The Protective Role of Anti-Hypertension Medication Among Patients with Comorbidities for COVID-19 Outcomes

Millions of people around the world take Angiotensin-converting enzyme inhibitors (ACEi) and Angiotensin II receptor blockers (ARB) to manage hypertension, heart failure, and coronary artery disease. Concerns of ACEi and ARB potentially increasing the risk of COVID-19 illness severity and mortality among vulnerable populations heightened once scientists reported that risk factors for developing complications included being older, male, and having cardiovascular comorbidities1. One comprehensive study using over 17,000 primary care records found that chronic heart disease has a hazard ratio of 1.57 for COVID-19 related death and the hazard ratio remained high at 1.17 even when accounting for confounding variables, suggesting that people with heart disease are at increased risk of mortality2. In the same study, high blood pressure or hypertension diagnoses were associated with hazard ratio of 0.89, a lower risk of COVID-19 mortality compared to people with normal blood pressure, but insight into how age, sex, comorbidities, and medications influence outcomes were not directly addressed. Such findings fueled a debate about whether ACEI/ARB should be maintained or withdrawn in patients with COVID-19.

The role of ACEi and ARBS drugs in COVID-19 outcomes among cardiovascular patients also became a point of interest due to their mechanism of action in the human body. ACEi and ARB act on the renin-angiotensin-aldosterone system (RAAS), a hormone system important for regulating blood pressure, fluid balance, and inflammation processes that affect cardiovascular health outcomes. While ACEi and ARB drugs are used as the first line of treatment to manage vasoconstriction, there is a question as to how these medications can alter the RAAS balance. In a previous blog, we discussed how the SARS-CoV-2 virus uses the  of angiotensin-converting enzyme 2 (ACE2) receptor to enter host target cells3. This receptor not only acts as the entry point for the virus, but normally acts as a crucial element for regulating RAAS biochemical processes. The inflammatory, tissue damaging, and vasoconstriction effects of Angiotensin II (Ang II) in the body are mitigated by ACE2 activity, and ARB and ACEi drugs also target the Ang II protein4. COVID-19 related research has provided a new understanding of how underlying disease states, behavioral habits like smoking, or genetics could influence ACE2 activity in the body. The unique collaboration between clinicians and scientists during the COVID-19 pandemic has provided new mechanistic insight about how the complex RAAS pathway and the factors that influence disease progression.

Ongoing population studies such as The International Study of Inflammation in COVID-19 (ISIC) and The Michigan Medicine COVID-19 Cohort (M2C2) make use of detailed medical records bio-banked human samples, and advanced statistical modeling to evaluate the potential benefits and harms of ACEi and ARB medications. Using stored blood samples and electronic medical records from patients hospitalized specifically for COVID-19, researchers were able to assess for an association between ACEi or ARB use and in-hospital patient outcomes, such as requiring mechanical ventilation or admission into intensive care. The research team overseeing the ISIC and M2C2 studies analyzed the health outcomes of about 1,600 people hospitalized for COVID-19 and reported that patients taking ACEi or ARB had about 10% mortality compared to 14% who were not on those medications5. Among those taking medications, 24% of patients required ventilation during hospitalization, compared to 20% of those not any treatment. These results were surprising as people taking medication also had significantly more comorbidities such as diabetes compared with the non-ACEi/ARB group. Knowing that people who use ACE inhibitors or ARB are not more susceptible to severe COVID-19 illness or increased risk of mortality during hospitalization has now led to the widely accepted practice of not discontinuing these drugs in people who are infected with SARS-CoV-2. In fact, people on anti-hypertensive medication had lower levels of inflammation biomarkers during hospital admission compared to those who don’t take ACEi and ARB drugs. This insight suggests that ACEi/ARB drugs could counter the inflammatory effects of COVID-19, which could be an interesting future direction of this research. Large scale studies have been valuable for providing evidence on how to mitigate detrimental outcomes during the COVID-19 pandemic and future findings will continue to influence guidelines for monitoring cardiovascular homeostasis, targeting treatments for vulnerable populations, and managing chronic illnesses.


  1. Patel AB, & Verma A. (2020). COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. https://doi.org/10.1001/jama.2020.4812
  2. Williamson EJ, Walker AJ, Bhaskaran K, et al. (2020). Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430-436. doi:1038/s41586-020-2521-4
  3. Raizada MK, & Ferreira AJ, (2007). ACE2: A New Target for Cardiovascular Disease Therapeutics. Journal of Cardiovascular Pharmacology, 50(2), 112–119. https://doi.org/10.1097/FJC.0b013e3180986219
  4. Monterrosa Mena, J. ACE-2 and Immune System Changes in Smokers May Underlie COVID-19 Vulnerability. https://earlycareervoice.professional.heart.org/ace-2-and-immune-system-changes-in-smokers-may-underlie-covid-19-vulnerability/
  5. Pan N, Hayek S, the ISIC Group, et al. (2021). Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID‐ Journal of the American Heart Association, 10(24), e023535. https://doi.org/10.1161/JAHA.121.023535

“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 health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”


Insights About COVID-19 Health Outcomes in Smokers from Hospital Records

Early in the COVID-19 pandemic, clinicians noticed that some patients with pre-existing medical conditions were at higher risk of severe illness and death. Since then, many observational studies confirmed that people with diabetes, asthma, or cardiovascular disease had a substantially higher risk of COVID-19-related complications and death1,2. Such studies typically use hospital patient records to study relationships between individual risk factors, like age and sex, and long-term health outcomes. However, studies using hospital record data revealed that smokers may be underrepresented among patients with COVID-19, as highlighted by a recent review study of publications reporting smoking prevalence and clinical outcomes in patients diagnosed with COVID-193. The review highlights that only a single study out of 15 research articles examined had reported a prevalence of smokers among patients with COVID-19 that resembles the smoking prevalence of the general population. Such findings, raises the question of whether a smoker’s paradox exists with the COVID-19 pandemic. The smoker’s paradox refers to the observational phenomenon of smokers exhibiting improved prognosis and decreased short-term mortality, following cardiovascular events. This idea has been mostly debunked now as a bias in the analysis of observational data and smoking is not considered to be a causative factor that improves health outcomes4. So, what considerations should be taken when interpreting health records of patients in order understand whether smokers fare worse COVID-19 outcomes than non-smokers?

Questioning Data Quality and Biases in Patient Record Data

Smoking is associated with many immediate and long-term health consequences, and initiates disease promoting mechanism in cardiopulmonary tissues. A low representation of smokers in hospitalized COVID-19 patients may be due to biases in patient record data collection. A small percentage of people who perceive stigma associated with smoker status may actually conceal smoker status during a primary care visit5. Furthermore, smoker screening often does not include questions about smokeless tobacco, electronic cigarette use, and second-hand smoke use, despite the rise in popularity in electronic nicotine delivery systems and cigarette alternatives6. Standardization and improved tobacco-related electronic health record questionnaires may begin to address the question of how much tobacco smoke a person is exposed to by including questions that cover sources of exposure, quantity of use, and duration of exposure. Collecting patient data that covers a larger range of exposure possibilities including having someone else in the home that smokers, or individual behaviors of switching from traditional cigarettes to electronic cigarettes, smoking cessation patterns, and years of use may provide better insight into how smoking behaviors influence health outcomes. In the context of the COVID-19 pandemic, smokers’ status is difficult to ascertain in patients who are intubated, sedated, and unresponsive. Closely tracking individual smoker status over time is helpful in those situations when a patient’s care plan should include tobacco withdrawal symptom management.

Smoking directly influences cardiovascular and respiratory health outcomes and using hospital data to derive associations with COVID-19 health outcomes is prone to confounding bias, reverse causation, and inappropriate adjustments in analysis models. In the future, it be possible to use human biomarkers to uncover the specific health effects from smoking. This might include correlating urinary levels of nicotine and cotinine to understand the burden of different tobacco products. For now, research using animal models to assess the health effects of traditional smoking and electronic cigarettes provide insight into the short- and long-term consequences of smoking and elucidates the biochemical processes that exacerbate disease including tissue repair processes, inflammation, and oxidative stress. Understanding the mechanistic processes involved in the exacerbation of COVID-19 disease among smokers may ultimately help identify biomarkers of disease progression and pharmacological treatments for vulnerable populations.


  1. Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430-436. doi:1038/s41586-020-2521-4
  2. Why lighting up and COVID-19 don’t mix. American Heart Association News. https://www.heart.org/en/news/2020/05/05/why-lighting-up-and-covid-19-dont-mix#:~:text=Studies%20from%20Wuhan%2C%20China%2C%20where,%2C%20compared%20to%20non%2Dsmokers.
  3. Usman MS, Siddiqi TJ, Khan MS, et al. Is there a smoker’s paradox in COVID-19? BMJ EBM. 2021;26(6):279-284. doi:1136/bmjebm-2020-111492
  4. Doi SA, Islam N, Sulaiman K, et al. Demystifying Smoker’s Paradox: A Propensity Score–Weighted Analysis in Patients Hospitalized With Acute Heart Failure. JAHA. 2019;8(23). https://www.ahajournals.org/doi/10.1161/JAHA.119.013056
  5. Stuber J, Galea S. Who conceals their smoking status from their health care provider? Nicotine & Tobacco Research. 2009;11(3):303-307. doi:1093/ntr/ntn024
  6. LeLaurin JH, Theis RP, Thompson LA, et al. Tobacco-Related Counseling and Documentation in Adolescent Primary Care Practice: Challenges and Opportunities. Nicotine & Tobacco Research. 2020;22(6):1023-1029. doi:1093/ntr/ntz076

“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 health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”


Ramadan, COVID-19 and the cardiac patient

With the dawn of the Islamic lunar month of Ramadan, many Muslims around the world begin observing an absolute fast from dawn to dusk, abstaining from food, drink, and oral medications. The fast naturally also entails a change in lifestyle, sleeping patterns, and adjustments of salt and fluid intake, all of which have implications for the cardiac patient. Furthermore, as they are generally known to be on multiple medications, depending on the number of hours of fasting, there might be a need for adjusting drugs, doses, and timings.

Cardiac patients span across a wide range of diseases and differ in terms of symptoms, acuity, and hemodynamic stability. As such, while it might be entirely appropriate for stable patients to observe the fast, with adjustments to lifestyle, others who are less so may need to be advised against fasting, particularly as the sick are exempted. There is a paucity of data on best practices for fasting among cardiac patients. This blog provides a brief summary of the available data, some general suggestions, and links to useful resources pertinent to patients with common cardiac conditions on fasting during Ramadan.

Stable Coronary artery disease: Few observational studies suggest that with good monitoring, fasting may be safe in patients with stable treated coronary artery disease (CAD), particularly with normal left ventricular ejection fraction (EF), provided they adhere to medications.1-3

In fact, among stable patients with a previous history of cardiovascular disease (CVD), fasting during Ramadan has been shown to significantly improve 10-year Framingham cardiac risk score, as well as cardiovascular risk factors such as lipid profile, body mass index (BMI), and systolic blood pressure.4

Acute myocardial infarction (MI): Unlike stable CAD, however, in patients with a recent acute MI or immediate post-cardiac surgery, abstinence from fasting following the 6-week period of either of these events has been advised.5,6

Heart failure (HF): A prospective observational study examining the effect of Ramadan fasting on patients with chronic HF and reduced ejection fraction (< 40%), noted that as many as 92% of the patients that fasted had no changes or improved symptoms, while symptoms worsened in a minority of patients (8%).7 Furthermore, those with worsening symptoms were significantly less likely to have adhered to fluid and salt restrictions, and heart failure medications (p<0.0001). This clearly underscores the need for ensuring compliance with appropriately timed medications, particularly diuretics, in order to prevent acute decompensation of HF.

The British Islamic Medical Association has a structured guideline of recommendations based on risk for fasting among patients with heart failure:6

  • HF with preserved ejection fraction (HFpEF), and HF with reduced EF (up to an LV EF 35%) are at low/moderate risk for fasting (i.e. decision not to fast at the discretion of medical opinion and patient’s ability).6
  • Severe, but not advanced, heart failure is at high risk for fasting and should be advised not to fast. This would include patients on Cardiac Resynchronization Therapy (CRT) .6
  • Patients with advanced heart failure (including those on Left Ventricular Assist Devices), decompensated HF requiring large doses of diuretics 5, and those with severe pulmonary hypertension, are deemed very high risk, and MUST be advised against fasting.6

Hypertension: Fasting during Ramadan is generally well-tolerated in patients with well-controlled essential hypertension on the continuation of previous drug treatment 5,8, supported by ambulatory BP measurement (ABPM) data in observational studies.9-10. However, patients with resistant hypertension should be advised not to fast until their blood pressure is reasonably controlled.5 The key to blood pressure maintenance during Ramadan lies in compliance with medications, and non-pharmacological measures such as a low-salt diet.11. In those with fluctuating BP, home blood pressure monitoring with medication adjustment may be a feasible option.

Adjustment of medications: Cardiac medications are vital, and non-compliance has the potential to be life-threatening. Patients should be advised on adherence to medication, and efforts be made to ensure compliance, by adjusting dose and timings, or switching to a class of medication that might be a more compliant alternative.8 For drugs with two daily doses, it’s advisable to take them with as wide a gap as possible during non-fasting hours.8 In case a medication requires more than twice daily dosing, an adjustment that allows for better compliance may be preferred.

Antihypertensive drugs: For twice-daily medication, dose timings may need to be changed to coincide with the early morning meal (Suhoor) and the breaking-of-fast meal (Iftar).8 A switch to a once-daily medication with long-acting preparations may be preferred.8,11

Diuretics: Diuretics are particularly unpopular among patients who either stop or reduce its doses during Ramadan. Diuretics may also worsen fasting-associated dehydration (especially in hot weather), with non-compliance resulting in uncontrolled hypertension and decompensation of heart failure. If the indication is hypertension, switching to a suitable alternative is reasonable.6 However, strict compliance with diuretics must be advised among those with HF especially those with reduced EF. They may also be prescribed during the non-fasting period of the day (i.e. early evening), where there is minimal risk of associated dehydration.5 Alternatively, patients may consider taking it at dawn (suhoor) to prevent frequent micturition and disturbed night sleep.6

Anticoagulants: Compliance must be ensured for those requiring therapeutic anticoagulation, irrespective of indication, with patients being advised of the risks of stroke or systemic embolism in case of non-adherence.12,13 Some older small-scale observational studies have reported that Ramadan fasting does not appear to adversely influence the efficacy or safety of warfarin.14, 15 However, more recent data suggest that Ramadan fasting does in fact influence the therapeutic effect of warfarin in terms of lowered time spent in therapeutic range (TTR) with a reduced proportion of patients achieving therapeutic PT-INR and consequent increased risk of poor anticoagulation control.16, 17 As such, closer monitoring or dosage adjustments are necessary for patients maintained at the higher end of INR target ranges.16 This should extend to the post-Ramadan period, particularly in the elderly as they are more prone to over-anticoagulation and consequently the risk of bleeding.17, 18 ).

There is no randomized evidence on dosing adjustments for Novel oral anticoagulants (NOACs) with fasting during Ramadan.12 However, clinical practice suggests that drugs are taken once or twice daily, such as NOACs, do not require an adjustment.12 . Among patients on twice-daily NOACs such as apixaban, a switch to once-daily rivaroxaban might be feasible.6 Those taking rivaroxaban should be asked to take the NOAC with food even during the month of Ramadan.12

Antiplatelet medications: Patients must be strictly advised to continue dual antiplatelet therapy (DAPT), especially in case of a recent MI or percutaneous coronary stent implantation, with clear information on the adverse outcomes of non-compliance such as acute stent thrombosis, MI, and even death.6 In terms of P2Y12 inhibitors, given pharmacokinetics of ticagrelor, if twice-daily dosing proves challenging, a switch to single-dose P2Y12 inhibitors such as clopidogrel or prasugrel (if appropriate), may be considered.6

Ramadan, COVID-19, and vaccine uptake: With the rollout of vaccines currently underway globally, there are concerns about vaccine hesitancy, based on whether the intramuscular injection invalidates the fast, any possible side-effects, and if indeed the fast may have to be broken.19  Scholars have clarified that vaccination does NOT invalidate the fast and such clarifications must be widely disseminated among both cardiac patients and the general public in order to maximize vaccine uptake.20

The bottom line to good heart health during Ramadan remains in good communication and preemptive discussions. Although the current climate of the COVID-19 pandemic poses challenges to in-patient visits and physical examinations, virtual consultations must be leveraged to optimize cardiac care during the month of fasting. Some useful resources have been linked in the references. This blog is by no means exhaustive, and decisions regarding individual patients’ suitability for fasting and medication adjustments must be made following individualized discussions with their respective physicians, particularly as the duration of the fast varies in different geographical locations and as such, not all data derived from studies can be extrapolated generically.


  1. Salim I, Al Suwaidi J, Ghadban W, et al. Impact of religious Ramadan fasting on cardiovascular disease: a systematic review of the literature. Curr Med Res Opin. 2013;29(4):343-54.
  2. Al Suwaidi J, Zubaid M, Al-Mahmeed WA, et al. Impact of fasting in Ramadan in patients with cardiac disease. Saudi Med J. 2005;26(10):1579-83
  3. Mousavi M, Mirkarimi S, Rahmani, Get al. Ramadan fast in patients with coronary artery disease. Iran Red Crescent Med J. 2014;16:e7887.
  4. Nematy M, Alinezhad-Namaghi M, Rashed MM, et al. Effects of Ramadan fasting on cardiovascular risk factors: a prospective observational study. Nutr J. 2012;11:69.
  5. Chamsi-Pasha H, Ahmed WH, Al-Shaibi KF. The cardiac patient during Ramadan and Hajj. J Saudi Heart Assoc. 2014;26(4):212-5.
  6. Ramadan Rapid Review & Recommendations – British Islamic Medical Association. Available at: https://britishima.org/wp-content/uploads/2020/05/Ramadan-Rapid-Review-Recommendations-v1.2.pdf (Accessed on 10th April 2021)
  7. Abazid RM, Khalaf HH, Sakr HI, et al. Effects of Ramadan fasting on the symptoms of chronic heart failure. Saudi Med J. 2018;39(4):395-400.
  8. Aadil N, Houti IE, Moussamih S. Drug intake during Ramadan. BMJ. 2004;329(7469):778-82.
  9. Perk G, Ghanem J, Aamar S, Ben-Ishay D, Bursztyn M. The effect of the fast of Ramadan on ambulatory blood pressure in treated hypertensives. J Hum Hypertens. 2001;15(10):723-5.
  10. Habbal R, Azzouzi L, Adnan K, et al. Variations tensionnelles au cours du mois de Ramadan [Variations of blood pressure during the month of Ramadan]. Arch Mal Coeur Vaiss. 1998;91(8):995-8.
  11. Chamsi-Pasha M, Chamsi-Pasha H. The cardiac patient in Ramadan. Avicenna J Med. 2016 ;6(2):33-8.
  12. Hersi AS, Alhebaishi YS, Hamoui O, et al. Practical perspectives on the use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation: A view from the Middle East and North Africa. J Saudi Heart Assoc. 2018;30(2):122-139.
  13. Batarfi A, Alenezi H, Alshehri A, et al. Patient-guided modifications of oral anticoagulant drug intake during Ramadan fasting: a multicenter cross-sectional study. J Thromb Thrombolysis. 2021;51(2):485-493.
  14. Saour JN, Sieck J, Khan M, et al. Does Ramadan fasting complicate anticoagulation therapy?. Ann Saudi Med 1989; 9: 538– 40.
  15. Chamsi‐Pasha H, Ahmed WH. The effect of fasting in Ramadan on patients with heart disease. Saudi Med J 2004; 25: 47– 51.
  16. Lai Y, Cheen M, Lim S, et al. The effects of fasting in Muslim patients taking warfarin. J Thromb Haemost 2014; 12: 349– 54
  17. Sridharan K, Al Banna R, Qader AM, et al. Does fasting during Ramadan influence the therapeutic effect of warfarin? J Clin Pharm Ther. 2021 Feb;46(1):86-92.
  18. Awiwi MO, Yagli ZA, Elbir F, et al. The effects of Ramadan fasting on patients with prosthetic heart valve taking warfarin for anticoagulation. J Saudi Heart Assoc. 2017;29(1):1-6.
  19. Ali SN, Hanif W, Patel K, Khunti K; South Asian Health Foundation, UK. Ramadan and COVID-19 vaccine hesitancy-a call for action. Lancet. 2021:S0140-6736(21)00779-0.
  20. Sharifain H. COVID-19 vaccine does not invalid the fast during Ramadan: Abdul Rehman Al Sudais. Available at: https://www.haramainsharifain.com/2021/03/covid-19-vaccine-does-not-invalid-fast.html. (Accessed on: April 12 2021)

On the Basis of Sex: Are males more vulnerable in severity and mortality from COVID-19?

Fig1: Data source: The sex, Gender and Covid-19 Project. (https://globalhealth5050.org/the-sex-gender-and-covid-19-project/about-us/)

As we just passed our first anniversary of fighting COVID-19, we are in a better position than we used to be a year ago. Nationwide vaccine efforts encourage us to see the light at the end of the tunnel. However, the virus is still lurking around and always finds its way back in many unpredictable forms as it evolves rapidly. We need to stay vigilant and use what we learned from the previous years’ knowledge to guide us defend any future attacks. One pertinent piece of information we discovered is that COVID-19 attacks us unequally. People are over 65 years old and people with any underlying complications are more at risk. Another important discovery is that there is a sex difference in infection, severity, and death among women and men.

In most countries, the incidence of infection (percent of cases) is similar in both sexes. However, men consistently develop more serious symptoms and have more mortalities across age groups on a global level (Fig1). More specifically, men account for about 59% to 75% of total mortality1. It’s indisputable that sex is an important factor when it comes to understand and combat COVID-19. Here are a couple of candidate mechanisms potentially contributing to sex-biased COVID-19 mortality.


Many sex differences in the manifestation of disease development have long been attributed to sex hormones, particularly in the realm of immune responses. Both innate and adaptive immune responses are affected by sex-dependent factors2. Males are more susceptible to infections caused by parasites, fungi, bacteria, and viruses, one of the possible determining factors is sex hormone3. More specifically, the immune-suppressive androgens reside in males and immune protective estrogens reside in females. Females might produce more antibodies and launch a stronger immune defense to infection because of estrogens, while males lack the advantage to react the same way. Female hormones, estrogens, can ameliorate the severity of influenza infections by suppressing pro-inflammatory responses in mice4. The anti-inflammatory activity of estrogen is potentially through the regulation of the SOCS3 and STAT3 signaling pathways, specifically to promote the progression of the anti-inflammatory process towards the IL-10-dependent pathway in macrophages5. Sex hormones can regulate the immune response via regulating circadian rhythm, microbial composition, and transcriptional regulation such as estrogen receptors (ERs) and peroxisome proliferator-activated receptors (PPARs)6.

Fig2: Potential mechanisms of male bias of COVID-19 mortality7.

Sex chromosomes

One of the fundamental differences between men and women is the X and Y sex chromosomes. Females have two X chromosomes with a functional one and an inactive one to maintain the balance of chromosomal X gene dosage, while males only have one functional X chromosome and one Y chromosome to maintain the identity of sex-specific effects and testis development. This evolutional advantage in females provides a “back-up” plan in case of a “disease gene” on X chromosome inherited from either the maternal or paternal side. Some genes can escape from X chromosomal inactivation and consequently express higher levels. The gene encoding a receptor that is responsible for SAS-CoV-2 virus cellular entry is called ACE2. ACE2 locates at X chromosome and is potentially a target for ineffective chromosome inactivation, and which could cause a female-biased increased level of ACE2 expression7. A higher level of ACE2 in females promotes viral clearance. On the contrary, a lower level of ACE2 causes dysregulated inflammation, increased cardiovascular comorbidities, increased risk of respiratory failure in males7 (Fig2). Other inflammatory response-related genes on the X chromosome include pattern recognition receptors such as toll-like receptor 7 (TLR7), TLR8, interleukin-1 receptor-associated genes, and NFKB essential modulator genes8. Additionally, it has been shown that TLR3, TLR7, and TLR9 are female-biased while TLR2 and TLR4 are male-biased. These differences potentially reveal why males and females respond to infection differently7,8. The research on understanding sex dimorphisms in immunity is critical to help us fight COVID-19 more effectively.

In conclusion, strong evidence shows that COVID-19 affects men and women unequally. Aside from socio-economic, lifestyle and environmental differences, biology plays an important role in male-biased COVID-19 severity and mortality. To understand and combat infection more precisely, we need to consider sex as a biological variable and develop therapeutic strategies for men and women respectively.


  1. Griffith DM, Sharma G, Holliday CS, Enyia OK, Valliere M, Semlow AR, Stewart EC, Blumenthal RS. Men and COVID-19: A Biopsychosocial Approach to Understanding Sex Differences in Mortality and Recommendations for Practice and Policy Interventions. Preventing chronic disease. 2020;17:E63.
  2. Markle JG, Fish EN. SeXX matters in immunity. Trends in Immunology. 2014;35(3):97–104.
  3. Klein SL. The effects of hormones on sex differences in infection: from genes to behavior. Neuroscience & Biobehavioral Reviews. 2000;24(6):627–638.
  4. Robinson DP, Lorenzo ME, Jian W, Klein SL. Elevated 17β-Estradiol Protects Females from Influenza A Virus Pathogenesis by Suppressing Inflammatory Responses. PLOS Pathogens. 2011;7(7):e1002149.
  5. Villa A, Rizzi N, Vegeto E, Ciana P, Maggi A. Estrogen accelerates the resolution of inflammation in macrophagic cells. Scientific Reports. 2015;5(1):15224.
  6. Taneja V. Sex Hormones Determine Immune Response. Frontiers in immunology. 2018;9:1931.
  7. Bienvenu LA, Noonan J, Wang X, Peter K. Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities. Cardiovascular Research. 2020;116(14):2197–2206.
  8. Pradhan A, Olsson P-E. Sex differences in severity and mortality from COVID-19: are males more vulnerable? Biology of Sex Differences. 2020;11(1):53.

“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.”


CDC Guidelines for the Vaccinated Population

It has been more than a year since the World Health Organization declared COVID-19 as a pandemic. In the past year, more than 130 million people were diagnosed with COVID-19, and we have lost 3 million lives globally. Within a record time, several effective vaccines were developed. Given that the vaccinated population is rapidly increasing, the Centers for disease control and prevention (CDC) released new guidelines for the fully vaccinated population. (figure 1)

CDC recommendations for the fully vaccinated population:

  • You can gather indoors with fully vaccinated people without social distancing or wearing a mask.
  • You can gather indoors with unvaccinated people from 1 household without social distancing or wearing a mask. Unless they are considered to be at high risk for severe COVID infection.
  • For domestic travel, you do not need to get tested before or after travel or self-quarantine after travel.
  • You do NOT need to get tested before leaving the United States unless your destination requires it.
  • You still need to show a negative test result or documentation of recovery from COVID-19 before boarding a flight to the United States.
  • You should still get tested 3-5 days after international travel.
  • You do NOT need to self-quarantine after arriving in the United States.
  • If you’ve been around someone who has COVID-19, you do not need to stay away from others or get tested unless you have symptoms.

Based on solid data, we know that all three approved vaccines in the United States are very effective in preventing the disease, especially deaths and severe forms. However, there are a few questions that remain to be determined in the next few months.

  • What is the effectiveness of different vaccines on the various new COVID-19 variants?
  • Can fully vaccinate people spread the disease?
  • For how long is the vaccine effective?

Currently, in the United States, the average number of shots per day is 3 million. Earlier this week, the public health agency reported more than 4 million shots were administered in 1 day. According to the CDC, more than 60 million people are fully vaccinated and 104.2 million U.S. residents, or 31% of the population, have received at least one vaccine dose. With the current pace, vaccines will be available for every adult in the United States by the end of May. Since the beginning of this pandemic, we have faced a lot of challenges in different aspects but finally now as the number of cases is significantly decreasing and the vaccinated population is expanding, we are definitely heading in the right direction!

Figure 1:
CDC recommendations for fully vaccinated people


  • https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated-guidance.html

“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.”


Effects of COVID-19 on Acute Ischaemic Stroke care: Comparative insights from Get With The Guidelines-Stroke registry

Much like acute myocardial infarctions, the optimal management of acute ischaemic stroke (AIS) is extremely time-sensitive. The foundation of favorable outcomes of AIS lies in the timely presentation and acute intervention by means of either intravenous thrombolysis and mechanical thrombectomy. Especially earlier on during the COVID-19 pandemic, there was a concern regarding a decline in non-COVID acute medical admissions, as well as hospital-based challenges to appropriate and timely delivery of acute stroke care.

A study led by Dr Pratyaksh Srivastava and colleagues, published in Stroke, uses data from the American Heart Association (AHA)’s Get With The Guidelines Stroke (GWTG-Stroke)® registry, to compare characteristics, treatment patterns, and in-hospital outcomes of 81,084 patients over two time periods: before COVID and after the first reported case of COVID-19 (1). The AHA’s GWTG-Stroke registry is a validated and reliable national registry of adults with stroke in the United States (2,3). This blog provides a brief summary of the key findings of this analysis.

The study cohort and comparisons:

81,084 AIS patients were included over a period extending from 01st November 2019 to 29th June 2020, from among 458 participating hospitals with at least one positive COVID-19 patient. They were divided into two groups, according to the first reported case of COVID-19 in the registry. The pre-COVID group consisting of 39,113 patients (01st November 2019 to 3rd February 2020) and the during COVID group, consisting of 41,971 patients (4th February 2020 to 29th June 2020).

The two groups were compared for characteristics, treatment patterns, and outcomes. These analyses were repeated in sensitivity analyses, comparing a later during COVID-19 time period (1st April 2020 to 29th June 2020) to the same pre-COVID-19 time period. There were no differences in general characteristics among patients of the two time periods. 48.8% of the cohort were women. 61.9% were White. 2.7% of patients in the during COVID-19 group had a diagnosis of COVID-19.

Key findings from the study & implications:

There was a 15.3% average reduction of stroke presentations per week in the during-COVID-time period (3rd February 2020 to 24th May 2020) when compared with similar months in 2019. This is perhaps a reflection of general trends (4,5) in the immediate aftermath of the pandemic, partially reflecting an anticipated lack of capacity in overburdened health systems, the effect of shelters in place and social distancing disorders (5), and patients delaying or avoiding seeking medical care due to concerns of contracting COVID-19(6).

Treatment patterns:

Similar rates of acute interventions for AIS were observed in pre-COVID and during-COVID time periods. There were no differences in rates of intravenous alteplase (11.7% vs. 11.4%, p=0.26) or endovascular therapy (10.2% vs. 10.1%, p=0.90) pre- and during COVID respectively.

Furthermore, there were also no additional delays in administering care. Median door to needle times (46 [32-65] minutes vs 46 [33-64] minutes; p= 0.69) and door to endovascular times (86 [53-129] minutes vs 90 [54-134] minutes; p=0.06) were not different between the pre-COVID and during COVID periods respectively. This is crucial and encouraging data, given the time-sensitive nature of acute stroke care and the delays that were anticipated during the COVID-19 period, from having to don personal protective equipment (PPE).

Also, door to computed tomography (CT) time was slightly shorter during the COVID-19 time period (median 35 [14-100] vs 37 [15-111] mins, p<0.001). A significant uptake of telestroke consult was observed during the COVID-19 period as compared with pre-COVID (6.0% vs 7.1%; p <0.0001).

GWTG-Stroke quality measures: 

Slight decreases were observed in rates of timely IV alteplase administration, prescription of antithrombotics at discharge, dysphagia screen, smoking cessation counseling, stroke education, and rehabilitation consideration in the during-COVID-19 group.  Despite this, these quality measures remained above the 85% target, suggesting the maintenance of quality care during the pandemic.


Adjusted inpatient mortality of AIS was similar between pre- and during COVID-19 periods (4.8% vs. 5.2%; odd ratio 1.05, 95% CI 0.97-1.13), consistent with prior published studies (5,7). Also, in these adjusted models, no significant differences were observed for other outcomes such as symptomatic intracranial hemorrhage among IV alteplase patients, venous thromboembolism or pulmonary embolism during hospitalization.

In terms of patients’ disposition, there were reduced odds of discharge to skilled nursing facility (OR 0.78, 95% CI 0.74-0.82) and of a hospital stay >4 days during COVID-19 time period (OR 0.84, 95% CI 0.81-0.87), and increased odds of discharge to hospice (1.12, 95% CI 1.03- 1.21), and to home (OR 1.12, 95% CI 1.09-1.16) during COVID-19 period. These possibly reflect a hesitancy towards prolonged hospital stays, competing pressures on beds and skilled facilities, and tendency to triage away from high-risk environments.

Sensitivity analyses:

Apart from a slightly longer, and perhaps clinically insignificant, time from door to endovascular treatment in the later during COVID-19 group, findings remained largely similar in sensitivity analyses comparing those presenting in the later COVID-19 time period to those presenting pre-COVID-19.


Given its retrospective, observational nature, this study is limited in its ability to only evaluate, but not infer causality, with descriptive statistics performed being hypothesis generating. Not all data were complete and the observed decline in AIS patients during the pandemic may be due to lags in data entry. Furthermore, these findings may not be generalizable to hospitals that differ from GWTG-Stroke and international cohorts.

Key take-home message:

Despite an observed 15.3 % average decline in AIS presentations during the pandemic, this analysis from the GWTG-Stroke registry demonstrates preserved AIS care quality in the pre- and during COVID-19 time periods with similar door to needle, and door to endovascular times, similar rates of IV alteplase therapy, endovascular therapy, and adjusted in-hospital mortality.

For more latest science on Stroke and Neurology, be sure to register and attend the International Stroke Conference – happening now!


  1. Srivastava PK, Zhang S, Xian Y, et al. Acute Ischemic Stroke in Patients With COVID-19: An Analysis From Get With The Guidelines–Stroke. Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034301
  2. Ormseth CH, Sheth KN, Saver JL, Fonarow GC and Schwamm LH. The American Heart Association’s Get With the Guidelines (GWTG)-Stroke development and impact on stroke care. Stroke Vasc Neurol. 2017;2:94-105
  3. Xian Y, Fonarow GC, Reeves MJ, Webb LE, Blevins J, Demyanenko VS, et al. Data quality in the American Heart Association Get With The Guidelines-Stroke (GWTG-Stroke): results from a national data validation audit. Am Heart J. 2012;163:392-8, 398 e1.
  4. Diegoli H, Magalhaes PSC, Martins SCO, Moro CHC, Franca PHC, Safanelli J, Nagel V, Venancio VG, Liberato RB and Longo AL. Decrease in Hospital Admissions for Transient Ischemic Attack, Mild, and Moderate Stroke During the COVID-19 Era. Stroke. 2020;51:2315-2321.
  5. Nguyen-Huynh MN, Tang XN, Vinson DR, Flint AC, Alexander JG, Meighan M, Burnett M,Sidney S and Klingman JG. Acute Stroke Presentation, Care, and Outcomes in Community  Hospitals in Northern California During the COVID-19 Pandemic. Stroke. 2020;51:2918-2924
  6. American College of Emergency Physicians. Public Poll: Emergency Care Concerns Amidst COVID-19 https://wwwemergencyphysiciansorg/article/covid19/public-poll-emergency care-concerns-amidst-covid-19. 2020.
  7. Tejada Meza H, Lambea Gil Á, Sancho Saldaña A, Martínez-Zabaleta M, Garmendia Lopetegui E, López-Cancio Martínez E, et al; NORDICTUS Investigators. Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain. Eur J Neurol. 2020;27(12):2491-2498.


“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.”


Hindsight 2020: Lessons From a Calendar Year of COVID

This month signifies a full calendar year since the covid-19 pandemic has been declared a crisis and activated a worldwide response. To be exact, the WHO declared covid-19 a pandemic on March 11th, 2020. Of course, the signs were there beforehand. Starting in December 2019, there were officials in China focusing their attention on the city of Wuhan, where a flu-like disease was spreading in a cluster linked to a specific local market. By January 2020, reports of first deaths and first confirmed cases outside of China started to pop up around the world. And in early February, the news about clusters in France, Germany, cruise ships and more, should have made it clear (in retrospect) that we have a global infectious disease spreading around us. It took the world another 5-6 weeks to actually call it a Pandemic. As of mid-March 2020, our approaches have dramatically pivoted, and here we are a year later, living (with tragic numbers of losses and challenges) in a new world.

I wanted to take this calendar-year anniversary to reflect and examine some of my early thoughts and approaches to navigating the covid-19 pandemic. I’m taking full advantage of the fact that I was afforded the ability to write a blogpost on a monthly basis here in the AHA Early Career Voice (author page) as the crisis was unfolding. Within this space of reflection, I’ll try to spotlight and share some learning moments and lessons learned, in an effort to progress and adapt to the ever-changing world I was (and still am) navigating, as an early career scientist in cardiovascular & biomedical research.

In March 2020 I wrote a blog titled “Science Communication Is The Bridge We Need”, not specifically addressing Covid-19, but the pandemic was definitely was a topic on my mind from what I was reading early last year. I wanted to share my thoughts and personal viewpoint, that echo chambers and microenvironments of news sharing are dominating the internet, and scientific facts are getting missed/lost/covered up. In hindsight, it’s pretty clear that many decision-makers and lots of folks were simply not placing the required amount of urgency and focus on the news about Covid-19 that was spreading worldwide. My two-cents back in March 2020 were that more robust science communication can help with evidence-based news information sharing. I admit I’m proud of that March 2020 blogpost, no redo needed!

By April of last year, my thinking was already shifting with regards to how the pandemic is going to affect early career advancement, and what paths may be ahead. The title of that blog post was “Future Planning in the Time of Corona”, and again, I feel good about how this blogpost holds up! The theme in that written piece was centered on the often cited political tagline “Never let a crisis go to waste”. My take was that a global pandemic is one of the few causes that can truly bring to attention plans and areas of need that a vast majority of the world population can together work on.

A month later, in May 2020 I think I was slightly too optimistic and jumping a little bit ahead of myself! The title of the blogpost was “COVID-19 Stage 2: Embracing Progress, Cautiously”, and while I’m glad I measured my wording… it is now more accurate to say that most of the globe was still in Stage 1 of dealing with the pandemic back in May of last year. In June I wrote about my year-long leadership experience in my local institute’s trainee committee, my way of taking a break from always writing about the pandemic.

By July of 2020 I noticed what we now call pandemic (or covid) fatigue, and the rising tides of anti-science sentiments that started to build up as a result of the masking and social distancing regulations that have changed from one set of recommendations to a different set of ideas within a few months (from March to July). This is why I felt the need to write “Knowledge Advances Incrementally”, a blogpost where I spotlight the main working ethos of the scientific method, which boils down to:

  • Have a question
  • Come up with a testable hypothesis
  • Run the experiment
  • Collect data and analyze results
  • Verify/validate results by replication
  • Conclude what new information you can, making sure to stay exactly within the boundaries of the experiments and data you collected.

The last thing I’ll highlight is my blogpost recapping my experience in attending and participating in the annual Basic Cardiovascular Sciences (BCVS) meeting. This was the first major conference meeting that I have previously attended in-person that switched to a virtual format. I titled that blog post “A New Way To Participate”, and in retrospect, it was one of the most instructional and useful learning experiences that summer. I discussed the advantages (and challenges) that the virtual conference format brings to early-career scientists. Additionally, I pointed out some tips and tricks on how to navigate a fully online annual meeting. Back then there were a lot of wrinkles and tweaks that we learned from, and have implemented in other virtual conferences later in the year. My overall opinion still is positive, and I think that a future that includes an in-person meeting supplemented and balanced with an online component is the best way to progress and upgrade the conference format.

My take-home message today, looking back at this full calendar-year of covid exceptional circumstances, boils down to this: Humility, empathy, and optimism for a better future are essential keys to navigating the rough waters of living through a pandemic. Take care of yourself, and if possible, be helpful to others.


“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.”


Building an academic portfolio during medical training: Part 3 – The art of reaching out

A year ago, I started a blog series about how to build an academic portfolio during medical training. After the first 2 blogs, COVID-19 hit us hard, and I felt the need to switch gears to address more pressing issues. Now that things are starting to finally move in the right direction, I thought it would be a good time to pick up where we left off.

In Part 1, I discussed why I believe that it is important for medical students and trainees to consider research collaborations outside their own institutions, and what types of research studies can be performed using this type of collaboration between young researchers. In Part 2, I expanded on the different ways you can find established multi-institutional teams of young researchers.

Once you have decided on the researchers that you would like to collaborate with and join their established teams, the next logical step in this process would be to reach out. What is the best approach to use when reaching out, and how can you maximize your chances of success? The following tips may help you achieve this (Figure*):

  • Be as detailed as possible. When reaching out, it is essential that you provide as many details as possible: who you are on the professional level (level of training, career plan, etc..), what area of research you are interested in, how novice or advanced you are in the field of research (prior experiences) and what research skills you possess (basic data collection, literature review, statistical knowledge, experience with particular software or database, etc..). The more details you provide, the more likely it that you will receive a favorable response to your request. It also ensures that you join a team that constitutes the best fit for your career goals, and increases the likelihood of this collaboration being productive.
  • Be honest. As much as it is important to present yourself in the best possible way, it is even more important, to be honest about what you are able or not able to do, and what you are willing to learn. One of the crucial aspects of collaboration is reliability.
  • Don’t be afraid of presenting ideas. If you happen to have some research ideas that you would like to pursue, don’t be afraid of bringing them up on your first contact. You don’t have to provide all the details of what you have in mind, but simple broad lines about some of the areas that you would like to explore may help the person you are contacting in evaluating the utility of potential collaboration.
  • Ask about what the team needs. If you are really serious about joining a specific research team, it may be a good idea when you first reach out, to inquire about the skillsets that the team is currently looking for in a collaborator. This not only shows how dedicated you are but increases the likelihood of having a productive collaboration.
  • Reach out to more than one team/ person. Research is a very dynamic process, and at any given time a certain team may or may not have an ongoing project with room for additional collaborators. Therefore, reaching out to more than one team is a reasonable approach to avoid a long waiting time before embarking on your first project.
  • Circle back. For the same reason mentioned in the prior comment, it is common that you will receive a response like “we would be happy to collaborate, but we don’t currently have a new project for you to join”. Don’t take this as a polite rejection, because it usually is not. Circle back in a couple of months and ask nicely if the situation has changed. In the meantime, you may use tip #4 to make use of the waiting time in a way that shows dedication and improves your portfolio.

Importantly, keep in mind the general rules for teamwork. As much as teams are looking for someone who is valuable and resourceful, they are also looking for someone who is easy to work with. Being professional, collegial, hard worker, flexible and enthusiastic always goes a long way!

Figure created with BioRender.com



Johnson & Johnson COVID-19 Vaccine

On February 27, 2021, the Johnson & Johnson COVID-19 Vaccine has been Authorized by the FDA for emergency use. Which makes it the third vaccine to be authorized in the United States. The emergency use authorization was granted after 43,783 participants (18 years of age and older) with no evidence of prior COVID-19 infection were randomized to the vaccine group versus the placebo (saline) group. The trial was conducted in eight countries across three continents with a diverse and broad population. Overall, the vaccine was 66% and 67% effective in preventing moderate to severe/critical COVID-19 occurring after 2 and 4 weeks respectively. Moreover, it provided a 77% and 85% in preventing severe/critical COVID-19 occurring after 2 and 4 weeks respectively. Similar to the other vaccines, the most commonly reported side effects were pain at the injection site, headache, fatigue, muscle aches, and nausea. It is still unclear whether the vaccine will decrease transmission of the virus. Additionally, the participants were only followed up for a median of 8 weeks, so long-term efficiency or safety is not available. One of the main advantages of this vaccine is that it is administered as a single shot.

In contrast to the Pfizer and Moderna vaccines which utilized messenger RNA. Johnson & Johnson’s vaccine used existing technology to add the gene for the COVID-19 spike protein to a modified Adenovirus. After receiving the vaccine, the body will be able to produce the COVID-19 spike protein to trigger the immune system to mount an immune response without causing the disease.

(Figure from Livingston EH, Malani PN, Creech CB. The Johnson & Johnson Vaccine for COVID-19. JAMA. Published online March 01, 2021. doi:10.1001/jama.2021.2927)

Although the Pfizer and Moderna Vaccines are very effective. Having an additional vaccine will accelerate the vaccination speed. Johnson and Johnson has begun shipping its COVID-19 vaccine and expects to deliver enough single-shot vaccines by the end of March to enable the full vaccination of more than 20 million people. Additionally, Merck will be manufacturing this vaccine which will ramp up the production speed. So far, more than 50 million people have received at least one dose of the vaccine. It is expected that by the end of May 2021, vaccines will be available for the entire adult population in the United States. For the time being, we have to practice social distancing, wear a mask, and hope for the best!


1) Livingston EH, Malani PN, Creech CB. The Johnson & Johnson Vaccine for COVID-19. JAMA. Published online March 01, 2021. doi:10.1001/jama.2021.2927




“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.”



Interview with Dr. Shlee S. Song, Director, Comprehensive Stroke Center at Cedars-Sinai

Almost one year since COVID19 was deemed a pandemic, we are nowhere close to get it under control. Although it has affected the healthcare system in innumerable ways, stroke management has been particularly impacted. Not only by the disease itself, but also by the multidisciplinary and strictly protocols for its diagnosis and treatment that have been difficult to maintain for the past year. To understand the impact of COVID19 on stroke management, Dr. Shlee S. Song, the Director of the Comprehensive Stroke Center at Cedars-Sinai shared with me her experiences, and learnings through these unprecedented times.

Dr. Shlee S. Song, Director of is a board-certified vascular neurologist who completed her clinical and research fellowship at the National Institutes of Health. She has worked on steering committees and served as PI on multiple national and international multicenter stroke clinical trials.  She serves as Medical Director of Stroke Programs at Cedars Sinai, Torrance Memorial, and Marina del Rey hospital, affiliate sites of Cedars-Sinai, and has developed a telemedicine network that delivers acute stroke care, oversees stroke quality improvement, and clinical trials enrollment across network hospitals. As the previous program director for the vascular neurology fellowship program at Cedars-Sinai, she has trained many stroke neurologists that practice across the country.

MDQC: Dr. Song, what is the association between COVID19 and Stroke?

Dr. Song: So far, we know that COVID has been associated with an inflammatory state and hypercoagulable state. Patients with more severe COVID symptoms also develop cloths in both lungs and other end organs. When we had our initial surge in the spring months in 2020, we had avoided what our NY colleagues have seen, like large vessel occlusion (LVO) in young patients. However, we did see a surge since the end of November. We have had a case series of patients where they were young, without many comorbidities, but had large cloths in large vessels like the ICA and carotid.

MDQC: So, is there an association between COVID severity and stroke?

SS: Right, what I have seen so far is that patients may have one risk factor or a couple, whether it is on birth control, having hypertension, or diabetes, even if they are managing their risk factors well, a COVID infection tips the scale toward clotting. Maybe a 2 or 3 hit hypothesis, where if you have the individual risk factors you are not in an inflammatory state, you can manage them, but when the infection occurs, the other diseases set off this cascade of injury that we see.

MDQC: Has the standard of care for management for patients with stroke has changed during the pandemic?

SS: We have seen that during the pandemic, that we have to be flexible. With the demand so high for stabilization, the surge in patients to the ICU, and hospital systems being stressed, our usual stroke pathways are not available. The patients are spread out all over the hospital because the beds are hard to come by. We have to be able to train a lot of our other service line team members to be able to deliver emergency care and monitoring.

For example, sometimes, the patients cannot go to the Neuro ICU, our usual pathway. Sometimes they are going to the PACU, where the personnel might not have received that training to get the NIH stroke scale done. However, we are focusing on the things we can monitor in more severe COVID. ICU patients that require high ventilation settings have to be paralyzed, so it doesn’t make sense to do no an usual neuromonitoring ( antigravitational strength, speech, etc.), but we can do other things like checking the pupils. We have had to shift our thinking and pivot to tailor to our situation.

Right now, we are in the “stabilization mode.” We are no trying to plan a 3-6 12 follow-up because, before the pandemic, we were able to stabilize our patients quickly. However, right now, it takes longer to stabilize these patients because of the injury to their lungs. We are just trying to get patients through to the first one or two weeks and then talk about lipid-lowering and secondary prevention that can be addressed later on. Right now, we want them to survive this cascade and storm that is going on.

MDQC: Would you consider changing the mindset of strict diagnostic and treatment protocols for stroke has been the most significant challenge during the pandemic?

SS: I think there is an acknowledgment from our specialist, that are in the frontline, that we have to be flexible because we are all operating in the dark, but we are realizing collectively that we are dealing with such limited data, this is so new in terms of what we are experiencing.

Acknowledging that there is limited data allows us to focus right now on acute stabilization and realize that somethings can be done down the road. We are working on that standardized protocol to promote this mindset to streamline the process, so during night calls, there would be some guidance focused on stabilizing the patients when there is a limited team.

MDQC: Since stroke is an acute event, what has the hospital done to procure the healthcare personnel’s safety when a patient comes to the ER with an acute stroke regarding their COVID19 status?

SS: We are minimizing the amount of exposure to our team members. Since we are a small team, we want to preserve everyone’s safety. We have incorporated our telestroke robot in our emergency department (ED). Our stroke team nurses’ expertise is well-versed in maneuvering and is quick at getting their images done and answering the inclusion/exclusion criteria for thrombolytic criteria. We can see the ER with the robot’s camera. Although we agree that is this is not equivalent to see the patient at the bedside, we are aware that we oversee a system where our stroke neurologist covers multiple hospitals, not only Cedars-Sinai.

Everyone has the personal protective equipment (PPE) ready in their backpacks, our gown, N95 masks. In the setting of a stroke code, anything can happen, sometimes the patients’ airway gets compromised or has a seizure; while this happens, we can quickly gear up since we have it with us. Our pharmacies will now have 24-hour coverage as an additional help to stabilize these patients.

The rapid COVID19 test is available. We try to do it as early during the code if we suspect an LVO, so that information can be available to the IR colleagues who can be prepared. They are also assuming that many of our patients are COVID positive. However, suppose we don’t have the test results. In that case, we don’t delay the emergency recanalization procedure, if the patient is eligible, so we assume they are positive or suspected for Covid, and we gear up properly.

MDQC: What is the impact telestroke has had in managing stroke during the pandemic? And how do you think It will evolve in the years to come?

SS: Telemedicine and telestroke are here to stay. It has been around for decades. We started our program of telestroke in 2016 for covering Torrance Memorial Hospital, and the demand keeps growing. Every minute counts in the setting of a stroke code. It doesn’t make sense for someone to start driving to a hospital when we have a camera that can quickly help guide our ER or ICU colleagues.

Dr. Song, pictured on the monitor, practices treating a stroke patient remotely with other members of the care team.

The technology has been around for a while. It continues to improve, like being able to see the imaging, PAC access, able to quickly document assessments, and write the recommendations that can be seen by the team members that are accepting patients in the ICU. The technology is being improved regularly, the software, and hardware, such as upgrading the camera or reducing background noise.

One thing that I have seen during the pandemic in telestroke where I would like to see some improvement in our non-speaking English patients. Especially with the pandemic and the no-visitor policy of many hospitals, out of a concern for community spread. It’s been challenging to get accurate clinical history from our patients. We rely on witnesses from the family and relatives to determine their medication, clinical history, and bleeding risk. All of that information is difficult to get, especially if we don’t get translators in the room. If Telemedicine could get paired with translator services, so they could be available during the stroke codes, I think that would help move things along from us.

MDQC: This is especially problematic given that the Latinx population has been affected disproportionally.

SS: Yes, we saw that in our data as well. We have a paper submitted right now (REFERENCE), looking at the nine-stroke comprehensive centers in Los Angeles. We saw a disproportional amount of Latinx community affected with LVO going to our colleague hospitals, and they have noticed a sharp increase in their thrombectomy volume during the pandemic.

MDQC: Why is the Latinx community disproportionally affected?

SS: We are trying to figure out what the patient profile looks like for that cohort. We don’t know exactly; however, some theories, such as having type 2 diabetes, maybe factor in the clotting cascade in patients with COVID. Additionally, the situation with multigenerational housing and the high prevalence of essential workers within this community don’t allow them to shelter at home because they still need to go to work. These factors have been considered to contribute to stroke, but there is no known causal relationship to date.

MDQC: Nonetheless, the social determinants play a massive role in the LatinX community.

SS: Yes, and we have been seen this in feedback from our patients. For many patients getting their health maintenance evaluation is hard since they have not had their medication for HTA, DM, etc. Chronic diseases are not being controlled. Some of them haven’t seen their doctors since most clinical visits have moved to Telemedicine, which is contingent on having a computer and Wi-Fi.

In a community with many living in multigenerational households, the computers and internet might be limited resources. Sometimes they only have one computer that must be shared, for example, with kids, for distance learning, and they don’t have other devices to schedule their appointments. COVID has highlighted the gaps between the patients with more resources and those lacking them.

MDQC: We assume that everyone has a computer and good internet access, and unfortunately, that is not the reality. A pillar of medicine is the hands-on training for medical students, residents, fellows. What changes have occurred to guarantee appropriate learning during the pandemic?

SS: We have taken this opportunity to push our trainees’ telemedicine skills in the neurology residency program. Before the pandemic, we had separated telestroke training only for the fellow because we wanted the residence to have that bedside experience first before going to the telemedicine platform. We quickly realize that this skill set needed to be incorporated into the curriculum.

We wrote a paper about that and published it in Neurology, with Dr. Alicia Zha from the University of Texas and colleagues from the University of Utah.1 We have incorporated Telemedicine for the residency program. Using the telemedicine robot, our residents are directing the camera and maneuvering the robot. We also have the capability called multi presence where the attending and fellow can see what the resident is doing, so we can all see what the host resident is doing, and we can easily take over if we need to. Having this tool has been helpful and flexible. It allows the trainee to develop these skillsets for this technology that is here to stay. Other things that have improved since the pandemic are reimbursement since now Medicare allows the Telemedicine encounters to be equivalent to the side delivery of care. It has been helpful to continue to implement Telemedicine in our practice.

MDQC: So, is this being implemented just for acute stroke?

SS: The residents are using Telemedicine for the clinical encounters since we realize the virtual space is safer for both our patients and the provider. We moved much clinical evaluation to the iPad or evaluated with the desktop computer. It is also good to identify the gaps with Telemedicine, such as the subtle things with weakness and coordination we might not be able to pick up, which is very hard over the camera. Our residents are finding with their experience that things like visual fields cannot be done well with the equipment that we have right now. It’s important to know where our current gaps are so that this generation helps to problem-solve these issues to create apps or more tools to develop better telecare.

MDQC: Another colossal problem regarding stroke is the increase of the delay from symptom onset to arrival to the hospital. What has been your experience at Cedars-Sinai regarding this phenomenon?

SS: On the study with the nine-stroke comprehensive centers, we have seen that. Collectively we all had a decrease in our thrombolytic treatment patients, and IV tPA numbers have gone down, mostly the mild symptomatic patients. I think many patients and their family members are fearful. They have heard the system is currently overloaded and might think that their symptoms are very mild and not worth going to the hospital or are afraid of getting exposed to the virus. We have worked together with the AHA, Stroke association, and Los Angeles County to diffuse the message to tell people that if you have an emergency, a condition like a stroke, call 911.

Understanding patients and famile’ fear, we are trying to get patients home as soon as possible. In that streamlined workup, we intend to get patients out of this hospital as soon as possible. Suppose some things can be done outside of the hospital in the outpatient setting, then that is what we would like to do to reserve the hospital setting for the severe cases.

Some of our patients with mild symptoms when they get evaluated may have resolved their symptoms. We do urgent things for these high-risk TIA patients, such as the vessel evaluation of the carotids. However, maybe the Eco can be done in an outpatient setting, so we send the patient home with the Zio pad, telemonitoring, and have a home visit in 48-72 hours. We are more flexible in the way we deliver health. Not everything has to be delivered at the hospital, understanding patients’ fear and wanting to get home as soon as possible.

MDQC: Burning out syndrome has been a pressing issue in healthcare personnel even before the pandemic, how are you doing Dr. Song? and how are you and your peers coping with the stress this pandemic has caused?

SS: In terms of how we are manning with this crisis scenario is leaning on each other more. We have weekly check-ins, we called it our “stroke team huddles”, we have always had it because we have a very stressful job. We deal with patients and family members in a moment of crisis, are life and death situation during many of those codes, and now we are seen a lot more death.

Now there are lot more patients sicker, and we are seen more distress because they can’t have at the bedside their loved ones. How we have been dealing with ourselves? is giving each other the space to share that level of stress, so it is not something they are holding on to, but a shared collective, living process.

We have noticed that everyone has their highs and lows at different times, so we take advantage of that. The person who is doing well that day, really reaching out to say, “hey, unload a little bit, let me hear what is going on,” and for the person who is having a tougher day. Another really helpful thing has been laughter and sharing when we see something very funny; it has been really helpful to get us through. Sometimes we have to say what we are going through is so ridiculous, and just calling it out has relieved the tension when you share it, and I see it in the body language. It seems to lift from a burden and seems more relaxed.

We have counselors on checking areas, we have resources from Cedars, and if I see that something is helpful, I share it. I have been very open on how I’m getting through this crisis, either with therapy, with zoom check in with girlfriends, who are also experiencing high stress levels at home and work. All those coping mechanisms help and just check in with the clinic patients.

I have been writing letters and have encouraged residents and nurses to write letters to the patients and check in on them, especially those at higher risk because they live alone. You reach out to them, and they also give back to you and often ask how we are doing to the doctors, nurses. We are taking care of each other through this; the key is that we have each other, and we have a team approach.

MDQC: As the last question Dr. Song, what lesson have you learned from ongoing this pandemic?

SS: Lots of lessons. It has helped to solidify for me that we are doing meaningful work. In our team members, we are focusing more on what’s important and letting go of what is not. Our energy stores are getting depleted faster. We are learning to let go easier, focused on important things, and getting rid of the noise that doesn’t allow us to do so. Now we are getting more efficient in our work.

Also, we have all collectively seen that we need to do better, especially for our community areas where resources are lacking. There is a lot of goodwill and recognition in the stroke community. When it comes to leadership, we have to improve healthcare disparities. We are so grateful to the essential workers working delivering packages, in groceries, and getting us through the pandemic. They are the mail carriers, cashiers, all the people that have helped society keep moving during this pandemic. We need to give back to them.


Dr. Shlee Song shared that the pandemic has highlighted the consequences of an unequal healthcare system. We must strive to address this pressing issue as vehemently as finding new interventions or drugs. That flexibility and adaptation have been paramount to get through the pandemic. However, most important of all is teamwork, to rely on each other to provide the best care to patients and take care of each other.



  1. Zha AM, Chung LS, Song SS, Majersik JJ, Jagolino-Cole AL. Training in Neurology: Adoption of resident teleneurology training in the wake of COVID-19: Telemedicine crash course. Neurology. 2020;95(9):404-407.

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