Risk Factors for Hospitalization in People With HIV and COVID-19

To the Editors:

BACKGROUND

The first cluster of a novel respiratory illness, now known as coronavirus disease 2019 (COVID-19)caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, was reported by Chinese authorities on December 31, 2019.¹ The World Health Organization declared a global pandemic on March 11, 2020,² and more than 4 million deaths have been attributed to COVID-19 worldwide to date.³

There remains debate about the clinical interaction between HIV and COVID-19. Some studies have shown similar or better COVID-19 outcomes among people with HIV (PWH) compared with individuals without HIV.^4–8 Other studies have found that lower CD4 lymphocyte counts and untreated HIV have been associated with worse outcomes,^9–12 and in at least one study, worse outcomes among PWH were driven exclusively by patients with suppressed viral load.¹³ Reviews have concluded that individuals with well-controlled HIV are not at risk of worse COVID-19 outcomes but have suggested that more evidence is needed regarding the role of HIV control on COVID-19 outcomes.^14–16 In many studies, numbers of patients evaluated have been relatively small and risk of hospitalization has not been well studied, but current guidelines state that PWH seem to be at increased risk of severe outcomes with COVID-19 compared with people without HIV.¹⁷

In this study, we describe a cohort of PWH with COVID-19 and assess predictors for hospitalization and hospital length of stay.

METHODS

We retrospectively reviewed 206 cases of individuals with HIV and SARS-CoV-2 at the 2 largest HIV care centers in Colorado: UCHealth, the academic health care system of the University of Colorado, and Denver Health and Hospital Authority, an integrated, public safety net institution serving the City and County of Denver.

Individuals aged 18 years and older were included in the study cohort if they were identified as PWH who had confirmed SARS-CoV-2 infection at the participating institutions between March 2020 and February 2021. Patients who receive their HIV care at these 2 institutions but who were SARS-CoV-2–tested or admitted for COVID-19 management at other institutions were excluded. Individuals with incidental COVID-19 admitted for non-COVID-19–related reasons were also excluded.

Electronic medical records were reviewed to collect demographic variables, indicators of level of HIV control, tobacco use, underlying medical conditions (diabetes, chronic pulmonary disease, chronic kidney disease, cardiac disease, hypertension, and mental health diagnoses), and COVID-19 outcomes (hospitalization, intensive care unit admission, length of stay, and hospital disposition). Hospitalizations not related to COVID-19 were not considered a COVID-19 outcome.

Descriptive statistics were used to characterize both hospitalized and nonhospitalized cases of COVID-19. Logistic and linear regression models were used. Univariate analyses assessed for predictors of hospitalization and log-transformed hospital length of stay, measured in days. Each variable was assessed separately in univariate models, and variables found to be significantly associated (P < 0.05) in the univariate models were included in multivariable regression models.

Study data were stored in REDCap (Research Electronic Data Capture, Vanderbilt University, Nashville, TN). Statistical analyses were conducted using SAS/STAT software, version 9.4 (SAS Institute Inc, Cary, NC). This study was approved by the Colorado Multiple Institutional Review Board.

RESULTS

Of the 206 cases of individuals with HIV and SARS-CoV-2 reviewed, 40 (19%) were excluded from analysis because they were incidentally positive for SARS-CoV-2 on surveillance testing. One hundred sixty-six individuals with HIV and SARS-CoV-2 infection were included in the final analyses. The mean age was 47 years (SD 13 years); most of them (83%) were cis male; 14% was cis female; 3% was non cis-gender; 37% was non-Hispanic White, 17% was non-Hispanic Black, and 32% was Hispanic/Latinx. In this cohort, 43% was insured by Medicaid and 42% commercially insured.

Most of them (90%) had suppressed HIV-RNA levels (≤200 copies/mL), and 10% had a CD4 lymphocyte count <200 cells/µL. Approximately 97% of individuals was on antiretroviral therapy. The most common comorbidities were mental health diagnoses (43%), hypertension (30%), and chronic pulmonary disease (18%).

Of the total cohort, 44 (27%) individuals were hospitalized with a COVID-19–related admission and 10 (23% of those hospitalized) were admitted to the intensive care unit. There was one known death among this cohort, and 86% was discharged to their previous residence, whereas 14% of individuals was discharged to a long-term care facility.

In univariate analysis, older age, lower CD4 lymphocyte cell count, and increasing number of comorbidities were significantly (P < 0.05) associated with hospitalization (Table 1). In the multivariable logistic regression model, odds for hospitalization increased by 1.23 times for every 100 cell/µL decrease in CD4 lymphocyte count [95% confidence interval (CI): 1.08 to 1.41, P < 0.01]. For every additional comorbidity, the odds of hospitalization increased 1.92 times (95% CI: 1.33 to 2.77, P < 0.01). Age was not significantly associated with odds of hospitalization in multivariable logistic regression (OR = 1.28, 95% CI: 0.92 to 1.78, P = 0.15).

TABLE 1.

Logistic Regression Models for Hospitalization Among 166 Individuals With HIV Diagnosed With COVID-19 Between March 2020 and February 2021

	Univariate		Multivariable
	OR (95% CI)	P	OR (95% CI)	P
Age (per 10-year increase)	1.61 (1.21 to 2.14)	<0.01	1.28 (0.92 to 1.78)	0.15
Race/ethnicity
Non-Hispanic White	Ref	—
Other	1.23 (0.60 to 2.52)	0.58
Sex
Cis male	Ref	—
Cis female/transgender/other	1.09 (0.44 to 2.69)	0.85
Primary language
English	Ref	—
Other	1.95 (0.79 to 4.81)	0.15
Body mass index
Underweight/normal	Ref	—
Overweight/obese	0.80 (0.39 to 1.64)	0.54
CD4 count cells/mm3 (per 100 cell decrease)	1.21 (1.06 to 1.37)	<0.01	1.23 (1.08 to 1.41)	<0.01
HIV-1 RNA
≤200 copies/mL	Ref	—
>200 copies/mL	2.27 (0.79 to 6.54)	0.13
Tobacco user
Former/never	Ref	—
Current smoker	0.51 (0.18 to 1.42)	0.20
Comorbidity count (per increase of 1)	1.72 (1.30 to 2.28)	<0.01	1.92 (1.33 to 2.77)	<0.01

Each variable was added separately in the univariate models, and the variables that were found to be significantly associated with hospitalization (P < 0.05) in the univariate models were included in the multivariable models.

Among individuals with COVID-19–related hospitalizations (n = 44), only older age and CD4 lymphocyte count were significantly associated with hospital length of stay. In the multivariable model, for every decrease of 100 CD4 lymphocyte cell count/µL, length of stay increased by 12.64% (95% CI: 3.04 to 23.15, P < 0.01), and every increase of 10 years of age was associated with 48.39% increase in length of stay (95% CI: 15.39 to 89.85%, P < 0.01).

DISCUSSION

Our findings complement the existing data on HIV and SARS-CoV-2 by including a large, diverse cohort of PWH, with both inpatient and outpatient status, from 2 distinct health care systems in the same metropolitan area. As demonstrated in other cohorts, decreased CD4 lymphocyte cell count and increased number of comorbidities were associated with increased hospitalizations, and decreased CD4 lymphocyte count and older age were associated with an increased hospital length of stay. Of importance, this analysis expanded well beyond the initial peak in COVID-19 and encompasses periods of evolving COVID-19 management options and protocols but relatively few vaccinations. Vigilance for COVID-19 among people living with HIV will continue to be critical, as will close monitoring of cases and expedited care for those with symptoms suggestive of severe disease, particularly those who are older, have lower CD4 counts, or have more comorbid conditions.