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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease of 2019 (COVID-19), has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorized for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to the deaths of some fully vaccinated persons. Others with normal immunity may have chosen not to be vaccinated and remain at risk if they contract the infection. Vaccines may not protect some immunodeficient patients from SARS-CoV-2, who are also at increased risk of chronic COVID-19 infection, a dangerous stalemate between the virus and a suboptimal immune response. Intra-host viral evolution could rapidly lead to the selection and dominance of vaccine and monoclonal antibody-resistant clades of SARS-CoV-2. There is thus an urgent need to develop new treatments for COVID-19. The NZACE2-Pātari project, comprising modified soluble angiotensin-converting enzyme 2 (ACE2) molecules, seeks to intercept and block SARS-CoV-2 infection of the respiratory mucosa. In vitro data presented here show that soluble wild-type ACE2 molecules retain the ability to effectively block the Spike (S) glycoprotein of SARS-CoV-2 variants including the ancestral Wuhan, delta (B.1.617.2) and omicron (B.1.1.529) strains. This therapeutic strategy may prove effective if implemented early during the nasal phase of the infection and may act synergistically with other antiviral drugs such as Paxlovid to further mitigate disease severity. This article shows that soluble wild-type ACE2 receptors can block the binding of the SARS-CoV-2 to ACE2. This is an antiviral strategy that is resistant to viral evolution. In the future, it may be used against new variants of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

COVID-19 has caused calamitous health, economic and societal consequences. Although several COVID-19 vaccines have received full authorization for use, global deployment has faced political, financial and logistical challenges. The efficacy of first-generation COVID-19 vaccines is waning and breakthrough infections are allowing ongoing transmission and evolution of SARS-CoV-2. Furthermore, COVID-19 vaccine efficacy relies on a functional immune system. Despite receiving three primary doses and three or more heterologous boosters, some immunocompromised patients may not be adequately protected by COVID-19 vaccines and remain vulnerable to severe disease. The evolution of new SARS-CoV-2 variants has also resulted in the rapid obsolescence of monoclonal antibodies. Convalescent plasma from COVID-19 survivors has produced inconsistent results. New drugs such as Paxlovid (nirmatrelvir/ritonavir) are beyond the reach of low- and middle-income countries. With widespread use of Paxlovid, it is likely nirmatrelvir-resistant clades of SARS-CoV-2 will emerge in the future. There is thus an urgent need for new effective anti-SARS-CoV-2 treatments. The in vitro efficacy of soluble ACE2 against multiple SARS-CoV-2 variants including omicron (B.1.1.529), was recently described using a competitive ELISA assay as a surrogate marker for virus neutralization. This indicates soluble wild-type ACE2 receptors are likely to be resistant to viral evolution. Nasal and inhaled treatment with soluble ACE2 receptors has abrogated severe disease in animal models of COVID-19. There is an urgent need for clinical trials of this new class of antiviral therapeutics, which could complement vaccines and Paxlovid. • After intense study the correlates of protective immunity to SARS-CoV-2 are now better understood. • Although several COVID-19 vaccines have received full authorization for use, they do not prevent breakthrough infection although disease severity is mitigated in fully-immunized individuals. • There is a dearth effective antiviral therapeutics for SARS-CoV-2: Repurposing existing drugs for COVID-19 has been disappointing. While effective, Paxlovid is beyond the reach of most low- and middle-income countries. • A recent in vitro study showed that the ancestral Wuhan and newer SARS-CoV-2 variants including delta (B.1.617.2) and omicron (B.1.1.529) are inhibited by soluble ACE2 receptors. • Mucosal treatment of SARS-CoV-2 with soluble ACE2 receptors may represent an effective strategy to mitigate COVID-19 and may complement current vaccines and drugs including Paxlovid. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has caused calamitous health, economic and societal consequences globally. Currently, there is no effective treatment for the infection. Areas covered: We have recently described the NZACE2-Pātari project, which seeks to administer modified Angiotensin Converting Enzyme 2 (ACE2) molecules early in the infection to intercept and block SARS-CoV-2 binding to the pulmonary epithelium. Expert opinion: Since the nasopharyngeal mucosa is infected in the first asymptomatic phase of the infection, treatment of the nose is likely to be safe and potentially effective. The intercepted virus will be swallowed and destroyed in the stomach. There is however a limited window of opportunity to alter the trajectory of the infection in an individual patient, which requires access to rapid testing for SARS-CoV-2. The proposed strategy is analogous to passive immunization of viral infections such as measles and may be of particular benefit to immunodeficient and unvaccinated individuals. [ABSTRACT FROM AUTHOR]

Since most CVID patients are on SCIG/IVIG, a T cell assay is required to demonstrate antecedent infection or responses to COVID-19 vaccines. Keywords: COVID-19; SARS-CoV-2; Tcell assay; thymidine uptake; cellular response EN COVID-19 SARS-CoV-2 Tcell assay thymidine uptake cellular response 1159 1161 3 11/08/21 20211101 NES 211101 B To the editor b Dear Sir, We thank colleagues from Adaptive Biotechnologies for their interest in our paper outlining the urgent need for diagnostic laboratories to develop and offer T cell assays for COVID-19 [[1]]. A T cell assay may also be very helpful in identifying antecedent COVID-19 in patients presenting with a variety of clinical scenarios such as pulmonary fibrosis or myocarditis but with negative SARS-CoV-2 tests [[1]]. [Extracted from the article]