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Summary of COVID-19 Medications

The past year has seen tremendous changes due to the coronavirus 2019 (COVID-19) pandemic across multiple levels. While behavioral changes and social isolation helped with limiting the spread of the disease, certain medications were studied and have been shown to be of benefit in COVID-19 patients. In this article, we summarize some of these medications, the mechanism of action and add references to the major studies supporting them.

1-Glucocorticoids — Steroids are recommended for severely ill patients with COVID-19 who are on supplemental oxygen or ventilatory support [1,2].

2-Baricitinib is a selective JAK1 and JAK2 inhibitor used for the treatment of rheumatoid arthritis, and has been used in COVID-19 patients on the basis that it disrupts the activation of downstream signaling molecules and proinflammatory mediators[ 3].

3- Tocilizumab  — Markedly elevated inflammatory markers (including interleukin [IL]-6) are associated with critical and severe COVID-19, and blocking these it may prevent disease progression. Tocilizumab is a recombinant humanized monoclonal antibody that competitively inhibits the binding of interleukin-6 (IL-6) to its receptor (IL-6R) [4].

4Favipiravir is an RNA polymerase inhibitor available in some Asian countries for the treatment of influenza and mild COVID-19, and it is being evaluated in clinical trials for the treatment of COVID-19 in the United States and elsewhere [5].

5-Remdesivir — is an adenosine triphosphate analogue, which stops replication of the virus. It was first described in the literature in 2016 as a potential treatment for Ebola. The FDA granted full approval as a COVID-19 treatment on October 22, 2020, for hospitalized children ≥12 years and adults with COVID-19, regardless of disease severity [6]. 

6Hydroxychloroquine/chloroquine is not recommended in hospitalized patients given the lack of clear benefit and potential for toxicity. There is also for QTc prolongation and arrhythmias with the use of this medication [7].

7Monoclonal antibody therapy –In the United States, the following monoclonal antibody therapies are available for patients with mild to moderate infection in the outpatient setting [8,9]:

Bamlanivimab-etesevimab
Casirivimab-imdevimab
Sotrovimab

8Interferons – Interferon beta has been reported in the literature to inhibit COVID-19 replication in vitro. Defects in type 1 interferon production (which include interferon beta), have been associated with severe COVID-19 infections. However, clinical data so far do not support a clear benefit of interferon beta for severe COVID-19 [10].

9- IL-1 inhibitors – Interleukin-1 (IL-1) is a pro-inflammatory cytokine that has been associated with severe COVID-19, and several observational studies have suggested that IL-1 inhibitors, for example, Anakinra, is associated with reduced COVID-19-associated mortality [11].

10- Colchicine – Although there are some data demonstrating a benefit from Colchicine in mild to moderate COVID-19, the benefit is modest without a reduction in mortality, and adverse effects are common [12].

This is a brief summary of some of these medications. A registry of international clinical trials can be found at covid-trials.org.

A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and an assistant professor at the University of Jordan in Amman, Jordan.

References

[1] WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LCP, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JPT, Horby P, Jüni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Møller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Oct 6;324(13):1330-1341. doi: 10.1001/jama.2020.17023. PMID: 32876694; PMCID: PMC7489434.

[2] Rochwerg B, Siemieniuk RA, Agoritsas T, Lamontagne F, Askie L, Lytvyn L, Agarwal A, Leo YS, Macdonald H, Zeng L, Amin W, Burhan E, Bausch FJ, Calfee CS, Cecconi M, Chanda D, Du B, Geduld H, Gee P, Harley N, Hashimi M, Hunt B, Kabra SK, Kanda S, Kawano-Dourado L, Kim YJ, Kissoon N, Kwizera A, Mahaka I, Manai H, Mino G, Nsutebu E, Pshenichnaya N, Qadir N, Sabzwari S, Sarin R, Shankar-Hari M, Sharland M, Shen Y, Ranganathan SS, Souza JP, Stegemann M, De Sutter A, Ugarte S, Venkatapuram S, Dat VQ, Vuyiseka D, Wijewickrama A, Maguire B, Zeraatkar D, Bartoszko JJ, Ge L, Brignardello-Petersen R, Owen A, Guyatt G, Diaz J, Jacobs M, Vandvik PO. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379. Update in: BMJ. 2020 Nov 19;371:m4475. Update in: BMJ. 2021 Mar 31;372:n860. PMID: 32887691.

[3] Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, Marconi VC, Ruiz-Palacios GM, Hsieh L, Kline S, Tapson V, Iovine NM, Jain MK, Sweeney DA, El Sahly HM, Branche AR, Regalado Pineda J, Lye DC, Sandkovsky U, Luetkemeyer AF, Cohen SH, Finberg RW, Jackson PEH, Taiwo B, Paules CI, Arguinchona H, Erdmann N, Ahuja N, Frank M, Oh MD, Kim ES, Tan SY, Mularski RA, Nielsen H, Ponce PO, Taylor BS, Larson L, Rouphael NG, Saklawi Y, Cantos VD, Ko ER, Engemann JJ, Amin AN, Watanabe M, Billings J, Elie MC, Davey RT, Burgess TH, Ferreira J, Green M, Makowski M, Cardoso A, de Bono S, Bonnett T, Proschan M, Deye GA, Dempsey W, Nayak SU, Dodd LE, Beigel JH; ACTT-2 Study Group Members. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021 Mar 4;384(9):795-807. doi: 10.1056/NEJMoa2031994. Epub 2020 Dec 11. PMID: 33306283; PMCID: PMC7745180.

[4] Ghosn L, Chaimani A, Evrenoglou T, Davidson M, Graña C, Schmucker C, Bollig C, Henschke N, Sguassero Y, Nejstgaard CH, Menon S, Nguyen TV, Ferrand G, Kapp P, Riveros C, Ávila C, Devane D, Meerpohl JJ, Rada G, Hróbjartsson A, Grasselli G, Tovey D, Ravaud P, Boutron I. Interleukin-6 blocking agents for treating COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 Mar 18;3:CD013881. doi: 10.1002/14651858.CD013881. PMID: 33734435.

[5] Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, Kadam J, Wu W, Caracta CF, Tandon M. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021 Feb;103:62-71. doi: 10.1016/j.ijid.2020.11.142. Epub 2020 Nov 16. PMID: 33212256; PMCID: PMC7668212.

[6] Antinori S, Cossu MV, Ridolfo AL, Rech R, Bonazzetti C, Pagani G, Gubertini G, Coen M, Magni C, Castelli A, Borghi B, Colombo R, Giorgi R, Angeli E, Mileto D, Milazzo L, Vimercati S, Pellicciotta M, Corbellino M, Torre A, Rusconi S, Oreni L, Gismondo MR, Giacomelli A, Meroni L, Rizzardini G, Galli M. Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status. Pharmacol Res. 2020 Aug;158:104899. doi: 10.1016/j.phrs.2020.104899. Epub 2020 May 11. PMID: 32407959; PMCID: PMC7212963.

[7] Rochwerg B, Siemieniuk RA, Agoritsas T, Lamontagne F, Askie L, Lytvyn L, Agarwal A, Leo YS, Macdonald H, Zeng L, Amin W, Burhan E, Bausch FJ, Calfee CS, Cecconi M, Chanda D, Du B, Geduld H, Gee P, Harley N, Hashimi M, Hunt B, Kabra SK, Kanda S, Kawano-Dourado L, Kim YJ, Kissoon N, Kwizera A, Mahaka I, Manai H, Mino G, Nsutebu E, Pshenichnaya N, Qadir N, Sabzwari S, Sarin R, Shankar-Hari M, Sharland M, Shen Y, Ranganathan SS, Souza JP, Stegemann M, De Sutter A, Ugarte S, Venkatapuram S, Dat VQ, Vuyiseka D, Wijewickrama A, Maguire B, Zeraatkar D, Bartoszko JJ, Ge L, Brignardello-Petersen R, Owen A, Guyatt G, Diaz J, Jacobs M, Vandvik PO. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379. Update in: BMJ. 2020 Nov 19;371:m4475. Update in: BMJ. 2021 Mar 31;372:n860. PMID: 32887691.

[8] Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Adams AC, Van Naarden J, Custer KL, Shen L, Durante M, Oakley G, Schade AE, Sabo J, Patel DR, Klekotka P, Skovronsky DM; BLAZE-1 Investigators. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):229-237. doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28. PMID: 33113295; PMCID: PMC7646625.

[9] Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17. PMID: 33332778; PMCID: PMC7781102.

[10] WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernández García C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, García PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portolés A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Røttingen JA, Swaminathan S. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med. 2021 Feb 11;384(6):497-511. doi: 10.1056/NEJMoa2023184. Epub 2020 Dec 2. PMID: 33264556; PMCID: PMC7727327.

[11] Huet T, Beaussier H, Voisin O, Jouveshomme S, Dauriat G, Lazareth I, Sacco E, Naccache JM, Bézie Y, Laplanche S, Le Berre A, Le Pavec J, Salmeron S, Emmerich J, Mourad JJ, Chatellier G, Hayem G. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2020 Jul;2(7):e393-e400. doi: 10.1016/S2665-9913(20)30164-8. Epub 2020 May 29. PMID: 32835245; PMCID: PMC7259909.

[12] Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, Metallidis S, Sianos G, Baltagiannis S, Panagopoulos P, Dolianitis K, Randou E, Syrigos K, Kotanidou A, Koulouris NG, Milionis H, Sipsas N, Gogos C, Tsoukalas G, Olympios CD, Tsagalou E, Migdalis I, Gerakari S, Angelidis C, Alexopoulos D, Davlouros P, Hahalis G, Kanonidis I, Katritsis D, Kolettis T, Manolis AS, Michalis L, Naka KK, Pyrgakis VN, Toutouzas KP, Triposkiadis F, Tsioufis K, Vavouranakis E, Martinèz-Dolz L, Reimers B, Stefanini GG, Cleman M, Goudevenos J, Tsiodras S, Tousoulis D, Iliodromitis E, Mehran R, Dangas G, Stefanadis C; GRECCO-19 investigators. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. PMID: 32579195; PMCID: PMC7315286.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Trends in COVID-19 in-hospital mortality: Insights from the AHA COVID-19 CVD registry

Information on the survival trends of hospitalized COVID-19 patients is important for physicians to identify trends and track the efficacy of hospital-based care in real-world practice. The American Heart Association’s (AHA) COVID-19 Cardiovascular Disease (CVD) Registry was put in place in April 2020 with the objective of improving nation-wide surveillance of hospitalized patients with COVID-19.1 Early data derived from this registry were presented at scientific sessions #AHA20 last year. This blog summarizes a more recent analysis by Gregory A. Roth and colleagues, looking at trends in patient characteristics and COVID-19 in-hospital mortality in the United States during the pandemic.2

This retrospective study published in JAMA Network Open included 20 736 hospitalized patients from the AHA COVID-19 CVD registry at 107 hospitals in 31 states. Undertaken as part of the Global Burden of Disease Study, the objective was to quantify changes in in-hospital mortality rates during the first 9 months of the pandemic, and understand if any observed changes were associated with differences over time in the characteristics of presenting patients. The data were analyzed to show comparative trends across 4 periods in 2020: March and April; May and June; July and August; and September through November.

There was a gradual decline in the numbers of admitted patients in the registry, with 11 901 patients admitted in March or April, down to 2010 patients in September through November. In terms of the patient demographics, 45.9% were women, the proportion of which slightly increased over time. The mean age was 61.2 ±17.9 years which decreased from March -April through September-November. 58.4% of patients were hypertensive. 35% were diabetic, and 18.3% had pulmonary disease. The mean BMI was in the obese range (30.8 ± 8.5) and increased a small amount through November.

Almost a quarter of patients were receiving supplemental oxygen on admission. This proportion increased from 23% in March – April to 35.9% in September through November. This was despite the presence of interstitial infiltrates on admission decreasing from 70.7% of patients to 60.8% during the corresponding periods. In contrast to supplemental oxygen, however, the use of mechanical ventilation decreased substantially from 23.3% to 13.9% during the same periods. The use of glucocorticoids and remdesivir increased substantially, potentially reflecting the emergence of randomized evidence of its efficacy during that time and the US Food and Drug Administration (FDA) announcement of remdesivir emergency use authorization on May 1, 2020.3 The mean duration of hospital stay also showed a reduction from 10.7±12.1 days to 7.5 ± 6.8 days.

A total of 3271 in-hospital deaths recorded from March through November 2020, corresponding to overall in-hospital mortality of 15.8%. In-hospital mortality rates declined as time progressed, with 19.1% in March-April, 11.9% in May-June, 11% in July-August, and 10.8% in September- November. Adjusted odds for in-hospital death were also significantly lower for all 3 later time periods studied, compared with March-April. Increasing age was the factor most strongly associated with death, with the figure depicting the adjusted odds ratios across different age groups [Figure 1]. Male sex, BMI > 45, and presences of comorbidities, specifically cancer, cerebrovascular disease, diabetes, and heart failure were independently associated with in-hospital death.

The greatest reduction in the in-hospital mortality rates occurred between March and May 2020, with high mortality rates falling by a massive 38% from March and April 2020 by May and June, followed by a modest further decrease by November. Notably, this difference in mortality rates persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity. In the face of only minor changes in the characteristics of admitted patients described above, the authors have thus put forward some hypotheses that might explain these trends of decreasing mortality rates over time.

One of them is the extremely high hospital census and rapid implementation of new measures (i.e. isolation and personal protection procedures) especially in locations with very high rates of COVID-19 in March and April. This is consistent with the observation of the most rapid declines in mortality rates between the months of March – April and May – June, when health care workers gradually became more familiar with new procedures.

Changes in treatment protocols may also have contributed to this decreased mortality. The observed increased use of supplemental oxygen and decreased use of mechanical ventilation in the registry data could be explained by trends in respiratory care that emerged as the pandemic progressed, particularly the efficacious modalities of noninvasive ventilation, high flow nasal oxygen, and prone positioning, although these modalities were not captured in the registry. Substantially increased use of steroids and remdesivir may also have contributed to better outcomes.

Few limitations exist: the analysis was retrospective, with varying sample sizes due to the voluntary nature of enrolment in the registry. Certain treatment modalities were not captured. There was potential for bias due to confounding from unobserved or unrecorded characteristics in the estimation of associations, and as such causality cannot be inferred. Furthermore, it is important to note that this analysis included data from before the rollout of vaccines, and it would be interesting to see these more contemporary trends from the AHA COVID-19 CVD registry in future analyses.

Needless to say, such registry-based analyses provide important data on trends in mortality and contemporary management practices in the face of rapidly evolving hospital dynamics during the pandemic. While randomized controlled trials are essential to investigate potential treatments and inform evidence-based practice, the utility of such registries in identifying mortality and treatment trends in real-world practice, and indeed using this information to implement best practices, cannot be understated.

References

  1. Alger HM, Rutan C, Williams JH IV, et al. American Heart Association COVID-19 CVD Registry powered by Get With The Guidelines. Circ Cardiovasc Qual Outcomes. 2020;13(8):e006967.
  2. Roth GA, Emmons-Bell S, Alger HM, et al. Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic. JAMA Netw Open. 2021;4(5):e218828.
  3. US Food and Drug Administration. Emergency Use Authorization (EUA) for emergency use of Veklury® (remdesivir) for the treatment of hospitalized patients with severe 2019 coronavirus disease (COVID-19). Published October 22, 2020. Accessed June 4, 2021. https://www.fda.gov/media/137564/download

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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COVID-19 and BMI – What Have We Learned? More insights from the United Kingdom

The COVID-19 pandemic has skyrocketed many fields of healthcare – basic science research, outcome-based research, and epidemiological factors affecting healthcare. We already know obesity affects >4 in 10 adults in the United States and contributes to diabetes, heart disease, ultimately leading to increased morbidity and mortality1.  Based on prior experience, we have learned that obesity is associated with an increased risk of other respiratory viruses, such as influenza. These same patients tended to have a higher risk of hospitalization and death, along with longer lengths of stay and mechanical ventilation compared to patients who have normal weight2.

In January of 2021, researchers used the American Heart Association’s COVID-19 Cardiovascular Disease Registry to look at the effect of obesity across different groups’ mortality, need for mechanical ventilation or both. Analysis of data from 88 hospitals in the US showed that classes I to III obesity were associated with a higher risk of in-hospital death or mechanical ventilation compared to normal weight when these patients are hospitalized with COVID-19. The association was strongest in adults <50 and weakest in adults >70 years of age. This was the first study to show the harmful effects of obesity on COVID-19 outcomes may be limited to people under 50 rather than those that are older and obese. There could be a number of reasons for this observation – including comorbid conditions such as diabetes, hypertension, or even delays in seeking care3. As a critical care provider, this study definitely made me evaluate risk factors for younger patients (and even family members) differently.

In a time where one study is not simply the end-all-be-all, a more recent study from the United Kingdom had a similar message. The study was led by Nuffield Department of Primary Care Health Sciences and had 6.9 million patients – which is an outstanding number! And what did they discover??

Figure A shows patients with low BMI (<18.5) had an increase in COVID-19 related admissions to the ICU along with a steady increase in admissions to the ICU as the BMI increased. Figure B shows a linear association across the whole BMI range for death due to COVID-194.  Dr. Carmen Piernas, lead author of the study said: “Our Study shows that even very modest excess weight is associated with greater risks of severe COVID-19 complications and the risks rise sharply as BMI increases. Also, risks associated with excess weight are greatest in people <50 years, while weight has little to no effect on your chances of developing severe COVID-19 after age 80. These findings suggest that vaccination policies should prioritize people with obesity.” The impact of obesity was most marked in people in the youngest age range of 20-39. The study shows that obesity is not only a chronic disease but also a risk factor for acute illness or death. Taking it one step further, health care providers across the spectrum will have to work harder to help provide evidence-based treatments for patients to help reduce their weight.

One of the most striking aspects of this study was the number of patients they tracked in the outpatient setting who ended up needing to go to the hospital. They tracked these patients in their disease course in hopes of giving us information for people in the general community rather than those already admitted to the hospital. At this time, there is no study looking to see if weight reduction specifically reduces the risk of severe COVID-19 outcomes, but I would be interested in such a study.

There was also a significant interaction between BMI and self-reported ethnicity for hospital admissions and death due to COVID-19, with Black people having a higher risk than white people. It’s unclear as to why this association exists in a country where all the citizens have free access to healthcare. There are a few hypotheses but nothing concrete has been established.

Overall, with the addition of this large study plus what we have known before, we can be confident that obesity continues to have significant health implications. I hope we never see another pandemic but if we do, I’m confident what we have learned over the past year will help us treat our patients more efficiently and effectively.

References

  1. Romero-Coral A, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancent. 2006;368:666-678.
  2. Jain S, Chaves SS. Obesity and influenza. Clinic Infect Disease. 2011;53:422-424.
  3. Hendren N, et al. Association of body mass index and age with morbidity and mortality in patients hospitalized with COVID-19 results from the American Heart Association COVID-19 cardiovascular disease registry. Circ. 2021;143:135-144
  4. Gao M, et al. Associations between body-mass index and COVID-19 severity in 6.9 million people in England: a prospective, community-based, cohort study. Lancet. 2021;

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Can Vitamin C Prevent COVID-19?

The outbreak of COVID-19 has created a global public health crisis. Our knowledge continues to be limited about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, and halt the progression and severity of symptoms and complications related to COVID-19 are desperately needed. In the midst of the COVID-19 pandemic, health promotion measures, such as proper nutrition, physical activity, rest, and stress reduction measures have been advocated.  More recently, attention has been shifted to vitamin supplementation as a means to keep American’s health and immune system in optimal status.

Source: https://www.heart.org/en/healthy-living/healthy-eating/add-color

Adequate intake of micronutrients is critical for optimal health, growth and development, and healthy aging. However,  the Dietary Guidelines for Americans 2015–2020 highlight low-consumption of important nutrients including vitamins A, C, D and E, calcium, magnesium, iron, potassium, choline and fiber, with variations by age groups.1   Vitamin C has recently gained attention as a potential micronutrient in the prevention of COVID-19.  Vitamin C has been known for promoting the oxidant scavenging activity of the skin, potentially protecting against environmental oxidative stress, enhancing chemotaxis, phagocytosis, and microbial killing.2

Based on previous evidence, oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, hospital length of stay, and time on mechanical ventilation for severe respiratory infections3-4

Given the favorable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, trials are currently underway to determine its effect in hospitalized patients with COVID-19.4-5  Although there are currently no published results of these clinical trials due to the novelty of SARS-CoV-2 infection, there is pathophysiologic rationale for exploring the use of vitamins such as Vitamin C in this global pandemic.6

Source: https://www.heart.org/en/news/2019/07/01/low-vitamin-d-in-babies-predicts-blood-pressure-problems-for-older-kids

While we await for results from these trials, we need to continue being vigilant, and adhere to a varied and balanced diet with an abundance of fruits and vegetables and the essential nutrients known to contribute to the normal immune system functioning.  Vitamin C supplementation could present a safe and inexpensive approach to prevention of respiratory diseases, and perhaps aid in COVID-19.7

Avoidance of deficiencies and identification of suboptimal intakes of these micronutrients in targeted groups of patients and in distinct and highly sensitive populations could help to strengthen the resilience of people to the COVID-19 pandemic. It will be also important to highlight evidence-based public health messages, to prevent false and misleading claims about the benefits of vitamin supplements. It will also be important to communicate the exploratory state of research on micronutrients and COVID-19 infection and that no diet will prevent or cure COVID-19 infection. Frequent handwashing and social distancing will continue to be critical to reduce transmission during this pandemic.8

 

References:

  1. Blumberg JB, Frei B, Fulgoni VL, Weaver CM, Zeisel SH. Contribution of Dietary Supplements to Nutritional Adequacy in Various Adult Age Groups. Nutrients. 2017;9(12):1325. Published 2017 Dec 6. doi:10.3390/nu9121325
  2. U.S. Department of Health and Human Services. U.S. Department of Agriculture [(accessed on 15 March 2017)];2015–2020 Dietary Guidelines for Americans. (8th ed.). 2015 Available online: http://health.gov/dietaryguidelines/2015/guidelines/
  3. Holford P, Carr AC, Jovic TH, et al. Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Nutrients. 2020;12(12):3760. Published 2020 Dec 7. doi:10.3390/nu12123760
  4. Carr AC. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Crit Care. 2020;24(1):133. Published 2020 Apr 7. doi:10.1186/s13054-020-02851-4
  5. Zhang J, Rao X, Li Y, et al. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intensive Care. 2021;11(1):5. Published 2021 Jan 9. doi:10.1186/s13613-020-00792-3
  6. Jovic TH, Ali SR, Ibrahim N, et al. Could Vitamins Help in the Fight Against COVID-19?. Nutrients. 2020;12(9):2550. Published 2020 Aug 23. doi:10.3390/nu12092550
  7. Allegra A, Tonacci A, Pioggia G, Musolino C, Gangemi S. Vitamin deficiency as risk factor for SARS-CoV-2 infection: correlation with susceptibility and prognosis. Eur Rev Med Pharmacol Sci. 2020;24(18):9721-9738. doi:10.26355/eurrev_202009_23064
  8. Richardson DP, Lovegrove JA. Nutritional status of micronutrients as a possible and modifiable risk factor for COVID-19: a UK perspective [published online ahead of print, 2020 Aug 20]. Br J Nutr. 2020;1-7. doi:10.1017/S000711452000330X

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

 

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A Roadmap for Understanding COVID Vaccines

Yes, we are still in the middle of the COVID pandemic. With the help of more people getting vaccinated and mask mandates in effect, a post-pandemic world is no longer a mere imagination. While waiting for the pandemic to be over, there are some doubts about whether the COVID vaccines should be cleared to facilitate a faster transition back to normal life.

  1.  What are the leading COVID vaccines?

    Figure: Overview of the diverse types of vaccines, and their potential advantages and disadvantages (Dong et al. 2020).

Currently, two COVID-19 vaccines are authorized and then recommended for use in the United States–the Pfizer-BioNTech COVID-19 vaccine(Polack et al. 2020) and the Moderna’s COVID-19 vaccine(Baden et al. 2020). Both of the vaccines used a cutting-edge technology, the messenger RNA (mRNA) vaccine which has been developed in the 1990s.

As of December 28th, 2020, three other COVID-19 vaccines are undergoing large-scale (Phase 3) clinical trials in the United States: AstraZeneca’s COVID-19 vaccine(Knoll and Wonodi 2021), Janssen’s COVID-19 vaccine and Novavax’s COVID-19 vaccine(Sadoff et al. 2021). Both the AstraZeneca COVID-19 vaccine and Janssen’s COVID-19 vaccines (Johnson& Johnson) used a weakened adenovirus vector strategy to tackle the spike protein on the SARS-CoV-2 virus. The weakened virus vector serves as a “Trojan horse” to deliver “information” to the cells in order to stimulate the memory of immune defense against SARS-CoV-2 virus. The adenovirus-based vaccines are relatively less foreign to the public, currently they are used against a wide variety of pathogens such as Mycobacterium tuberculosis, human immunodeficiency virus (HIV), and Plasmodium falciparum. The AstraZeneca COVID-19 vaccine has already authorized to use in Europe on January 12th, 2021 and possibly obtains approval in the United States early 2021. On January 29th, Johnson& Johnson announced its interim clinical Phase 3 trial results and a single-shot Janssen COVID-19 vaccine is on the way for FDA approval.

Novavax COVID-19 vaccine, a protein subunit-based vaccine, just announced its interim UK Phase 3 clinical trial results on January 28th, 2021. It shows promising protection to the SARS-CoV-2 virus, as well as the UK and South Africa variants. The company has already signed purchase agreements with many governments including Australia and Canada.

Two other vaccines– Russia’s sputnik V vaccine and China’s COVID-19 vaccine developed by Sinovac Biotech are also the lead runners in the vaccine race. The sputnik V vaccine which has obtained authorization to use in Russia back in November 2020, just published its Phase 3 data on February 2nd(Logunov et al. 2021). It’s an adenovirus-based vaccine, similar as the AstraZeneca COVID-19 vaccine and Janssen’s COVID-19 vaccine.

China’s COVID vaccine used a relatively well-understood technology: an inactivated SARS-CoV-2 virus. The inactivated virus vaccine approach has been implemented for a wide range of vaccines such as polio vaccine, hepatitis A vaccine, rabies vaccine and most flu vaccines. So far it received some inconsistent results from Brazil, Indonesia and Turkey and it’s not applicable in the United States. Overall, the efficacy is encouraging (50.38% to 91.25%) and requires more data to reach a more consistent result.

  1. How to understand the efficacy?

It’s a numbers game or is it? The high efficacy (95%) data released from Pfizer and Moderna at the end of last year received with great applause. The 70% protection starting after a first dose from AstraZeneca seems less impressive. The AstraZeneca COVID-19 vaccine confirms 100% protection against severe disease, hospitalization and death in the primary analysis of Phase 3 trial suggesting a total success. The recent Phase 3 trial results from Johnson& Johnson’s single-shot vaccine shows 72% effective in the United States and 66% effective overall at preventing moderate to severe COVID-19, 28 days after vaccination. The efficacy number simply cannot be interpreted as the higher the better. Like all of the clinical trials, compounding factors need to take into consideration. Their vaccine impact may depend on sex, age, genetics, geography, the timing of assessment of the end-point, the percentage of population affected by new variant compared to the original variant.

The thing matters the most is to reduce hospitalization and death. So far most of the leading vaccines have showed great promise. At the current stage, whatever vaccine is available to you could protect you from getting serious disease and prevent the virus spread to your loved ones one way or another. Herd immunity could finally be reached if enough people are getting vaccinated in the near future.

  1. mRNA technology: what is it? And is it safe?

Considering mRNA vaccine is the new kid on the block, it’s understandable that certain hesitancy and reluctance towards getting vaccinated. mRNA therapy has been developed and used to target certain types of cancer for more than twenty years. It has recently been used to target SARS-CoV-2 virus. The nucleic acid fragment of SARS-CoV-2 virus spike protein is packaged in a lipid nanoparticle. Like how most vaccine works, it tricks your body to formulate a defense memory using a small piece of information from the virus. When the actual attacks occurred, you are protected with a pre-programmed defense mechanism already. It does not change your DNA. It just helps your body to remember what it feels like to successfully combat the virus. Some of the side effects from clinical trials could be another reason to cause hesitancy. Don’t blame the messenger. The individual response elicited by the vaccines is just a small fraction of what you might experience when the real attack occurs. Some extreme allergic responses, a few reported in a million cases are rare. The chance is as similar as winning a Powerball or Mega Millions lottery. At the end of the day, the benefits still outweigh the risks.

  1. Early progress and new variants

Israel’s vaccination program shows encouraging outcome, results from a recently published preprint(Chodick et al. 2021). It’s in agreement with the Phase 3 clinical trial results from Pfizer. Data collected by Israel’s Ministry of Health shows a 41% reduction in confirmed COVID-19 infections in people aged 60 and order. Close to 90% of that age group has been administered with the first dose of Pfizer’s 2-dose vaccine. For people aged 59 and younger, the infected cases and hospitalization are also dropped.

Viruses like SARS-CoV-2 mutate all the time. There are 3 concerned variants: the UK variant (B.1.1.7), Brazil (P.1) and South Africa (B.1.351) have already been found in the United States. With the surge of new variants of SARS-CoV-2, the effectiveness of the COVID-19 vaccine also dropped. Some new data from Johnson& Johnson and Novavax suggest that the COVID-19 vaccines can prevent a lot of mild and moderate cases, and are still very effective against preventing hospitalization and deaths. Other company such as Moderna, has already developed booster shots to combat new variants. If most of the population got vaccinated, it will stop the virus’s replication and ultimately stop mutation completely. The recommended measure is to vaccine as many people as possible at current stage.

In conclusion, no matter which vaccine you got or are going to get, as long as it’s approved and authorized by the FDA, the chance of having effective protection is still very good. At the end of the day, the benefits outweigh the risks.

Reference

Baden, Lindsey R., Hana M. El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, et al. 2020. “Efficacy and Safety of the MRNA-1273 SARS-CoV-2 Vaccine.” New England Journal of Medicine. https://doi.org/10.1056/nejmoa2035389.

Chodick, Gabriel, Lilac Tene, Tal Patalon, Sivan Gazit, Amir Ben Tov, Dani Cohen, and Khitam Muhsen. 2021. “The Effectiveness of the First Dose of BNT162b2 Vaccine in Reducing SARS-CoV-2 Infection 13-24 Days after Immunization: Real-World Evidence.” MedRxiv, January, 2021.01.27.21250612. https://doi.org/10.1101/2021.01.27.21250612.

Dong, Yetian, Tong Dai, Yujun Wei, Long Zhang, Min Zheng, and Fangfang Zhou. 2020. “A Systematic Review of SARS-CoV-2 Vaccine Candidates.” Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-020-00352-y.

Knoll, Maria Deloria, and Chizoba Wonodi. 2021. “Oxford–AstraZeneca COVID-19 Vaccine Efficacy.” The Lancet. https://doi.org/10.1016/S0140-6736(20)32623-4.

Logunov, Denis Y, Inna V Dolzhikova, Dmitry V Shcheblyakov, Amir I Tukhvatulin, Olga V Zubkova, Alina S Dzharullaeva, Anna V Kovyrshina, et al. 2021. “Safety and Efficacy of an RAd26 and RAd5 Vector-Based Heterologous Prime-Boost COVID-19 Vaccine: An Interim Analysis of a Randomised Controlled Phase 3 Trial in Russia.” The Lancet, February. https://doi.org/10.1016/S0140-6736(21)00234-8.

Polack, Fernando P., Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, John L. Perez, et al. 2020. “Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine.” New England Journal of Medicine. https://doi.org/10.1056/nejmoa2034577.

Sadoff, Jerald, Mathieu Le Gars, Georgi Shukarev, Dirk Heerwegh, Carla Truyers, Anne M. de Groot, Jeroen Stoop, et al. 2021. “Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine.” New England Journal of Medicine. https://doi.org/10.1056/nejmoa2034201.

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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To Vaccinate or Not Against COVID-19 During Pregnancy: A Pregnant Cardiology Fellow’s Humble Perspective

When news of the approval of the Pfizer vaccine surfaced, I felt a sense of anxiety. There was no data on pregnant women in the COVID-19 vaccine trials. As a medical professional, we have been trained to apply for evidenced-based medicine and baseline patient characteristics of trial participants to the patients we plan to treat. But what if your pregnancy status was not studied in the trial during a global pandemic? How might you weigh the unknown risks of the vaccine to your growing fetus with the risk of COVID-19 infection while pregnant?

Making the Decision

A few days passed when I received an email from Occupational Health that my cardiology fellowship program would be part of the Phase I distribution of the vaccine. The following day, my midwife conveyed to me that the OB department would align with the American College of Obstetrics and Gynecology (ACOG) Practice Advisory Statement:

“ACOG recommends that COVID-19 vaccines should not be withheld from pregnant individuals who meet criteria for vaccination based on ACIP-recommended priority groups.”

I felt a sense of relief that I would not be prohibited from getting the vaccine if I chose to do so yet also felt a sense of panic when I read the following:

“Vaccines currently available under Emergency Use Authorization (EUA) have not been tested in pregnant women. Therefore, there are no safety data specific to use in pregnancy.”

As a trained medical professional and protective mother, the overwhelming number of daily decisions we make to ensure the safety of our babies are overwhelming- no sushi, no wine, no retinoids or other harmful active ingredients found in our beloved skin care regimens, no hot tubs… I could go on.

However, the challenge of navigating the emotions of fear and uncertainty about the vaccine became incomparable to the following facts:

mRNA Does Not Alter Your DNA

These vaccines are not live virus vaccines and do not use an adjuvant to augment the efficacy of the vaccine. It does not enter the nucleus or alter human DNA.

Risk of Exposure

My job involves routinely interacting with patients and performing aerosolizing procedures, which places me at increased risk for exposure to COVID-19.

Symptomatic Pregnant Patients Infected With COVID-19 Are at Increased Risk of Severe Illness

This includes hospitalization in the intensive care unit (ICU), the need for intubation and mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and death.

I decided that getting vaccinated was safer than getting COVID-19. I also consulted with my partner who is also my husband and the father to our developing fetus. Although ultimately it was my decision to make, I felt comforted knowing he was 100% on board with me proceeding with vaccination based on the above as well.

Getting Vaccinated and the Side Effects

I received both doses of the Pfizer vaccine, the first dose at 20 weeks and the second dose at 23 weeks gestation. With the first dose of the vaccine, I only experienced arm soreness that peaked on day two. With the second dose, I experienced a mild headache and mild bilateral upper extremity soreness but with two doses of acetaminophen, I continued to work at full capacity and performed intraoperative transesophageal echocardiograms without issues.

I am now 25 weeks pregnant and feel a sense of pride that I made this decision to protect myself and my unborn child. I have received many texts and messages inquiring about how I made my choice. Questions such as “would your decision change if you were in your first trimester before organogenesis was complete?” or “would you get vaccinated while trying to conceive?” were a few memorable ones. I firmly believe it is your right as a woman to make this difficult decision when there is no safety data available.  Personally, yes, I would have still made the decision to vaccinate.

Lastly, I will join many of the other scientists and advocates out there who demand that pregnant and lactating women be included in future vaccine research trials http://vax.pregnancyethics.org/prevent-guidance. Track records of vaccine safety should exist for expectant mothers to help guide and improve vaccination rates.  Here is to hoping for a better year that allows each and every one of us access to the COVID-19 vaccine no matter what country, gender, pregnancy status, lact

ation, status, or employment status we bear.

Stay safe and stay healthy,

Kyla Lara-Breitinger, MD, MS

References:

https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/12/vaccinating-pregnant-and-lactating-patients-against-covid-19

https://s3.amazonaws.com/cdn.smfm.org/media/2632/FDA_final.pdf

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

 

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Coronavirus Disease 2019 Vaccine

Coronavirus disease 2019 (Covid-19) has been declared a pandemic by the world health organization (WHO) on March 11, 2020. Since the outbreak, the WHO reported more than 70 million confirmed cases, and 1.5 million deaths globally. In the US, nearly 300,000 lost their lives and currently, we are facing another surge of cases with a record-breaking 3,124 new deaths in a single day last week. Over the past year, scientists, physicians, and pharmaceutical companies did phenomenal efforts to develop a safe and effective vaccine.

Finally, on December 11 2020, The Food and Drug Administration has issued an emergency use authorization (EUA) for Pfizer and BioNTech’s coronavirus vaccine (based on a 17 to 4 vote with one abstention). It is important to note that an EUA is not equivalent to FDA approval. As the latter requires safety data for at least six months. The FDA clearance occurred in a record-breaking time frame for a complicated process that usually takes years. This EUA makes the United States the sixth country to clear the vaccine after Bahrain, Canada, Saudi Arabia, Mexico, and the United Kingdom. In this blog, I will review the data behind the EUA.

The study behind the FDA’s EUA was a multinational, phase 2/3, Placebo-controlled, observer-blinded randomized trial. Between July 2020, and November 2020, 43,548 participants (16 years and older) who were healthy or had stable medical conditions underwent 1:1 randomization to receive vaccine or placebo (saline). Of which, 36,523 received two doses (21 days apart) and completed the 2 months follow up. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among the vaccine group and 162 cases among the placebo group. Hence the vaccine was 95% effective in preventing Covid-19. Moreover, among the 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in the placebo group and 1 in the vaccine group.

Figure 1: Efficacy of the vaccine against Covid-19 after the First Dose.

Each symbol represents Covid-19 cases starting on a given day; filled symbols represent severe Covid-19 cases. The inset shows the same data on an enlarged y-axis, through 21 days.

The noted side effects were short-term mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and similar in both groups (0.6% in the vaccine group and 0.5% in the placebo group).

Figure 2: Safety outcomes of the vaccine.

The Vaccine works simply as it contains a small piece of the virus’s mRNA that instructs cells in the body to produce the virus’s distinctive “spike” protein. After receiving the vaccine, the body will manufacture a piece of the COVID-19 virus named spike protein, which does not cause disease but triggers the immune system to learn to react defensively. Given the novel mechanism, theoretically, it carries no risk of infection, as it only codes for a piece of the virus. It is also important to note that currently, it is unclear how long the vaccine will provide protection, nor is there evidence that the vaccine prevents transmission of SARS-CoV-2 from person to person.

Given the promising results and the EUA, Pfizer is planning on shipping 2.9 million doses over this week and 100 million doses of the vaccine by next March. The pharmaceutical giant has a deal with the U.S. government, under that agreement, the vaccines will be free to the public. Understandably, the distribution will be in phases with the most critical workers and vulnerable people being on top of the list. At this point, strict monitoring of any side effects will be enforced at all sites. Apart from the approved vaccine, Moderna’s vaccine utilized a similar technology and is currently under review by the FDA and could obtain an EUA soon. Other pharmaceutical companies such as Johnson & Johnson, Oxford, and AstraZeneca, are in late-stage trials and their vaccines could be authorized in the near future. This Vaccine is the light at the end of the tunnel which gives humanity hope to reach an endpoint to this pandemic. In the meantime, we must practice social distancing, trust the data, and get vaccinated!

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Reflections of 2020: adaptations and lessons learned

2020 came, a pandemic hit, and 2020 left. It was an extraordinary year in which words such as unprecedented, exponential and social distancing forced their way into our ordinary vocabulary. Hopefully, we won’t have to live another year like that in our lifetimes, but let’s exercise some cautious optimism in that respect. It took a toll on everyone, both physically and mentally, but perhaps the brunt of it was borne by essential workers, notably those involved in healthcare. Many had to work extra hours, often at the expense of time spent with loved ones, often young children. Many of us have not been able to visit family in almost a year, due to travel restrictions or for fear of transmitting the virus to elderly parents and relatives. Many have suffered setbacks in training and professional development. We are all tired – COVID fatigue is real. We all had it bad, in some way or the other, but in the face of adversity lies the opportunity: the pandemic forced us to adapt, and it looks like the lessons we learned last year are certainly applicable for the immediately foreseeable future.

COVID 19 served to magnify existing global healthcare disparities, triggering important conversations around it, and with that, hope for rectification. It saw the more widespread adoption of telemedicine as an integral component of healthcare delivery.  It made the scientific community realize the importance of good quality research and clinical trials and the benefits of sharing knowledge and collaboration.

In pathology class at medical school, we are taught cellular responses to stress and toxic insults. Adaptations are one of them:  Robbins pathology defines them as reversible functional and structural responses to more severe physiologic stresses and some pathologic stimuli, during which new but altered steady states are achieved, allowing the cell to survive and continue to function.1

COVID-19 forced adaptations at a far greater magnitude, and we are now at the altered steady state of what we call a “new normal”. Just as much as the pandemic forced healthcare systems to adapt to the crisis, it presented an opportunity for introspection and re-evaluation of our lives on a personal level, and there are important lessons I’ve learned in the process.

Communication: Just as with telemedicine, 2020 also saw us embrace social media in a way we hadn’t before. Indeed, in an increasingly digital global landscape, many of us had to depend on virtual interactions as being the primary and often the sole form of interaction. In addition to public social media handles, many physicians took to their private accounts to combat misinformation, providing an important channel for public health messaging among friends and social circles outside of medicine. With the advent of vaccines, this appears to be even more important in breaking down important information and allaying fears related to its side effects.

Adaptations in learning: Also virtually, we learnt to modify methods of learning, with conferences and meetings adapting to virtual platforms and regular educational content being far more widely available. Paradoxically, this has perhaps resulted in increased exposure and visibility of especially early career physicians, with opportunities for global networking and collaborations. Not too different from the times of in-person conferences, we now look forward to “meeting” friends on webinar platforms, with the camaraderie and friendly exchanges with colleagues in healthcare probably being more therapeutic than the educational content itself.

Building a support network: Perhaps my greatest learning from the last year is the importance of friendship, support, and mentorship. While we’ve been trained to adapt and be strong, this is a pandemic none of us have been equipped for. We’re used to being care-givers, not receivers, but in remembering that we’re also human and vulnerable, it is only healthy to actively seek out and lean on one’s support network: this can be family, friends, sometimes colleagues: to talk, chat, cry it out, or rant.

Mentorship: We have all faced challenges that were unprecedented and it was more than just training that was affected. Navigating through the uncertainties of early career practice can be challenging even in the most ordinary of times; hence the perspectives, solid life advice, and clarity provided by good mentorship during pandemic times cannot be understated. Additionally, the stress of working in a pandemic can give rise to inopportune moments, and I couldn’t be more grateful for mentors that have cut me slack, forgiven the shortcomings, and taught me resilience. It’s a lesson in maturity that I hope I can pay forward in my dealings with junior physicians as well.

Gratitude: Count your blessings and force yourself to do this.  Pause to celebrate the small victories.

As far as the science of adaptations goes, Robbins pathology will also tell you that when the stress is eliminated, the cell can recover to its original state without having suffered any harmful consequences.1 While it looks like we’re in for a few more challenging months before the “stressful” triggers might show any signs of waning, my optimistic takeaway is precisely the hope of this recovery to its original state, or at the very least, some semblance of a better new normal.

2020 is the year that taught me resilience, and it is a testament to our ability to adapt and pivot. I’m sure we’ve all found different mechanisms of adaptations that work for each of us, and I’d love to hear yours!

References

  1. Kumar v, Abbas AK, Aster JC. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death. In Robbins & Cotran Pathologic Basis of Disease. 10th ed. New York, NY: Elsevier; 2020.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Hopes for 2021

As 2020 concluded with all of the unprecedented events, with the tragedies people had to suffer and are still suffering from, with all the good and bad, we enter the New Year of 2021 with some hope; hoping for better health, better strategies to combat what we are dealing with in this pandemic, and being more responsible for each other.

COVID-19 Pandemic

COVID-19 pandemic has changed how we live our lives, and the impact of this pandemic will likely last at least a few years, if not more after the pandemic is over. There are a lot of “unknowns” about COVID-19 infection, including the long-term effects of this infection and the effectiveness of some medications, that we will get to encounter and manage in the next several years.

COVID-19 Vaccine

With multiple effective vaccines discovered recently, healthcare workers were given priority to get the vaccine, followed by more vulnerable patients, including the elderly and those with significant comorbidities. The Centers of Disease Control and Prevention (CDC) website provides helpful information on the currently available vaccines in the United States (US), Pfizer, and Moderna, including their storage, preparation, and expected side effects (Link is provided below) [1].  The hope is that by the Spring of 2021, 75% of the population in the United States will be vaccinated.  Moreover, efforts by international organizations, including the World Health Organization (WHO), to distribute the vaccine to all countries are ongoing [2].

COVID-19 New Strains

We have seen the discovery of new strains of COVID-19 infection in the United Kingdom and, most recently, the US. These new mutant strains of COVID-19 may not be covered by the available vaccines, as such, the vaccine is an additional layer of protection, with the other protection measures, including social distancing, masks, and hygiene, which may be the most important way to prevent the spread of these new strains at this point of time.

With all that being said, our hopes for a “normal 2021” depend on how we handle the COVID-19 pandemic, we may not see everything going back to normal in 2021, but we can work on making the initial right steps now so that we have less grief, less “loss,” fewer travel restrictions, with healthier and happier upcoming years!!

Special thank you to my sister, Rawan Ya’acoub, an assistant professor of Doctor of Pharmacy/Clinical Pharmacology at the University of Jordan in Amman, Jordan, who helped me write this blog, and for all of her support.

 

References

  • S. COVID-19 Vaccine Product Information: https://www.cdc.gov/vaccines/covid-19/info-by-product/index.html
  • COVID-19 vaccines: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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COVID Fatigue

Anesthesia alert! This overhead call alerting pending intubation can be heard bellowing throughout the hallways of my medical center several times throughout the day and is seemingly the soundtrack of COVID-19. My typical routine is to pause, make sure it’s not sounding the alarm to my patient’s room, and then continue with my workday.

It has been 304 days since the WHO has declared COVID-19 a pandemic. COVID numbers at my medical center continue to rise, and although the vaccine is widely available to hospital staff, we are continuing to see some of our highest numbers since the beginning of the pandemic.

As a general cardiology fellow on the advanced heart failure service at a high volume mechanical circulatory support and transplant center, we really get to know our patients while taking care of them during their index hospitalizations. For the past two weeks, I’ve gotten to know one patient in particular. She presented in cardiogenic shock, was stabilized on inotropes and a balloon pump, with plans for upcoming destination therapy LVAD implantation.

Every day when we come to her bedside, she is on FaceTime with her partner. Today, the day before her LVAD implantation, we walked to her bedside, and once again she was on FaceTime with her devoted partner. She is obviously loved. Considering that she was going for LVAD the following day, we spent a bit more time explaining the procedure in-depth to the patient and her partner. After discussing all of the technical details, she timidly asked “Do you think my partner could come to spend the night with me tonight? I just need to see my love and it’s been so long.” You could see the tears begin to drop from her face and her partners.

Donning and doffing, wearing the N95, not knowing what anyone looks like without their mask; things have become routine. Health-care workers have adapted so well to the ever-demanding challenges of practicing medicine in the era of COVID-19. We’ve made guidelines, adjusted our practice, established routines, and found ways to provide quality medical care in the darkest of times. We’ve become oddly accustomed to these necessary rituals in order to protect ourselves, our loved ones, and the patients that we care for.

But none of this is normal.

At that moment, when we told our patient that the person who loved her the most in this world could not sit with her the night before a life-altering surgery, it became dramatically apparent to me that all of this is abnormal. The weight of 304 days of pandemic sat heavy in my heart and the sounds of endless anesthesia alerts echoed in my head.

Depression and burnout were prevalent in the healthcare field even before the pandemic. COVID-19 has undoubtedly placed an added burden on all healthcare providers. I implore people to take time off if you can, spend time with family if able, and be thoughtful of your mental well being because this past year has been anything but normal.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”