Perspective: the nose and the stomach play a critical role in the NZACE2-Pātari* (modified ACE2) drug treatment project of SARS-CoV-2 infection

Ameratunga, Rohan; Woon, See Tarn; Steele, Richard; Snell, Russell G.; Medlicott, Natalie J.; Mears, Emily; Leung, Euphemia; Lehnert, Klaus; Jordan, A. M.; Das, Shyamal C.; Abbott, William G.H.; Longhurst, Hilary; Quiñones‐Mateu, Miguel E.

doi:10.1080/1744666x.2021.1912596

Cited by 11 publications

(8 citation statements)

References 67 publications

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“…99 NZACE2-P atari will be administered on several occasions over 2 days by a nasal dropper at the onset of infection. 99 The NZACE2-P atari/SARS-CoV-2 complexes would be swallowed, leading to hydrolytic destruction of the virus in the stomach. If proven safe and effective in clinical trials, this treatment would be particularly attractive for CVID patients who have poor T-cell responses to COVID-19 vaccines.…”

Section: Assessing the Immune Response To Covid-19 Vaccinesmentioning

confidence: 99%

Common Variable Immunodeficiency Disorders, T-Cell Responses to SARS-CoV-2 Vaccines, and the Risk of Chronic COVID-19

Ameratunga

Longhurst

Steele

et al. 2021

The Journal of Allergy and Clinical Immunology: In Practice

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COVID-19 has had a calamitous effect on the global community. In spite of intense study, the immunological response to the infection is only partially understood. In addition to older age and ethnicity, patients with co-morbidities including obesity, diabetes, hypertension, coronary artery disease, malignancy, renal and pulmonary disease, may experience severe outcomes. Some patients with primary and secondary immunodeficiencies also appear to be at increased risk from COVID-19. In addition to their vulnerability to SARS-CoV-2, patients with primary immunodeficiencies (PIDs) often suffer from chronic pulmonary disease and may not respond to vaccines, exacerbating their long-term risks. Patients with Common Variable Immunodeficiency disorders (CVID), the most frequent symptomatic PID in adults and children, have a spectrum of B and T cell defects. It may be possible to stratify their risk of severe COVID-19 based on age, ethnicity, the severity of their T cell defect as well as the presence of other co-morbidities. Patients with CVID and other immunodeficiencies are at risk of chronic COVID-19, a dangerous stalemate between a suboptimal immune response and SARS-CoV-2. Intra-host viral evolution could result in the rapid emergence of vaccine resistant mutants and is a public health emergency. Vaccination and prevention of Chronic COVID-19 in immunodeficient patients is therefore of the highest priority. Having a reliable diagnostic assay for T cell immunity to SARS-CoV-2 is critical for evaluating responses to vaccines in these patients. New treatments such as NZACE2-Pātari for COVID-19, are likely to be of particular benefit to immunodeficient patients, especially those who fail to mount a robust T cell response to vaccines.

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Section: Assessing the Immune Response To Covid-19 Vaccinesmentioning

confidence: 99%

Common Variable Immunodeficiency Disorders, T-Cell Responses to SARS-CoV-2 Vaccines, and the Risk of Chronic COVID-19

Ameratunga

Longhurst

Steele

et al. 2021

The Journal of Allergy and Clinical Immunology: In Practice

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“…SARS-CoV-2 deploys several mechanisms to evade cytoplasmic viral sensors. Following the nasal phase, the virus infects the lungs, probably by microaspiration from the nasopharynx and stomach ( 5 , 6 ). Patients suffering pneumonitis experience increasing dyspnoea and have elevated inflammatory markers.…”

Section: Introductionmentioning

confidence: 99%

Common Variable Immunodeficiency Disorders as a Model for Assessing COVID-19 Vaccine Responses in Immunocompromised Patients

et al. 2022

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“…Given the propensity for rapid viral evolution, one option has been to intercept and block SARS-CoV-2 in the nasal phase of the infection [ 124 , 125 ]. The NZACE2-Pātari project proposes using modified ACE2 molecules (N90D/R273A) to bind the virus early in the nasal phase to mitigate the pulmonary and systemic phases.…”

Section: Limited Therapeutic and Protective Role Of Sars-cov-2 Antibo...mentioning

confidence: 99%

“…It has been noted in multiple studies that patients prescribed proton pump inhibitors (PPIs) are at increased risk of severe disease [ 127 ]. The stomach may serve as a reservoir for intact SARS-CoV-2 and be aspirated to the lungs [ 125 ]. Data from China showed exposure to a higher viral inoculum was associated with a risk of death even in younger HCWs, before the use of personal protective equipment.…”

Section: Emerging Explanations For the (Apparent) Antibody Paradox In...mentioning

confidence: 99%

The (apparent) antibody paradox in COVID-19

Ameratunga

Woon

Lea

et al. 2022

Expert Review of Clinical Immunology

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Introduction The immunological response to COVID-19 is only partly understood. It is increasingly clear that the virus triggers an inappropriate host inflammatory reaction in patients experiencing severe disease. Areas covered The role of antibodies in COVID-19 remains to be fully defined. There is evidence for both protection and harm in different clinical syndromes triggered by SARS-CoV-2. Many patients dying from COVID-19 had both high titers of antibodies to SARS-CoV-2 and elevated viral loads. The uncertain protective role of humoral immunity is mirrored by the lack of benefit of therapeutic convalescent plasma infusions in COVID-19. In contrast, there is increasing evidence that a vigorous T-cell response is protective. Delayed or low avidity T cell reactions were seen in patients suffering severe COVID-19. Expert opinion These observations suggest T cell responses to SARS-CoV-2 are the dominant long-term protective mechanism following either infection or vaccination. The magnitude and quality of the antibody response is likely to reflect underlying T cell immunity to SARS-CoV-2. Much of what has been learned about COVID-19 will need to be revised following the recent rapid emergence and dominance of the omicron variant of SARS-CoV-2.

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Perspective: the nose and the stomach play a critical role in the NZACE2-Pātari* (modified ACE2) drug treatment project of SARS-CoV-2 infection

Cited by 11 publications

References 67 publications

Common Variable Immunodeficiency Disorders, T-Cell Responses to SARS-CoV-2 Vaccines, and the Risk of Chronic COVID-19

Common Variable Immunodeficiency Disorders, T-Cell Responses to SARS-CoV-2 Vaccines, and the Risk of Chronic COVID-19

Common Variable Immunodeficiency Disorders as a Model for Assessing COVID-19 Vaccine Responses in Immunocompromised Patients

The (apparent) antibody paradox in COVID-19

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