The American Heart Association is an organization of health care professionals dedicated to the prevention of heart disease and stroke. It should come as no surprise that the college’s annual meeting AHA 2020 had considerable attention on the emergency pandemic of our century.
As the SARS-CoV-2 pandemic continues to play out across the globe, the AHA 2020 annual meeting appropriately brought the emerging science from bench to bedside. While much is understood about the virus and its transmission, much remains in terms of understanding how the virus causes fatal disease in humans. There is an early and exponential viral replication phase which almost always occurs in the ambulatory setting. Unfortunately, the only approved antiviral therapy remdesivir is advised only for late stage patients presenting typically two weeks or longer with dyspnea the need for oxygen [1]. At this stage the two major pathologies are not viral replication but cytokine storm and endothelial injury and pathological micro-thrombosis [2, 3]. For these processes there are supportive data for the use of corticosteroids and antiplatelet/antithrombotic agents [4]. Because all of these treatments are only recommended for use in COVID-19 in severely symptomatic patients who are hospitalized and requiring oxygen, there remains a large treatment gap [5]. If therapies are only applied in the hospital according to guidelines, then there is no opportunity for community treatment with the aim of reducing hospitalization and death [5]. The treated mortality for COVID-19 requiring any form of oxygen is ~12% and for those who require mechanical ventilation, the death rate is ~23% [6]. Thus, the hospital and late treatment cannot be considered an adequate safety net.
The safe application of the NIH guidelines for COVID-19 appears to be in those under age 50 years with no comorbidities [7]. In this group, there is broad agreement that provided no serious symptoms develop, no treatment is warranted. However, for those over age 50 or at any age with comorbidities (heart, lung, kidney disease, diabetes, obesity, and cancer) ahead of the results of clinical trials, it is prudent to employ an ambulatory regimen to reduce the risk of hospitalization and death. The NIH guidelines call for shared decision-making between the physician and the patient in this common scenario where the NIH guidance cannot be safely applied. In most cases, the immediate use of at least two safe off-target antivirals (zinc sulfate, hydroxychloroquine, ivermectin, azithromycin, doxycycline) is advised. At day 5, or at the onset of pulmonary symptoms, corticosteroids should be used (inhaled budesonide, prednisone, hydrocortisone, dexamethasone). In those with heart or lung disease or patients with high thromboembolic risk, low-molecular weight heparin or a novel oral antithrombotic should be prescribed. This approach advances treatment that would have been started in the hospital into the home and on an emergency basis is believed to have a reasonable chance of reducing hospitalization or death [8]. Future AHA meetings are expected to update the audience on the rapid pace of clinical trial reports concerning early ambulatory therapy for COVID-19, which is the only treatment approach that has the possibility of reducing hospitalization and its complications, including death. Additionally, prolong untreated periods at home with unabated viral replication may be associated with cardiac injury and potentially long-term consequences of cardiac damage. Future research is needed, and physicians are cautioned at this time to respond to their patients with cardiovascular disease at the onset of illness and apply sequenced multidrug early ambulatory treatment.
In conclusion, the AHA has taken a leadership role in understanding and responding to the COVID-19 pandemic. It is becoming clear that contagion control has failed to quash the viral outbreak and that we must turn our attention to immediate early treatment to reduce the burgeoning tide of acutely ill patients in the community before hospitalization is needed. Prompt ambulatory treatment is an important pillar of global pandemic response that should have equal policy and press visibility along with contagion control, late-stage treatment, and mass vaccination.
References
1. Obireddy SR, Wing-Fu L. Tackling SARS-CoV-2 Infections using Remdesivir and Favipiravir as Therapeutic Options. Chembiochem. 2020 Oct 8. doi: 10.1002/cbic.202000595. Epub ahead of print. PMID: 33031623.
2. Zhang J, Tecson KM, McCullough PA. Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy. Rev Cardiovasc Med. 2020 Sep 30;21(3):315-319. doi: 10.31083/j.rcm.2020.03.126. PMID: 33070537.
3. Singhania N, Bansal S, Nimmatoori DP, Ejaz AA, McCullough PA, Singhania G. Current Overview on Hypercoagulability in COVID-19. Am J Cardiovasc Drugs. 2020 Oct;20(5):393-403. doi: 10.1007/s40256-020-00431-z. PMID: 32748336; PMCID: PMC7398761.
4. Jensen MP, George M, Gilroy D, Sofat R. Beyond Dexamethasone, Emerging Immuno-Thrombotic Therapies for COVID-19. Br J Clin Pharmacol. 2020 Sep 2. doi: 10.1111/bcp.14540. Epub ahead of print. PMID: 32881064.
5. Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2020 Apr 27:ciaa478. doi: 10.1093/cid/ciaa478. Epub ahead of print. PMID: 32338708; PMCID: PMC7197612.
6. Palazzuoli A, Ruberto F, De Ferrari GM, Forleo G, Secco GG, Ruocco GM, D'Ascenzo F, Mojoli F, Monticone S, Paggi A, Vicenzi M, Corcione S, Palazzo AG, Landolina M, Taravelli E, Tavazzi G, Blasi F, Mancone M, Birtolo LI, Alessandri F, Infusino F, Pugliese F, Fedele F, De Rosa FG, Emmett M, Schussler JM, McCullough PA, Tecson KM. Inpatient Mortality According to Level of Respiratory Support Received for Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019) Infection: A Prospective Multicenter Study. Crit Care Explor. 2020 Sep 18;2(9):e0220. doi: 10.1097/CCE.0000000000000220. PMID: 32984838; PMCID: PMC7505344.
7. https://www.covid19treatmentguidelines.nih.gov/
8. McCullough PA, Kelly RJ, Ruocco G, Lerma E, Tumlin J, Wheelan KR, Katz N, Lepor NE, Vijay K, Carter H, Singh B, McCullough SP, Bhambi BK, Palazzuoli A, De Ferrari GM, Milligan GP, Safder T, Tecson KM, Wang DD, McKinnon JE, O'Neill WW, Zervos M, Risch HA. Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. Am J Med. 2020 Aug 7:S0002-9343(20)30673-2. doi: 10.1016/j.amjmed.2020.07.003. Epub ahead of print. PMID: 32771461; PMCID: PMC7410805.
Illustration Collage: CoreDESIGN / pathdoc / shutterstock
