Increased Incidence, Morbidity, and Mortality in Human Coronavirus NL63 Associated with ACE Inhibitor Therapy and Implication in SARS-CoV-2 (COVID-19)

Background The endemic human coronavirus NL63 strain (HCoVNL63) employs angiotensinconverting enzyme 2 (ACE-2) receptors on cell surfaces to infect hosts in the same manner as SARS-CoV and the novel SARSCoV-2. It has been proposed that patients on angiotensinconverting enzyme inhibitor (ACE-I) and angiotensin receptor blockers (ARB) therapy infected with SARS-CoV-2 have a higher mortality rate due to overexpression of ACE-2 receptors. Aim We sought to evaluate the impact of ACE-I/ARB on infectivity of various endemic coronavirus strains, hypothesizing that rates of ACE-I use among patients with HCoVNL63 would be higher compared to other endemic coronavirus strains that do not utilize the ACE-2 receptor. Design/Methods A retrospective cohort study was designed to evaluate a total 466 subjects with a positive respiratory pathogens panel for one of the endemic coronavirus strains. Rate of ACE-I/ARB use among each coronavirus strain and clinical outcomes from the 88 HCoV-NL63 positive subjects was collected. Results Analysis revealed a higher rate of ACE-I (p=0.006) use among the HCoV-NL63 positives compared to the other three endemic coronavirus strains. The rate of invasive mechanical ventilation (p=0.007) and 90day mortality (p=0.045) among HCoV-NL63 positives on ACE-I therapy was higher compared to those HCoV-NL63 positives not on ACE-I therapy. Conclusion Concurrent therapy with an ACE-I was associated with an increased rate and severity of infection with the HCoV-NL63. This association was not found in infected patients on concurrent ARB therapy. These findings support the importance of further evaluation in patients on these therapies who are infected with the novel coronavirus SARSCoV-2.

Salivary and serum IgA and IgG responses to SARS-CoV-2-spike protein following SARS-CoV-2 infection and after immunization with COVID-19 vaccines.

Background: Secretory immunoglobulin A (sIgA) plays an important role in antiviral protective immunity. Although salivary testing has been used for many viral infections, including severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), its use has not yet been well established with the SARS coronavirus 2 (SARS-CoV-2). Quantification of salivary IgA and IgG antibodies can elucidate mucosal and systemic immune responses after natural infection or vaccination. Here, we report the development and validation of a rapid enzyme-linked immunosorbent assay (ELISA) for anti-SARS-CoV-2 salivary IgA and serum IgG antibodies, and present quantitative results for immunized subjects both prior to or following COVID-19 infections. Objective: Total and serum SARS-CoV-2 spike-specific IgG responses were compared with salivary spike-specific IgA and IgG responses in samples obtained from patients recently infected with SARS-CoV-2 and from subjects recently immunized with COVID-19 vaccines. Methods: A total of 52 paired saliva and serum samples were collected from 26 study participants: 7 subjects after COVID-19 infection and 19 subjects who were uninfected. The ELISA results from these samples were compared with five prepandemic control serum samples. Total IgG and SARS-CoV-2 spike-specific IgG in the serum samples from the subjects who were infected and vaccinated were also measured in a commercial laboratory with an enzyme immunoassay. Results: A wide variation in antibody responses was seen in salivary and serum samples measured by both methods. Three groups of serum total and IgG spike-specific SARS-CoV-2 antibody responses were observed: (1) low, (2) intermediate, and (3) high antibody responders. A correlational analysis of salivary IgA (sIgA) responses with serum IgG concentrations showed a statistical correlation in the low and intermediate antibody responder groups but not in the high group (which we believe was a result of saturation). Conclusion: These preliminary findings suggest measuring salivary and serum IgG and IgA merit further investigation as markers of current or recent SARS-CoV-2 infections.

Increased Incidence, Morbidity, and Mortality in Human Coronavirus NL63 Associated with ACE Inhibitor Therapy and Implication in SARS-CoV-2 (COVID-19)

BACKGROUND: The endemic human coronavirus NL63 strain (HCoV-NL63) employs angiotensin-converting enzyme 2 (ACE-2) receptors on cell surfaces to infect hosts in the same manner as SARS-CoV and the novel SARS-CoV-2. It has been proposed that patients on angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blockers (ARB) therapy infected with SARS-CoV-2 have a higher mortality rate due to over-expression of ACE-2 receptors. AIM: We sought to evaluate the impact of ACE-I/ARB on infectivity of various endemic coronavirus strains, hypothesizing that rates of ACE-I use among patients with HCoV-NL63 would be higher compared to other endemic coronavirus strains that do not utilize the ACE-2 receptor. DESIGN/METHODS: A retrospective cohort study was designed to evaluate a total 466 subjects with a positive respiratory pathogens panel for one of the endemic coronavirus strains. Rate of ACE-I/ARB use among each coronavirus strain and clinical outcomes from the 88 HCoV-NL63 positive subjects was collected. RESULTS: Analysis revealed a higher rate of ACE-I (p=0.006) use among the HCoV-NL63 positives compared to the other three endemic coronavirus strains. The rate of invasive mechanical ventilation (p=0.007) and 90-day mortality (p=0.045) among HCoV-NL63 positives on ACE-I therapy was higher compared to those HCoV-NL63 positives not on ACE-I therapy. CONCLUSION: Concurrent therapy with an ACE-I was associated with an increased rate and severity of infection with the HCoV-NL63. This association was not found in infected patients on concurrent ARB therapy. These findings support the importance of further evaluation in patients on these therapies who are infected with the novel coronavirus SARS-CoV-2.