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Frequently Asked Questions on COVID-19 in Special Populations and Patients With Comorbidities

Vikramjit Mukherjee, MD
Paul E. Sax, MD
Lynora Saxinger, MD, FRCPC, CTropMed
Dr Wong Chen Seong
Released: July 8, 2020

Questions & Answers

Should patients with diabetes and COVID-19 be treated with corticosteroids?

Short Answer: Yes, but glycemic control is challenging

Lynora Saxinger, MD, FRCPC, CTropMed (9/15/20):

We might find out more from the current trials, but so far, we do not have enough data on steroid use in patients with diabetes and COVID-19. However, people with diabetes have an enhanced risk of severe outcomes.[Bode 2020] Therefore, I provide dexamethasone to patients requiring oxygen who have progressive COVID-19, but it creates challenges for glycemic control.[Rayman 2020] This results in an increased healthcare resource burden because of increased monitoring. Regardless, I still offer steroid therapy and do enhanced monitoring for patients with diabetes who are hospitalized and require supplemental oxygen.  

Is it okay to change antiretroviral therapy for patients with HIV during the pandemic?

Short Answer: If necessary.

Wong Chen Seong, MBBS, MRCP(UK), FAMS (9/29/20):
Recommendations from multiple guideline organizations, including the British HIV Association,[BHIVA] have generally recommended that HIV treatment regimens not be modified during the pandemic, especially if there are concerns about safely accessing healthcare or visiting healthcare institutions or HIV clinics. This recommendation is to reduce the need for people living with HIV to go to a clinic where the risk of being exposed to someone with COVID-19 may be high. Also, when antiretroviral therapy is changed, there is generally a need for laboratory investigations to monitor for potential adverse events and to check for efficacy of the new treatment.

Therefore, we need to be more circumspect about the decision to change HIV therapy. Obviously, if someone is experiencing virologic failure with his or her current regimen or is experiencing unacceptable adverse events/drug-related toxicities, then treatment needs to be changed as clinically indicated, and clinicians should proceed with those changes. However, if a regimen change is being considered purely for regimen simplification or other nonurgent reasons, then I think most experts would advise to defer changes to the regimen until a time when it becomes a little bit safer for patients to come back to the clinic on a regular schedule.

Of course, this recommendation can be modified somewhat based on local circumstances. In Singapore, for example, where I practice, we can sometimes leverage technological support because we have ramped up the use of telemedicine in seeing our patients with HIV. For us, any regimen changes can be done by supplying new medications via home delivery. It works if the healthcare system is set up for it. Generally, however, it is best to try to avoid regimen changes at this time unless absolutely clinically indicated. 

There have been several cases showing that patients with well-controlled HIV do not appear to have an increased risk for severe COVID-19. Could this be due to antiviral effects of antiretroviral therapy or potential mild immunosuppression protecting them from the cytokine storm?

Short Answer: It’s complicated.

Lynora Saxinger, MD, FRCPC, CTropMed (9/15/20):
This is an interesting question, but we do not have a clear answer yet. I know my patients with HIV were very concerned at the outset of the pandemic but have been reassured by most studies reported thus far. There does seem to be a strong suggestion that in people with well-controlled HIV, immune dysfunction is not severe enough to really cause excess risk of severe COVID-19. There are also some in vitro anti–SARS-CoV-2 effects of some of the antiretroviral drugs used in HIV therapy, particularly protease inhibitors. However, it is a relatively weak antiviral effect. In studies evaluating HIV antiretroviral drugs for COVID-19 treatment in patients who do not have HIV infection, they do not appear to have efficacy against the virus. This suggests that it is unlikely antiretroviral drugs are protective for people receiving HIV treatment.

The second idea mentioned in the question is an interesting one, that not all immune suppression is the same. Aside from active, uncontrolled autoinflammatory or autoimmune diseases, receipt of steroids, or treatment with active cancer therapies, which are associated with higher risk of severe COVID-19, other forms of immune-modulating therapy do not appear to be associated with increased risk of severe disease and may be associated with reduced risk.[Simon 2020; Zrzavy 2020] Of course, data on this issue will be influenced by the fact that people who are more worried about their risk because they are receiving immune-based therapies are also likely to be more careful about contracting SARS-CoV-2 infection. But even when evaluating the patients receiving certain immunomodulatory therapies who acquire SARS-CoV-2 and then require hospitalization, COVID-19 does not appear to be as severe, and there is a slight implication that some immunomodulators might protect against severe disease, possibly by that mechanism of reducing the inflammatory consequence of infection.[Zrzavy 2020] This potential association will be something to watch as more information becomes available. But my usual thought on immune suppression is that we should be careful not to lump it altogether because some of it is, obviously, more important for severe COVID-19, and some of it might even be protective against severe COVID-19. It is quite a complex area of research.

Are there any data on COVID-19 infection in people living with HIV and their disease outcomes?

Short Answer: Yes.

Paul E. Sax, MD (9/1/2020):
In a large study from the Western Cape, South Africa, HIV infection was associated with an increased risk of death from COVID-19 vs patients who did not have HIV (adjusted HR: 2.14; 95% CI: 1.70-2.70), and the increased risk was similar regardless of the level of viral or immune suppression.[Boulle 2020] A caveat to this finding is that in South Africa, people with HIV generally come from very different socioeconomic areas compared with people without HIV. Therefore, social determinants of care could potentially be different between these groups.

Other studies that have come from Europe, the United States, and Asia really have not shown any association between HIV and more adverse COVID-19 outcomes.[Blanco 2020; Mirzaei 2020; Sigel 2020; Park 2020] I am currently telling my patients with HIV that if they have stable viral suppression and immune function, then COVID-19 does not appear to pose any additional risk. They certainly do not seem to be more likely to get infected, and they likely do not have an increased risk for severe disease based on their HIV infection provided it is well controlled.

What are the latest data, or are there any, to suggest potential protection from COVID-19 with use of HIV pre-exposure prophylaxis?

Short Answer: Not yet known.

Paul E. Sax, MD (9/1/2020):
A Spanish cohort study found that people receiving HIV treatment that included tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) were less likely to be hospitalized with COVID-19 than people receiving antiretroviral therapy regimens that did not include TDF/FTC.[del Amo 2020] That observation is hypothesis-generating since tenofovir has been proposed to be a potential SARS-CoV-2 RNA-dependent RNA polymerase inhibitor based on a molecular docking study.[Elfiky 2020] A pre-exposure prophylaxis study to determine if TDF/FTC can decrease the incidence and clinical severity of COVID-19 among healthcare workers in Spain without HIV infection is underway.[NCT04334928] I think we have to wait and see. Right now, I think we have to say maybe, but probably not.

Why are children experiencing more mild disease compared with adults?

Short Answer: It’s not yet known.

Vikramjit Mukherjee, MD (5/28/2020):
As of right now, we do not know. Thankfully, there have been fewer children infected and far fewer children in intensive care compared with adults. My pediatric colleagues think that it might have something to do with underdeveloped ACE receptors in children, which may prevent SARS-CoV-2 viral particles from gaining entry into cells. What we have seen affecting children in New York now is a Kawasaki-like syndrome, but COVID-19–related acute respiratory distress syndrome is relatively rare in children.[Toubiana 2020; Qui 2020]

Are diabetes and high blood pressure considered high risk for severe disease, even if well controlled?

Short Answer: Yes

Vikramjit Mukherjee, MD (5/28/2020):
Even if they are well controlled with medication, patients with hypertension and diabetes are still at risk for more severe COVID-19 disease. From our experiences in the Bellevue intensive care unit in New York City, the major risk factors for being critically ill were being male─72% of our ICU population was male─old age, hypertension, and obesity. Investigations into the role of ACE inhibitors, which are used to treat hypertension, and the ACE receptors in COVID-19 severity are ongoing.[NCT04330300; Kai 2020] Diabetes and sleep apnea have also been risk factors for severe disease.

Other conventional risk factors, such as preexisting lung disease, would lower the cardiopulmonary reserve for battling COVID-19. A patient with chronic obstructive pulmonary disease or interstitial lung disease, which are advanced lung diseases, would be more prone to have respiratory failure from this virus.[Alqahatani 2020]

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