African Americans, Sickle Cell Disease, and COVID-19: Dispelling Myths and Addressing Facts

Dr. Lanetta Bronté-Hall
Lanetta Bronté-Hall, MD, MPH, MSPH
President
Foundation for Sickle Cell Disease Research
Hollywood, Florida

Introduction
The impact of COVID-19 on the routine management of patients with sickle cell disease (SCD) has been substantial and complex, as clinicians now need to ensure that patients receive appropriate care for SCD in balance with the challenges posed by the pandemic. In this article, Lanetta Bronté-Hall, MD, MPH, MSPH, discusses the current data regarding the prevalence of COVID-19 among patients with SCD and provides guidance on best practice on the treatment and monitoring of SCD during the COVID-19 pandemic.

Prevalence of Sickle Cell Disease and COVID-19 among Black Americans

COVID-19 Ratio In the United States, there are ~100,000 individuals affected by SCD. For Black or African Americans, that equates to 1 in 365 who are born with the disease.1

The data on COVID-19 is constantly evolving; however, we know that Black or African American, non-Hispanic persons carry a higher burden of COVID-19 than White, non-Hispanic persons and are more likely to get infected, hospitalized, or die from the disease.2

A recently presented analysis of data from the Medical College of Wisconsin’s international SECURE-SCD Registry showed that patients with SCD and who have COVID-19 have higher rates of death due to COVID-19 vs the general Black population.3 Results also showed that younger patients accounted for the majority of hospitalizations due to COVID-19 among the SCD population. By contrast, other recent data indicate that although SCD does impose additional risk of severe COVID-19 illness and hospitalization—after balancing for age, gender, and other pre-existing conditions—mortality rates due to COVID-19 between Black patients with or without SCD were not significantly different.4

There is a significant impact for COVID-19 on Black Americans because race is a risk marker for other underlying conditions, such as lower socioeconomic status, lack of access to health care, and higher risk for exposure to the virus due to occupation (the majority of Black Americans work as frontline, essential, and critical infrastructure workers).2

Disparities in health care among Black Americans

We have always known about disparities in health care among minority populations,5-7 and the COVID-19 pandemic has exposed the magnitude of the problem and uncovered myths around it. Although a higher socioeconomic status can tremendously improve someone’s access to health care, it is not the only factor affecting health outcomes, as we're seeing that even high-rank or affluent Blacks succumb to COVID-19 at a higher rate than Whites. In the past, it was reported that the outcomes of Black patients are worse because they seek care too late. That may be true in some cases; however, another important factor is how Black patients are treated when they enter the health care system. I think that sometimes when seen in the Emergency Department (ED), symptoms of Black patients get discounted and they are sent home where they get sicker or even die; White patients with similar symptoms are more likely to be admitted and watched closely. I don’t think that anyone is being outwardly racist, but institutional racism, which is ingrained in this country but not accepted by the majority population, is a factor in health care.8 It is going to take real action to address this problem and help clinicians treat everyone equally.

Management of Sickle Cell Disease during the COVID-19 Pandemic

Available treatment options for the prevention of vaso-occlusive crisis related to SCD and their use during the COVID-19 pandemic

  • Hydroxyurea was the first FDA-approved drug for SCD.9 It is primarily used to decrease the rate of painful episodes and acute chest syndrome, based on data from clinical trials.10 One challenge with hydroxyurea is that not many patients want to continue taking it, particularly adults.11 We are now seeing more pediatric use of hydroxyurea and hope that in the long-term, it reduces the need for acute care for crises and blood transfusions. The National Heart, Lung, and Blood Institute (NHLBI) has established guidelines for the use of hydroxyurea in SCD,12 and the goal of one of its top initiatives is to improve adherence.13
  • L-glutamine was approved for SCD by the FDA in 2017, and it was the first medication approved for pediatric use.14 The amino acid glutamine plays a key role in cell metabolism, including protein synthesis, chemical energy production, and antioxidant formation. Glutamine is the most abundant amino acid and it’s produced by the body, largely in the lungs, but is also sold as a supplement (L-glutamine) against infection, injury, stress, and certain diseases.15 Some reports suggest that patients who take L-glutamine respond better to COVID-19.16 Outside SCD, a clinical trial is testing whether nutritional support, such as L-glutamine can reduce the complications of COVID-19.17
  • Crizanlizumab, a P-selectin blocker, is another new SCD medication that was approved to reduce the frequency of vaso-occlusive crises in adult and pediatric patients aged 16 and older with SCD.18 The recommended dose is 5 mg/kg intravenously over 30 minutes, with a loading dose on week 0, 2, and then every month. In my practice I have ~10 patients who receive crizanlizumab, but it's too early to tell if there’s a reduction in the rate of vaso-occlusive crises. Nonetheless, clinical trial data of crizanlizumab were promising.19
  • Voxelotor is another promising SCD medication that was granted accelerated approval by the FDA.20 Voxelotor is a hemoglobin S polymerization inhibitor that depolymerizes the globin gene, allowing red blood cells to release oxygen better. It also increases hemoglobin and decreases hemolysis.21 Unlike the other approved agents, voxelotor may provide a disease-modifying approach to SCD.33-35 We had one of the first patients who received voxelotor on compassionate use. He's been taking it since 2015 at 1000 mg daily (lower than the standard 1500 mg dose because of Grade 2 diarrhea), and his hemoglobin level ranges 1 to 1.5 g/dL above baseline, so he's been doing well. We now have ~20 patients who take voxelotor. They also report gastrointestinal adverse effects and tend not to adhere to treatment. We try to work around this issue by asking patients to take the medication with orange juice, which seems to help. We have not seen a reduction in the frequency of vaso-occlusive crises yet, but two of our patients who were oxygen-dependent and received voxelotor on compassionate use no longer need daily supplemental oxygen and their baseline oxygen saturation increased after treatment. So, results have been very promising, and we are watching for long-term outcomes.

We tend sometimes to think that one drug will come out and be the panacea for SCD. Down the road, we’re more likely to encounter polypharmacy issues related to contaminant use of multiple medications. We have already seen hydroxyurea being used with all of the other drugs, as hydroxyurea was the first one approved and continues to be strongly supported by NHLBI and other researchers and clinicians. Since L-glutamine, crizanlizumab, and voxelotor are newer agents, they are rather expensive, so it can sometimes be challenging to get them approved by payers. The cost should not be a deterrent since these new drugs have been shown to substantially improve outcomes in patients with vaso-occlusive crisis.

Managing hypercoagulability in patients with SCD

SCD is considered a hypercoagulable state.22 This state is inherent, but is not related to a true clotting factor deficiency and may be related to medication use. Some of our patients had pulmonary emboli or deep venous thrombosis, requiring treatment with low molecular weight heparin, ticlopidine, aspirin, or exchange transfusions.23 However, the frequency of thrombotic events in SCD is not as high as vaso-occlusive crises.

Chronic blood transfusions for SCD during the COVID-19 pandemic

In pediatric patients, blood transfusions are often administered to those who are at high risk for stroke. We are still scheduling transfusions for pediatric patients, without any problems in the community setting (but there may have been some issues in the academic setting). In adult patients, blood transfusions are administered episodically when sharp drops in hemoglobin occur (2 grams or more below baseline accompanied by symptoms). At the start of the COVID-19 pandemic, there were some shortages in blood supply, but conditions have improved since then. As a comprehensive SCD center, we aim to provide high-quality care to help patients avoid hospitalizations and reduce the need for blood transfusions.

Screening and Treatment of COVID-19 in Patients with Sickle Cell Disease

SCD is one of the medical conditions that increase the risk of severe COVID-19.24 Following CDC guidelines, persons (including those with SCD) who have symptoms of COVID-19 (fever, cough, difficulty breathing, etc.) or who have had close contact with an individual with COVID-19 should be tested for the virus.25 PCR testing is preferred, but other methods, such as antigen or antibody tests are increasingly available.26

To protect our patients and staff and keep our facility free of COVID-19, we brought viral testing in-house. We now screen for the virus in all of our patients monthly with ID NOW COVID-19, a molecular isothermal amplification test that returns results in 5 to 13 minutes.27 We also conduct antibody screening to detect past infections. This helps our patient know their COVID-19 status, especially those who are asymptomatic, but carry the virus and can spread it.

We provide masks to all our patients. We also explain why handwashing and physical distancing are necessary to keep themselves and their families safe and how underlying conditions can influence health outcomes. We prefer the term physical distancing over social distancing because social isolation has a huge detrimental mental health impact. We also encourage all patients to get a flu vaccine.

General points of consideration in the treatment of COVID-19 in patients with SCD

Working with Boston University, we found that the severity of COVID-19 in patients with SCD can be assessed by monitoring their signs and symptoms. Some patients are completely asymptomatic while others show signs of lung infection. Patients who are asymptomatic, but have a positive PCR/antigen test are asked to isolate at home, following CDC guidelines.28 However, we’re learning that isolating at home is often a challenge for patients from minority populations, so we ask about their home environment. If needed, we direct patients to available assistance from community resources or a COVID-19 hotel.

We start a treatment protocol if the patient’s temperature is greater than 101˚F or oxygen saturation is less than 90%. The Boston Medical Center (BMC) treatment protocol for COVID-19 in patients with SCD recommends hydroxychloroquine (400 mg twice daily on day 1, followed by 200 mg twice daily for 4 days). Remdesivir is also recommended, particularly in patients with a lung infection, because it seems to shorten the time to recovery in hospitalized patients.27 The BMC protocol recommends a 5-day regimen for remdesivir (200 mg on day 1, followed by 100 mg daily for 4 days). A 10-day regimen of remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for 9 days) was recently reported in The New England Journal of Medicne.29,30 As we learn more about COVID-19, treatment protocols are constantly being updated.31,32

Following discharge from the hospital, we stay in close contact with our patients by telemedicine visits. We monitor their signs and symptoms, and if their condition worsens, we see them in person to decide if hospitalization or more aggressive treatment is needed.

Conclusion

During the COVID-19 pandemic, patients with SCD should be encouraged to follow their usual SCD management plan. Since patients with SCD are at greater risk of severe COVID-19 infection, it is thus important to educate them on the importance of wearing masks, maintaining physical distancing, and handwashing. Patients who have symptoms of COVID-19 or who have been in close contact with individuals with COVID-19 should be tested. Patients with SCD who test positive for COVID-19 should be monitored for signs and symptoms of the infection, as this can indicate the severity of COVID-19. Asymptomatic patients should be asked to isolate at home or at community resources or COVID hotels if available, if the home environment is not conducive to self-isolation. For symptomatic patients (temperature is greater than 101˚F or oxygen saturation is less than 90%), a treatment protocol such as the BMC protocol should be initiated. Following discharge from the hospital, the patient should continue to be monitored via telemedicine.

Clinical trials and registries on COVID-19 and SCD

Educational resources for patients with SCD

References

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  2. CDC. COVID-19 Hospitalization and Death by Race/Ethnicity. 2020a. Accessed November 16, 2020, https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-race-ethnicity.html#footnote01
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