Coronavirus

Should I continue or discontinue angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in my patients with possible Coronavirus/Covid-19 infection?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

The original reports of an association between hypertension and increased risk of mortality in hospitalized patients with Covid-19 infection raised concern over the potential deleterious role of ACEIs or ARBs in such patients.1-4 However, as stated by a joint statement of several cardiology societies, including the American Heart Association, American College of Cardiology and the European Society of Cardiology on March 13, 2020, there is no clinical or scientific evidence that ACEI or ARBS should be routinely discontinued in patients with Covid-19 infection.5

In fact, some have argued for the opposite ie, consideration for the use of ARBs, such as losartan (an angiotensin receptor 1 [AT1R] antagonist), in patients with Covid-19.6,7  Although it is true that Covid-19 appears to use ACE2 as a binding site to infect cells (just as in SARS) and that ACE2 may be upregulated in patients on chronic ACEI or ARBs,8,9 ACE2 may also potentially protect against severe lung injury associated with infections.10,11  

Two complementary mechanisms have been posited for the potential protective effect of ARBs in Covid-19 infection-related lung injury: 1. Blocking the excessive AT1R activation caused by the viral infection; and 2. Upregulation of ACE2, thereby reducing production of angiotensin II and increasing the production of the vasodilator angiotensin 1-7.7

In the absence of proper clinical studies, it is premature, however, to recommend use of losartan or other AT1R antagonists as a means of reducing the likelihood of ARDS in patients with Covid-19 at this time.

Bonus Pearl: Did you know that ARDS is a major cause of death in Covid-19 infection?12

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020, March 6. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2002032?articleTools=true
  2. O’Mara GJ. Could ACE inhibitors, and particularly ARBs, increase susceptibility to COVID-19 infection? BMJ 2020;368:m406 ARTICLE
  3. Sommerstein R, Grani C. Preventing a Covid-19 pandemic: ACE inhibitors as a potential risk factor for fatal Covid-19. BMJ2020;368:m810. https://www.bmj.com/content/368/bmj.m810/rr-2
  4. Li X, Geng M, Peng Y, et al. Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis 2020, doi htps://doi.org/10.106/j.jpha.2020.03.001. https://www.sciencedirect.com/science/article/pii/S2095177920302045
  5. Cardiology societies recommend patients taking ACE inhibitors, ARBs who contract COVID-19 should continue treatment. March 17, 2020. https://www.healio.com/cardiology/vascular-medicine/news/online/%7Bfe7f0842-aecb-417b-9ecf-3fe7e0ddd991%7D/cardiology-societies-recommend-patients-taking-ace-inhibitors-arbs-who-contract-covid-19-should-continue-treatment
  6. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res 2020;1-4. https://www.ncbi.nlm.nih.gov/pubmed/32129518/
  7. Phadke M, Saunik S. Response to the emerging novel coronavirus outbreak. BMJ 2020;368:m406. https://www.bmj.com/content/368/bmj.m406/rr-2
  8. Zheng YY, Ma YT, Zhang JY, et al. COVID-19 and the cardiovascular system. Nature Reviews/Cardiology 2020; https://doi.org/10.1038/s41569-020-0360-5 .
  9. Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005;111:2605-2610. https://www.ahajournals.org/doi/full/10.1161/circulationaha.104.510461
  10. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nature Medicine 2005;11:875-79. Doi:10.1038/nm1267 https://www.nature.com/articles/nm1267?v=1
  11. Tikellis C, Thomas MC. Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin angiotensin system in health and disease. International Journal of Peptides. Volume 2012, Article ID 256294, 8 pages. Doi:10.1155/2012/256294. https://research.monash.edu/en/publications/angiotensin-converting-enzyme-2-ace2-is-a-key-modulator-of-the-re

12 . Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020. https://doi.org/10.1016/S0140-6736(20)30183-5

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should I continue or discontinue angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in my patients with possible Coronavirus/Covid-19 infection?

What existing drugs are currently being evaluated or repurposed for treatment of Coronavirus (Covid-19) infection?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

There are currently no drugs specifically approved for treatment of Covid-19 infections. However, there are legions of therapies that are being considered, tried, and/or evaluated in clinical trials. Many experts believe a combination of drugs may be necessary for optimal therapy. Here is my select list of potentially promising drugs from gleaning the literature and online resources to date.1-16

  • Remdisivir: A broad spectrum investigational nucleoside analogue, originally developed to treat a variety of viruses, including Ebola, SARS and MERS. Active in vitro against Covid-19. Favorable results have been reported in some cases, including the first reported patient in the U.S.
  • Chloroquine: An old drug used for its antimalarial activity as well as for its immune modulation and anti-inflammatory properties. Has also been found to be active in mice against a variety of viruses, including certain enteroviruses, Zika virus, influenza A H5N1.  Active in vitro against Covid-19, though hydroxychloroquine may be more effective. Evidence for its efficacy in treating acute viral infections in humans is currently lacking.
  • Lopinavir/ritonavir: Protease inhibitor combo used in HIV infection with possibly some benefit in the treatment of SARS. Recent study showed no significant efficacy in severe Covid-19 disease. 
  • Interferon-alpha: An antiviral cytokine used against hepatitis B and C viruses. May be more effective for prophylaxis than post-exposure, based on experimental animal studies involving SARS.
  • Ribavirin: Another nucleoside analogue approved for hepatitis C (in combination with other drugs) and respiratory syncytial virus (RSV) infections but also evaluated in SARS and MERS. Has been reported to be active in vitro against Covid-19.
  • Sofosbuvir: Inhibits RNA-dependent RNA polymerase. Approved for treatment of hepatitis C, but also with in vitro activity against Covid-19.
  • Tocilizumab: Anti-interleukin-6 monoclonal antibody used in rheumatoid and giant cell arthritis. Theoretically, may mitigate cytokine storm observed in some patients during the later stages of Covid-19 disease.

Of course, there are many more drugs some of which would not be expected to be effective against Covid-19, based on what we so far know this virus. These include darunavir/cobicistat, oseltamivir, immunoglobulins, arbidol (an antiviral used in Russia and China vs influenza), angiotensin receptor blockers, stem cell therapy, convalescent plasma, and traditional Chinese medicine.

Remember corticosteroids are currently not recommended in the absence of other indications for their use (see related PEARL).

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. US National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=2019nCoV&term=&cntry=&state=&city=&dist
  2. Li Guangdi, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature Reviews Drug Discovery 2020; Feb 19, 2010. https://www.nature.com/articles/d41573-020-00016-0
  3. Harrison C. Coronavirus puts drug repurposing on the fast track. Nature Biotechnology 020, Feb 27. https://www.nature.com/articles/d41587-020-00003-1
  4. Velavan TP, Meyer CG. The COVID-19 epidemic. Tropical Medicine and International Health 2020;25:278-280. https://onlinelibrary.wiley.com/doi/full/10.1111/tmi.13383
  5. Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sciences 2020;248. 11747. https://www.sciencedirect.com/science/article/pii/S0024320520302253
  6. Wang Y, Wang Y, Chen Y, et al. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol 2020;March 5. https://www.ncbi.nlm.nih.gov/pubmed/32134116
  7. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2029 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. https://www.ncbi.nlm.nih.gov/pubmed/31986264
  8. Paules CI, Marston HD, Fauci AS. Coronavirus infections—More than just the common cold. JAMA 2020;323:707-78. https://jamanetwork.com/journals/jama/fullarticle/2759815
  9. Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Research 2020;177. 104762. https://www.sciencedirect.com/science/article/pii/S0166354220301145
  10. Gurwitz D. Angiotensin receptor blockers as tentavie SARS-CoV-2 therapeutics. https://www.ncbi.nlm.nih.gov/pubmed/32129518/
  11. Wang M, Cao R, Zhang L, et al. Remdesivir and chlorquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research 2020;30:269-71. https://www.nature.com/articles/s41422-020-0282-0
  12. Roques P, Thiberville SD, Dupuis-Maguirara L, et al. Paradoxical effect of chloroquine treatment in enhancing Chikungunya virus infection. Viruses 2018;10, 268. https://www.ncbi.nlm.nih.gov/pubmed/29772762
  13. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 2020;March 3. https://jamanetwork.com/journals/jama/fullarticle/2762688
  14. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020; March 5. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
  15. Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020. March 9. https://www.ncbi.nlm.nih.gov/pubmed?term=32150618
  16. Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl M Med 2020, March18. DOI:10.1056/NEJMoa2001282. https://www.nejm.org/doi/full/10.1056/NEJMoa2001282

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What existing drugs are currently being evaluated or repurposed for treatment of Coronavirus (Covid-19) infection?

Key clinical pearls in the medical management of hospitalized patients with coronavirus (Covid-19) infection

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , 1 Comment

First, a shout-out to dedicated healthcare workers everywhere who have selflessly given of themselves to care for the sick during this pandemic. Thank you! Together, I know we will get through it!

Although our understanding of Covid-19 infection is far from complete, in the spirit of clarity and brevity of my posts on Pearls4Peers, here are some key points I have gleaned from review of existing literature and the CDC that may be useful as we care for our hospitalized patients with suspected or confirmed Covid-19 infection.

  • Isolation precautions.1 Per CDC, follow a combination of airborne (particularly when aerosol generating procedures is anticipated, including nebulizer treatment) and contact precaution protocols. Routinely use masks or respirators, such as N-95s (subject to local availability and policy) and eye protection. Don gowns (subject to local availability and policy) and gloves and adhere to strict hand hygiene practices.

 

  • Diagnostic tests1-9
    • Laboratory tests. Routine admission labs include CBC, electrolytes, coagulation panels and liver and renal tests. Other frequently reported labs include LDH, C-reactive protein (CRP) and procalcitonin. Testing for high sensitivity troponin I has also been performed in some patients, presumably due to concern over ischemic cardiac injury or myocarditis.2 Check other labs as clinically indicated.
    • Chest radiograph/CT chest. One or both have been obtained in virtually all reported cases with CT having higher sensitivity for detection of lung abnormalities.
    • EKG. Frequency of checking EKGs not reported in many published reports thought 1 study reported “acute cardiac injury” in some patients, based in part on EKG findings.4 Suspect we will be checking EKGs in many patients, particularly those who are older or are at risk of heart disease.
    • Point-of-care ultrasound (POCUS). This relatively new technology appears promising in Covid-19 infections, including in rapid assessment of the severity of pneumonia or ARDS at presentation and tracking the evolution of the disease. 9 Don’t forget to disinfect the probe between uses!

 

  • Treatment 1-8
    • Specific therapies are not currently available for treatment of Covid-19 infections, but studies are underway.
    • Supportive care includes IV fluids, 02 supplementation and nutrition, as needed. Plenty of emotional support for patients and their families will likely be needed during these times.
    • Antibiotics have been used in the majority of reported cases, either on admission or during hospitalization when superimposed bacterial pneumonia or sepsis could not be excluded.
      • Prescribe antibiotics against common community-acquired pneumonia (CAP) pathogens, including those associated with post-viral/influenza pneumonia such as Streptococcus pneumoniae (eg, ceftriaxone), and Staphylococcus aureus (eg, vancomycin or linezolid if MRSA is suspected) when concurrent CAP is suspected.
      • Prescribe antibiotics against common hospital-acquired pneumonia (HAP) (eg, vancomycin plus cefepime) when HAP is suspected.
    • Corticosteroids should be avoided because of the potential for prolonging viral replication, unless indicated for other reasons such as COPD exacerbation or septic shock. 1
    • Monitor for deterioration in clinical status even when your hospitalized patient has relatively minor symptoms. This is because progression to lower respiratory tract disease due to Covid-19 often develops during the 2nd week of illness (average 9 days).
    • ICU transfer may be necessary in up to 30% of hospitalized patients due to complications such as ARDS, secondary infections, and multi-organ failure.

 

Again, thank you for caring for the sick and be safe! Feel free to leave comments or questions.

 

 Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References

  1. CDC. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html
  2. Ruan Q, Yang K, Wang W, Jiang L, et al. Clinical predictors of mortality due to COVID-19 based on analysis of data of 150 patients with Wuhan, China. Intensive Care Med 2020. https://link.springer.com/article/10.1007/s00134-020-05991-x
  3. Holshue ML, BeBohlt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929-36. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
  4. Huang C, Wang Y, Li Xingwang, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)30183-5.pdf
  5. Young BE, Ong SWX, Kalimuddin S, et al. Epideomiologic features and clinical course of patients infected with SARS-CoV-2 Singapore. JAMA, March 3, 2020. Doi.10.1001/jama.2020.3204 https://www.ncbi.nlm.nih.gov/pubmed/32125362
  6. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical chacteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30211-7/fulltext
  7. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl Med 2020, Feb 28, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2002032
  8. Zhang J, Zhou L, Yang Y, et al. Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics. Lancet 2020;8: e11-e12. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30071-0/fulltext 9.
  9. Peng QY, Wang XT, Zhang LN, et al. Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic. Intensive Care Med 2020. https://doi.org/10.1007/s00134-020-05996-
Key clinical pearls in the medical management of hospitalized patients with coronavirus (Covid-19) infection