COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients

August 2021 | Volume 20 | Issue 8 | Editorials | 914 | Copyright © August 2021


Published online August 2, 2021

Katharina S. Shaw a*, Lu Yin a, Jinal K. Shah b, Rachel A. Sally a, Katerina S. Svigos a, Prince U. Adotama a, Hsiao Han Tuan a, Jerry Shapiro MDa, Rebecca A. Betensky b*, Kristen I. Lo Siccoa a*

aThe Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, NY
bDepartment of Biostatistics, New York University School of Global Public Health, New York, NY

*Both authors contributed equally to this work as co-first authors
(Katharina S. Shaw, Lu Yin) or co-senior authors (Rebecca A. Betensky, Kristen I. Lo Sicco).

Abstract
Early in the COVID-19 pandemic, anti-malarial agent hydroxychloroquine (HCQ) was touted as a potentially effective COVID-19 treatment due to its purported antiinflammatory and antiviral effects.

INTRODUCTION

Early in the COVID-19 pandemic, anti-malarial agent hydroxychloroquine (HCQ) was touted as a potentially effective COVID-19 treatment due to its purported antiinflammatory and antiviral effects. However, subsequent studies not only called the therapeutic benefit of HCQ in hospitalized patients with mild1 and severe2 COVID-19 into question, but also its efficacy as post-exposure prophylaxis (PEP) in those with known exposures.3 That said, considerable interest remains in HCQ as pre-exposure prophylaxis (PrEP), particularly in the outpatient setting. A recent meta-analysis of five randomized controlled clinical trials in which a total of 5,577 non-hospitalized (ambulatory) patients were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, postexposure prophylaxis or outpatient therapy for COVID-19 found that HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death (P=.025, RR, 0.76 [95% CI, 0.59 to 0.97]).4 While these RCTs individually yielded estimates of effectiveness of HCQ that did not reach statistical significance, the authors postulated that early study termination was a likely contributor to the absence of statistical significance. While additional randomized controlled trials (RCTs) are planned,5 we sought to investigate if HCQ confers protection against COVID-19 infection in ambulatory patients on chronic HCQ therapy prior to the onset of the COVID-19 pandemic. Thus, we performed a propensity score-weighted analysis of patients with cicatricial alopecia to identify any significant factors – including chronic HCQ use – impacting COVID-19 infection risk.

After obtaining IRB approval, we performed a retrospective chart review of patients with cicatricial alopecia who were evaluated at NYU Langone Health between 1/1/2019 and 5/1/2020 (visits in the final two months were conducted predominantly via telehealth). A total of 144 patient charts were reviewed for alopecia diagnoses, demographics, medication history and comorbidities (Table 1). Patients were contacted between 6/5/2020 and 7/1/2020 to determine whether they had developed COVID-19 infection (confirmed by PCR or antibody testing) during the initial wave of the COVID-19 pandemic in New York City, defined as 3/1/2020-5/15/2020.6

Propensity score-weighting was used to minimize bias from nonrandomized treatment assignment to HCQ (Supplemental Methods). Patients were weighted using estimated propensity scores that accounted for factors significantly associated with HCQ prescription including age, comorbid autoimmune disease and alopecia diagnosis. The main outcome of interest was COVID-19 infection. The overall cohort was 85.4% female (mean age, 57 years). Forty-five patients (31.3%) were on chronic HCQ (mean length of therapy, 56.5 months [range, 3–240 months]) including 17 of the 45 patients (37.7%) seen after 3/1/2020 via telehealth encounters.

A propensity score-weighted multivariate logistic regression revealed that patients on HCQ had a decreased risk (OR 0.87, 95% CI [0.80, 0.96]) of COVID-19 diagnosis compared to patients not on HCQ (P=0.006) after adjusting for confounders identified by LASSO selection (Supplemental Methods). Unsurprisingly, predictors of increased risk of infection included maintaining residence in New York City from March-July 2020 (corresponding to the height of the COVID-19 pandemic in New York City; OR 1.21, 95% CI [1.01, 1.23], P=0.026). Interestingly, oral antiandrogen use was not significantly associated with infection risk (OR 0.94, 95% CI [0.88, 1.01], P=0.11) despite androgenmediated SARS-CoV-2 vulnerability being cited as a potential explanation for higher rates of COVID-19-associated mortality among men (Supplemental Table 2).7

Despite using a rigorous propensity score-weighting approach