward contact tracing, no study has evaluated the efficiency in practice. The positivity rate of screened contacts has been proposed as an indicator for efficient allocation of testing and quarantine35,36. In this cohort study we thus determined the positivity rate of additional close contacts (for the purpose of this article this includes co-attendants of high risk events of up to 20 persons) identified in an extended contact tracing window, starting 7 days before onset of symptoms or diagnosis, whichever was earlier. This window was chosen to include the source event most of the time 32–34. We tested the hypothesis that the positivity rate amongst additional contacts in the extended tracing window would be at least as high as amongst a control group of patients attending the test centre for symptoms suggestive of COVID-19. In a first subgroup analysis, we explored how far back the contact tracing window should extend, by calculating the positivity rate of identified contacts grouped by day of last exposure. Our second hypothesis was that the risk would not be limited to possible source events identified at the time of the tracing interview. Therefore, the second subgroup analysis compared our strategy to a source investigation approach, by subgrouping contacts last exposed in the extended contact tracing window according to presence at suspected source events.

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