We thank Rothlin and colleagues for their comments on our work1 regarding the contribution of the angiotensin pathway to COVID-19 clinical manifestations. It is important that the therapeutic potential of AT1 receptor blockers (ARBs) in COVID-19 is fully discussed and that these drugs should be seen as a therapeutic opportunity and not as a threat.

We agree that telmisartan has pharmacokinetic and pharmacodynamic profiles that make this ARB particularly suitable for use in COVID-19. Telmisartan exerts an insurmountable and reversible inhibition of angiotensin II-induced responses2 with an AT1 blockade that is more resistant even to very large increases in angiotensin II concentrations in the receptor biophase, as expected to occur in the lungs during COVID-19. Telmisartan also offers the advantage of having its safety established at higher doses than those commonly used as an antihypertensive (up to 160mg)2 and during a period that fits the time needed for COVID-19 treatment.

Rothlin and colleagues highlighted the fact that telmisartan has additional anti-inflammatory effects that are superior to other ARBs, based on its unique direct activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ). As we mentioned in a previous comment,3 we have doubts about the relevance of PPAR-γ activation due to the fact the concentrations needed for such activation would be reached only during telmisartan's steady state Cmax.4,5 Therefore, any contribution of PPAR-γ activation to the expected anti-inflammatory response elicited by telmisartan should be minimal, compared to the expected anti-inflammatory response caused by blockade of AT1 receptor activation.6–8 Our hypothesis is that dose is the key factor. The marginal benefits of ARBs and angiotensin-converting enzyme inhibitors in protecting patients suffering from COVID-19 seen in some meta-analyses1,9 are probably associated with the use of these drugs at antihypertensive doses. Despite our position in favor of telmisartan as a first choice, we do not support its uniqueness for COVID-19 treatment. We consider, however, the need to use the highest possible dose as a major requirement for the contribution of any ARB to COVID-19 treatment.