COVID 19, Angiotensin Receptor Blockers, and the Brain
and Recommendations 1. Well regarded clinical studies demonstrate that the SARS CoV 2 virus affects the function of many organs besides the lung, including the brain. Neurological examinations are needed for all patients infected with SARS CoA 2, whether symptomatic for COVID 19 or not, and certainly during hospitalization. COVID 19 patients should be considered a group at higher risk for brain disorders, even after recovery from the disease. Long term neurologic follow up after recovery from COVID 19 will reveal whether this illness is associated with neurodegenerative conditions susceptible of early treatment. Mental health support should be offered to COVID 19 patients and their families after recovery from the critical stage of their illness. 2. It has been conclusively demonstrated that treatment with ARBs protects patients and ameliorates the consequences of cerebral, cardiovascular, metabolic, and renal disorders that later become frequent COVID 19 comorbidities. ARBs have been shown to protect lung function, reduce the severity of pneumonia, and alleviate chronic pulmonary disease. These findings strongly support not to discontinue ARB treatment when medically prescribed. Abrupt ARB withdrawal in these patients will expose them to a significant risk of serious complications. 3. To definitely answer the recommendations to withdraw ARB treatment from patients already medicated with ARBs for cardiovascular and other disorders, we would need additional studies, many of them already under way. First, we need clear and conclusive evidence that ARB treatment does not predispose patients to SARSCoV 2 infection. Are patients under ARB treatment less likely to be infected with SARS CoV 2? To answer this question, we would need population studies and data analysis to establish that the patient population treated with ARBs is not at higher, but instead at lower risk of SARS CoV 2 infection. Furthermore, are patients infected with SARS CoV 2 more likely to be asymptomatic if they have been previously treated with ARBs? The answers to these questions will require clinical studies and data analysis not presently under consideration. 4. At present, even more pressing studies are under way to determine the effect of previous ARB treatment that has been continued during hospitalization of COVID 19 patients. The presence or absence of ARB therapy in COVID 19 patients is now carefully documented and monitored in many clinical centers, including determination of ARB protection against COVID 19 induced hypertension. We need to conclusively determine whether continuation of ARB treatment in COVID19 non hospitalized or hospitalized patients is beneficial, reducing progression, accelerating recovery, and decreasing mortality. Several preliminary analyses demonstrate that ARBs reduce the severity and mortality of COVID 19 patients (see details in the text) and more definitive results are likely to be published momentarily. These data analysis will also discover whether discontinuation of ARB therapy prior to COVID 19 diagnosis influences the progression of the disease. 671 Cellular and Molecular Neurobiology (2020) 40:667 674 1 3 5. A most important question remaining is whether de novo ARB administration to COVID 19 patients could be therapeutically efficacious. There are at present (0428 2020) at least 24 new carefully designed controlled clinical trials looking at de novo ARB administration to COVID 19 patients testing this hypothesis and including the effects of discontinuation of ARB therapy in COVID 19 patients. https /clini caltr ials.gov/ct2/ resul ts?cond=COVID 19&term=angio tensi n+recep tor+block ers&cntry &state &city=&dist= 6. While clinical studies as the ones described above are of immediate value, experimental research will be needed to clarify the effects of ARBs on SARS CoV 2 entry into the cells and its virulence, and to establish the effects of ARBs not only on ACE2 but also on other coronavirus co receptors and on associated signal transduction mechanisms.
Cellular and Molecular Neurobiology