A Case Series of Five People Living with HIV Hospitalized with COVID-19 in Chicago, Illinois

Abstract

The risk of COVID-19 among people living with HIV (PLWH) is largely unknown and there have been very few reported cases in the literature. We report a case series of five PLWH with COVID-19. We identified all patients with a diagnosis of HIV who tested positive for SARS-CoV-2 at University of Chicago Medicine between March 1, 2020, and April 7, 2020. We retrospectively collected data regarding demographics, comorbidities, medications, laboratory test results, radiology results, and outcomes associated with COVID-19. All five PLWH with COVID-19 were African American; 80% (4/5) were cisgender females. The mean age of patients was 48 years old (range 38–53). The majority of patients presented with cough, fever, and shortness of breath. Three patients had diarrhea. One patient presented with predominantly cardiac symptoms. All were taking antiretroviral therapy (ART) with CD4 count >200 cells/mm³ and suppressed HIV viral loads at the time of COVID-19 diagnosis. All five patients were hospitalized, two required supplemental oxygen, and none required mechanical ventilation. Four patients were treated with azithromycin and a cephalosporin and two were also treated with hydroxychloroquine. The median length of stay was 3 days (range 2–7). All patients recovered. More research is needed to understand the risks of COVID-19 among PLWH and the impact of ART on outcomes for patients with COVID-19.

Introduction

The risk of COVID-19, caused by SARS-CoV-2, among people living with HIV (PLWH) is unknown. Some scientists have speculated that PLWH taking antiretroviral therapy (ART) may be at decreased risk for COVID-19 because HIV antiretroviral medications may have activity against coronaviruses such as SARS-CoV-2.¹ PLWH also may be at decreased risk for complications of COVID-19 because their defective cellular immunity may reduce the possibility of the cytokine dysregulation that is associated with severe cases of COVID-19.^2,3 Others have suggested that the opposite may be true: PLWH may be at increased risk for COVID-19 due to immunosuppression.⁴ The literature from the SARS outbreak of 2003 caused by SARS-CoV-1 provides some evidence that HIV infection is associated with a milder course of SARS and that HIV antiretroviral medications may reduce mortality and adverse outcomes from SARS.^5,6

In the United States, African Americans have been disproportionately affected by COVID-19.⁵ In majority African American counties in the United States, the COVID-19 infection rates and death rates are three and six times higher, respectively, than those of majority white counties. This may be due to a higher burden of comorbidities, poorer social determinants of health, and socioeconomic factors that make it difficult for African Americans to socially distance.⁶ African Americans are also disproportionately affected by HIV, but large studies in the United Kingdom and New York City during the early months of the pandemic have found that PLWH are underrepresented among severe COVID-19 cases.^7,8

There is very little published literature to date regarding the clinical course of COVID-19 among PLWH. Two case reports from China and a small case series from Spain have described a total of seven PLWH who developed COVID-19. All reported cases were male or transgender, few had medical comorbidities, and all recovered except for one patient who remained in the intensive care unit at the time of the report.^9–11 Data are lacking regarding the clinical course of COVID-19 among cisgender female PLWH as well as among PLWH with other comorbidities.

Methods

We identified all patients with a diagnosis of HIV who tested positive for SARS CoV-2 at University of Chicago Medicine between March 1, 2020, and April 7, 2020. This study was approved by the University of Chicago Institutional Review Board. A waiver of consent was granted as only deidentified data were extracted from the medical record. We report the cases of five PLWH diagnosed with COVID-19, including four cisgender females (Table 1).

Table 1.

Characteristics of Patients with HIV and COVID-19

Case	Age	Gender	BMI	HIV viral load (copies/mL)	CD4 count (cells/mm3)	ART regimen	Comorbidities	Peak inflammatory markers	COVID-19 therapy	Hospital LOS
1	38	M	37.4	<20	315	ABC, DTG, 3TC	DM, HTN, obesity, OSA, HLD	Ferritin 5937ng/mL HD4*	Hydroxychloroquine	4 days
								CRP 44 mg/L HD3*
								D-dimer 3.32 μg/mL HD4*
								Fibrinogen 182 mg/dL HD3
2	50	F	45.7	<20	305	BIC, FTC, TAF	obesity	Ferritin 651 ng/mL HD2*	None	3 days
								CRP 126 mg/L HD 2*
								ESR 117 mm/h HD2*
								D-dimer 0.56 μg/mL HD2*
								CK 162 U/L HD2
								LDH 315 U/L HD2*
								Fibrinogen 624 mg/dL HD2*
								IL 6 13.9 pg/mL HD3*
3	51	F	29.8	<20	265	EVG, COBI, FTC, TAF	none	Ferritin 480 ng/mL HD6*	Hydroxychloroquine	6 days
								CRP 100 mg/L HD 6*
								ESR 58 mm/h HD2*
								D-dimer 0.9 μg/mL HD1*
								CK 2468 U/L HD1*
								LDH 467 U/L HD2*
								Fibrinogen 511 mg/dL HD3*
								IL 6 35.4 pg/mL HD3*
4	53	F	17.7	25	268	BIC, FTC, TAF, RTV, DRV	bronchoesophageal fistula, Addison's disease	Ferritin 151 ng/mL HD1	None	2 days
								CRP 49 mg/L HD1*
								D-dimer 2.3 μg/mL HD1*
								CK 74 U/L HD1
								LDH 162 U/L HD1
								Fibrinogen 506 mg/dL HD1*
5	47	F	40.8	<20	500	TDF, FTC, DRV, RTV, RAL	CHF s/p ICD, CVA, PE, COPD, HTN, morbid obesity	None measured	None	2 days

^*Indicates elevated value. Normal ranges: ferritin, 10–220 ng/mL; fibrinogen, 180–409 mg/dL; CRP, <5 mg/L; D-dimer, <0.4 μg/mL; CK, 9–185 U/L; LDH, 116–245 U/L; IL 6, ≤1.8 pg/mL.

ABC, abacavir; ART, antiretroviral therapy; BIC, bictegravir; CHF, congestive heart failure; CK, creatine kinase; COBI, cobicistat; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; CVA, cerebrovascular accident; DM, diabetes mellitus; DRV, darunavir; DTG, dolutegravir; ESR, erythrocyte sedimentation rate; EVG, elvitegravir; FTC, emtricitabine; HD, hospital day; HLD, hyperlipidemia; HTN, hypertension; ICD, implantable cardioverter defibrillator; IL 6, interleukin 6; LDH, lactate dehydrogenase; LOS, length of stay; OSA, obstructive sleep apnea; PE, pulmonary embolism; RAL, raltegravir; RTV, ritonavir; TAF, tenofivir alafenamide; 3TC, lamivudine.

Results

Case 1

A 38-year-old African American cisgender male with HIV presented to the emergency department (ED) with 7 days of fever, dry cough, shortness of breath (SOB), headache, and myalgias. He also had 3 days of diarrhea. Medical history included diabetes mellitus type 2 with a hemoglobin A1C of 9.9%, obstructive sleep apnea, hyperlipidemia, hypertension, and obesity. He reported compliance with ART of abacavir, dolutegravir, and lamivudine.

On presentation, he was febrile to 39.3°C and tachycardic. His oxygen saturation was 94% on room air (RA). His laboratory results showed elevated liver function tests (LFTs) with asparate aminotransferase (AST) 477 U/L (ref. range 8–37 U/L) and alanine aminotransferase (ALT) 363 U/L (ref. range 8–35 U/L) as well as a serum glucose level of 297 mg/dL (ref. range 60–99 mg/dL). On the day of admission, he had an undetectable viral load (VL) and CD4 count of 315 cells/mm³ (ref. range 515–1642 cells/mm³). Nasopharyngeal sample for SARS CoV-2 PCR was positive, and a multiplex PCR respiratory viral panel (RVP) was negative. Chest X-ray showed perihilar patchy opacities and chest CT showed bilateral ground glass opacities. He was admitted due to evidence of viral pneumonia, elevated LFTs, and uncontrolled diabetes mellitus.

He was treated with empiric ceftriaxone and azithromycin for 5 days for possible community-acquired pneumonia (CAP). Hydroxychloroquine was started on hospital day (HD) 3, at a dosage of 400 mg po every 12 h for 2 doses followed by 200 mg po every 12 h to complete 5 days. He did not require supplemental oxygen throughout the hospital stay. He clinically recovered and was discharged on HD 5.

Case 2

A 50-year-old African American cisgender female with HIV presented to the ED with 1 week of cough productive of white sputum, daily fevers, and progressive SOB as well as 1 day of headache. She denied any sick contacts. She endorsed adherence to her antiretroviral regimen of bictegravir, emtricitabine, and tenofovir alafenamide. Her only significant comorbidity was obesity.

On presentation, she was afebrile with a temperature of 36.6°C, and had an oxygenation saturation of 88% on RA, which improved to 93% with 2 L nasal cannula (NC). She was admitted due to hypoxia. Nasopharyngeal sample for SARS CoV-2 PCR was positive and RVP was negative. HIV VL was undetectable and CD4 was 305 cells/mm³ on the day of admission. Chest X-ray showed mild multi-focal patchy airspace consolidation in the left lower lobe.

On HD 2, her oxygenation status slightly worsened and she required 3–4 L oxygen by NC. She was treated with 5 days of azithromycin and 1 dose of ceftriaxone followed by 4 days of cefdinir for possible CAP. She did not receive any therapy for COVID-19. Her oxygenation improved and she was discharged on HD 4.

Case 3

A 51-year-old African American cisgender female with HIV presented to the ED with 1 week of cough productive of yellow sputum, myalgias, SOB, 4 days of fever, and 1 day of watery diarrhea. Her only medical history was a remote history of latent tuberculosis treated with isoniazid for 9 months. She reported good adherence to her ART regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide, with most recent VL undetectable 7 months before admission, but she had missed 5 days of ART before admission.

On presentation, her oxygen saturation was 93% on RA, and she was given 2 L oxygen by NC. She was admitted to rule out acute coronary syndrome. Her temperature was 36.4°C on admission, but increased to 39.3°C the second day of admission. Nasopharyngeal sample for SARS CoV-2 PCR was positive and RVP was negative. CD4 count on admission was 265 cells/mm³. Chest X-ray showed bilateral perihilar and basilar patchy airspace and interstitial opacities.

She was initiated on ceftriaxone and azithromycin for empiric CAP treatment, with ceftriaxone transitioned to cefdinir on HD 2 to complete a 5 day course. She was treated with hydroxycholoroquine at a dosage of 400 mg po every 12 h for 2 doses followed by 200 mg po every 12 h to complete 5 days. She clinically improved and was discharged on HD 7.

Case 4

A 53-year-old African American cisgender female with HIV and a history of esophageal strictures status post stenting complicated by bronchoesophageal and tracheoesophageal fistulas presented with 1 week of nausea, vomiting, intermittent diarrhea, dehydration, and cough of productive sputum. She endorsed chills, but denied any fever. She denied any sick contacts. She reported missing several doses of her ART regimen of bictegravir, emtricitabine, tenofivir alafenamide, ritonavir, and darunavir in the days before admission, due to nausea and vomiting.

On presentation she was febrile to 39°C and had oxygen saturation of 97% on RA. She was admitted after she was found to be dehydrated and hyponatremic with a sodium of 127 mmol/L (ref. range 134–149 mmol/L). The day of admission she had a HIV VL of 24.6 copies/mL and a CD4 count of 268 cells/mm³. Nasopharyngeal sample for SARS CoV-2 PCR was positive, and RVP and multiplex PCR gastrointestinal panel were both negative. Her chest X-ray was unremarkable.

She was treated with 5 days of cefdinir and azithromycin for empiric CAP treatment. She did not require supplemental oxygen throughout her hospital stay and was discharged on HD 3.

Case 5

A 47-year-old African American cisgender female with HIV presented to the ED with 1 day of abdominal pain with nausea and vomiting, intermittent chest pain, dyspnea on exertion, and chills. She denied sick contacts. She reported she had missed the past 2 weeks of her ART regimen of tenofovir disoproxil fumarate, emtricitabine, darunavir, ritonavir, and raltegravir. Her medical history was notable for heart failure with ejection fraction of 15% with implantation of implantable cardioverter defibrillator (ICD), chronic obstructive pulmonary disease, hypertension, and morbid obesity. Five months before admission, she had a cerebrovascular accident and acute pulmonary embolism for which she was prescribed anticoagulation with warfarin.

On presentation she was afebrile and tachycardic with an oxygen saturation of 100% on RA. In the ED, she experienced an episode of nonsustained ventricular tachycardia with aberrancy after which she was admitted to the cardiac intensive care unit. High sensitivity troponin T was 30 ng/L (ref range <14 ng/L). International normalized ratio (INR) was subtherapeutic at 1.1. Her HIV VL was undetectable and CD4 count was 500 cells/mm³. On the day of admission, a nasopharyngeal swab for SARS CoV-2 PCR test was negative. Chest X-ray showed cardiomegaly but no infiltrate. Abdominal CT showed wedge-shaped splenic infarction.

A nasopharyngeal swab for SARS CoV-2 PCR was repeated on HD 3 with a positive result. Her medical providers recommended she remain in the hospital until her INR normalized, but the patient elected to be discharged against medical advice on HD 3. She returned to clinic to monitor her INR 3 days after discharge, at which point she endorsed resolution of symptoms.

Discussion

We report the first case series of PLWH with COVID-19 from the United States, of whom all five were African American and four were cisgender females. All patients had CD4 count >200 cells/mm³, were taking ART, and were virally suppressed. Antiretrovirals commonly used to treat HIV may have activity against SARS CoV-2, and are actively being studied as treatment for COVID-19. Although studies from the 2003 SARS epidemic showed a decrease in mortality, intubation rates, and adverse outcomes of SARS with the use of lopinavir/ritonavir,^12,13 a recent clinical trial showed no benefit of lopinavir/ritonavir used alone for treatment of severe COVID-19.¹⁴ Other clinical trials are ongoing, including a clinical trial of tenofovir/emtricitabine for pre-exposure prophylaxis against COVID-19 in health care workers,¹⁵ and a clinical trial of darunavir/cobicistat for treatment of COVID-19.¹⁶

Although all five patients required hospitalization, they also had a relatively mild clinical course with a median length of stay of only 3 days. Only two patients required supplemental oxygen therapy. One patient was admitted to the cardiac ICU for monitoring for ventricular tachycardia, but no other patients required ICU admission and none of the patients required mechanical ventilation. Preliminary reports from the Centers for Disease Control and Prevention show that in the United States overall, 34% of patients with laboratory-confirmed COVID-19 have required hospitalization, and among those hospitalized, 20% required admission to an ICU.¹⁷

Our patients' symptoms were consistent with previously reported clinical presentations of COVID-19 with the majority having cough, fever, and SOB.¹⁸ Three patients also reported diarrhea, consistent with other reports that up to 50% of patients with COVID-19 report gastrointestinal symptoms.¹⁹

Patient 5 presented with predominantly cardiac symptoms. Others have also reported cardiac complications associated with COVID-19, including arrhythmias and myocardial infarction.²⁰ Underlying cardiovascular disease and cardiac injury are risk factors for severe disease and associated with increased mortality.³ Our patient had mildly elevated troponin levels representing myocardial injury, but had a relatively mild clinical course of COVID-19. Patient 5 also had a splenic infarction, concerning for thromboembolic disease. COVID-19 is associated with hypercoagulability,²¹ but in this patient with low cardiac ejection fraction and a subtherapeutic INR, the cause of her splenic infarction was suspected to be a left ventricular thrombus.

Of note, Patient 5 had a negative SARS-CoV-2 PCR test on admission, but tested positive 2 days later. Others have also reported cases of false negative SARS CoV-2 PCR results early in the course of disease with COVID-19.^22,23

In this case series, all five PLWH with COVID-19 achieved full clinical recovery. More research is needed to understand the clinical course of COVID-19 among PLWH, particularly those with poor viral suppression and/or advanced immune deficiency, as well as the impact of ART on outcomes for patients with COVID-19.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.