ACE2, ACE, DPPIV, PREP and CAT L enzymatic activities in COVID-19: imbalance of ACE2/ACE ratio and potential RAS dysregulation in severe cases (preprint)

Objective and design: Several proteases have drawn attention as potential targets to control the SARS-CoV-2 infection (COVID-19), thus circulating enzymatic activity and RAS regulation in severe hospitalized patients still remain to be determined. Material or subjects: 164 patients with COVID-19-like symptoms were grouped according to the severity of symptoms (COVID-19 negative, mild, moderate and severe). Methods: Patients were subjected to biochemical analyzes and to enzymatic activities of ACE2, ACE, DPPIV, PREP and CAT L, evaluated in serum samples. One-way ANOVA and multivariate logistic regression analysis were used. Statistical significance was accepted at p<0.05. Results: We show a correlation among comorbidities, elevated C-reactive protein (CRP) levels and disease severity. Additionally, concomitant high levels of D-dimer and CRP could be as prognostic for severe conditions. Assays of enzymatic activities revealed that, according to disease severity, both ACE2 and CAT L were statistically increased, while ACE, DPPIV and PREP activities were significantly reduced. Notably, analysis of ACE2/ACE ratio suggest a possible imbalance of Ang II/Ang1-7 ratio in severe patients. Conclusion: Our findings reveal the correlation between protease activity and the severity of COVID-19, in addition to highlighting the imbalance of ACE2/ACE ratio, predicting RAS dysregulation, closely related with a poor outcome of disease.

Pre-Exposure Prophylaxis During COVID-19 Pandemic: Can PrEP Prevent Flu-Like Symptoms? (preprint)

Background: Considering speculations on an eventual contribution of antiretroviral drugs to treat novel coronavirus, PrEP regular use may provide useful information and clarify its role in preventing flu-like symptoms.Objective: To identify risk and/or protective factors against flu-like symptoms during COVID-19 pandemic among PrEP regular users.Methods: Phone call interview or digital investigation (through WhatsApp® or e-mail) about PrEP regular use during the novel coronavirus pandemic, social distancing, exposure to suspected or confirmed cases of COVID-19 and recent flu-like symptoms.Findings: Among 108 individuals, the majority were cisgender, white, and gay men. Although most of the individuals were in social distancing (68,52%), they did not stop taking PrEP (75,93%). Fewer people had had contact with suspected or confirmed cases of COVID-19 (12,04%), but some did have flu-like symptoms the month before the interview (27,78%) including rhinorrhea (56,67%), cough (53,33%), asthenia (50,00%) and headache (43,33%). Also, PrEP regular use was a protective factor against flu-like symptoms (OR = 0.26, 95% CI 0.07-0.96, p = 0.04) and was associated with social distancing adherence (OR = 7.2, 95% CI 2.74-19.02, p < 0.001).Conclusion: In our sample, regular use of PrEP was a protective factor against flu-like symptoms and was related to the accomplishment of social distancing during the COVID-19 pandemic in São Paulo, Brazil.