Thread by @iheartkidneys

1/ Patients who are currently taking ACEi or ARBs are advised not to change their therapy unless directed by their doctor. There is increasing conversation about the interaction of ACE2 and COVID-19. #COVID19 #NephJC #nephtwitter #medtwitter

2/ Let’s talk about current evidence in an effort to decrease confusion about this topic. Check out this amazing post @NephJC for more information by @Nephro_Sparks and @hswapnil nephjc.com/news/covidace2

3/ Angiotensin converting enzyme (ACE) is an important regulator of Renin-Angiotensin-System (RAS). ACE2 is a homolog of ACE, which converts angiotensin (Ang) I to Ang 1-9. Image source: ncbi.nlm.nih.gov/pmc/articles/P…

4/ Why is there so much talk about ACE2 and coronavirus? The link between coronavirus and ACE2 is that the virus gains entry into the cell via ACE2 and type II transmembrane serine proteases (TMPRSS2). 🤯

5/ So does this mean we can alter the entry of coronavirus by altering ACE2 activity? Well, that’s complicated. It has been shown in animal models that both ACE inhibitors and angiotensin receptor blockers can upregulate ACE2 in the heart.

6/ One can then speculate that perhaps this upregulation of ACE2 can also occur in other organs (lungs, kidneys) and lead to increased virus entry leading to infection from coronavirus. However, there is no data to support this one way or the other - at this time.

7/ However, in a study published at EP Europace, Walters et al did not find any association in circulating ACE2 levels with the use of ACE-i or ARBs.
academic.oup.com/europace/artic…

8/ Can ACE-i or ARBs be beneficial in coronavirus and other viral pneumonia?

9/ In a retrospective study by Henry et al, 1055 patients with viral pneumonia were reviewed and they demonstrated an association with improved outcomes in patients with continued ACEi use during the episode of viral pneumonia.
ncbi.nlm.nih.gov/pmc/articles/P…

10/ A paper from 2005 in Nature Medicine suggested that ACE2 is essential to coronavirus infection and its associated lung injury. Decreased ACE2 and normal ACE levels are seen in lungs of mice infected with SARS-CoV.
nature.com/articles/nm1267

11/ A study, looking at both mice and human (pediatric) patients, demonstrated that administration of recombinant ACE2 protein alleviated the severity of lung injury with RSV infection.
nature.com/articles/srep1…

12/ So what about patients with hypertension on ACEi/ARB? What should we do about these medications - in patients with COVID19?

13/ We do not have a prospective study yet to look at the association of #COVID19 incidence in patients with and without hypertension.

14/ Are patients with hypertension more likely to get serious COVID19 or die? Amongst the patients with COVID19, it seems the prevalence of prior history of HTN is higher in those who develop severe disease than those who do not. Same applies for development of ARDS or death.

15/ From the table above, Zhou et al study contains an adjusted analysis for age and other factors, which does NOT show an association between hypertension and age. thelancet.com/journals/lance…

16/ Hypertension does seem to be a common comorbidity, even more so than diabetes - but these are all data from one country, so one should be careful before generalization.

17/ What is the take away from all this - as it stands right now? Unfortunately, it is not clear whether or not continuing or stopping ARBs or ACEi is warranted in #COVID19. However, it is clear that ACE2 and TMPRSS2 are important targets for therapy.

18/ Patients who are taking ACEi or ARBs for hypertension are not advised to change their therapy unless there are other reasons to stop them - such as AKI, hyperkalemia, hypotension. Here is a statement from European Society of Cardiology (ESC):

19/ Don’t forget to follow nephjc.com/covid19 and nephjc.com/news/covidace2 for updated information on this topic. @NephJC @Nephro_Sparks @hswapnil #COVID19