Faculty Bibliography

OBJECTIVE:To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN). METHODS:In a multicenter, randomized, open-label clinical trial, 43 patients with recurrent or refractory LN were treated with rituximab, cyclophosphamide (CYC), and glucocorticoids followed by weekly belimumab infusions until week 48 (RCB group) or with rituximab and CYC but no belimumab infusions (RC group). Patients were followed up until week 96. Percentages of total and autoreactive B cell subsets in the patients' peripheral blood were analyzed by flow cytometry. RESULTS:Treatment with belimumab did not increase the incidence of adverse events in patients with refractory LN. At week 48, a complete or partial renal response occurred in 11 (52%) of 21 patients receiving belimumab, compared to 9 (41%) of 22 patients in the RC group who did not receive belimumab (P = 0.452). Lack of improvement in or worsening of LN was the major reason for treatment failure. B cell depletion occurred in both groups, but the percentage of B cells remained lower in those receiving belimumab (geometric mean number of B cells at week 60, 53 cells/μl in the RCB group versus 11 cells/μl in the RC group; P = 0.0012). Percentages of total and autoreactive transitional B cells increased from baseline to week 48 in both groups. However, percentages of total and autoreactive naive B cells decreased from baseline to week 48 in the belimumab group compared to the no belimumab RC group (P = 0.0349), a finding that is consistent with impaired maturation of naive B cells and enhanced censoring of autoreactive B cells. CONCLUSION/CONCLUSIONS:The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN. This regimen diminished maturation of transitional to naive B cells during B cell reconstitution, and enhanced the negative selection of autoreactive B cells. Clinical efficacy was not improved with rituximab and CYC in combination with belimumab when compared to a therapeutic strategy of B cell depletion alone in patients with LN.

Background Voclosporin, a novel calcineurin inhibitor, has been tested successfully in two pivotal trials in adult patients with lupus nephritis. The Phase 3 AURORA 1 study and the Phase 2 AURA-LV study showed that compared with mycophenolate mofetil (MMF) and low-dose steroids alone, the addition of voclosporin significantly increased the complete renal response rate at approximately one year of treatment. Patients that completed the AURORA 1 study were eligible to enroll in the AURORA 2 extension study. Here we report the first interim analysis of AURORA 2. Methods AURORA 2 is a two-year, blinded, controlled extension study. Patients completing AURORA 1 continued the same randomized treatment in AURORA 2 of voclosporin (23.7 mg twice daily) or placebo, in combination with MMF (1 g twice daily) and low-dose steroids. The interim analysis evaluated urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) in patients with up to two years of total treatment. In total, 116 patients in the voclosporin arm and 100 patients in the control arm enrolled in the extension study, of which 73 patients in the voclosporin arm and 51 patients in the control arm received two years of treatment at the time of this interim analysis. Results Mean UPCR at pre-treatment AURORA 1 baseline was 3.9 mg/mg in the voclosporin arm (n=116) and 3.9 mg/mg in the control arm (n=100). The least square (LS) mean change in UPCR from pre-treatment AURORA 1 baseline to year two was -3.1 mg/mg for the voclosporin arm (n=73) and -2.1 mg/ mg for control arm (n=51; figure 1). Mean corrected eGFR at pre-treatment AURORA 1 baseline was 79.6 mL/min/1.73 m² for the voclosporin arm (n=116) and 78.9 mL/min/1.73 m² for the control arm (n=100) and at year two, was 79.0 mL/min/1.73 m² for the voclosporin arm (n=73) and 82.9 mL/min/1.73 m² for the control arm (n=51). There was a small, expected, and early decrease in mean eGFR in the voclosporin arm in the first four weeks of treatment (in AURORA 1) after which eGFR remained stable throughout year one and year two. Additionally, there were no unexpected new adverse events observed in patients who continued with voclosporin treatment compared to control-treated patients. Mixed effects model for repeated measures (MMRM) analysis of least squares mean change from pre-treatment AURORA 1 baseline for UPCR included terms for baseline covariate, treatment, visit and treatment by visit interaction. Interim analysis of AURORA 2 patients includes data from pre-treatment baseline of AURORA 1, the one-year treatment period in AURORA 1 and up to one-year treatment period in AURORA 2. Conclusions Patients in the voclosporin treatment arm maintained meaningful reductions in proteinuria with no change in mean eGFR at two years of treatment. Additional AURORA 2 efficacy and safety data will be provided at the conclusion of the study

Background Patients with Systemic Lupus Erythematosus (SLE) represent a unique population at risk for COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. This study was initiated to evaluate for the presence of SARS-CoV-2 IgG antibodies in SLE patients with and without prior COVID-19-related symptoms or COVID-19 RT PCR testing. Methods A total of 329 patients with SLE from two cohorts, one serially monitored for COVID-19 in Spring 2020 (the Web-based Assesment of Autoimmune, Immune-Mediated and Rheumatic Patients (WARCOV) and one undergoing routine surveillance (NYU Lupus Cohort) were tested for SARS-CoV-2 IgG via commercially available immunoassays processed through hospital or outpatient laboratories between April 29, 2020 and February 9, 2021. Results Overall, 16% of 329 patients had a reactive SARSCoV- 2 IgG antibody test. Seropositive patients were more likely to be Hispanic. Other demographic variables, lupus-specific factors and immunosuppressant use were not associated with reactivity. Of the 29 patients with prior RT-PCR confirmed COVID-19, 83% developed an antibody response despite 62% being on immunosuppressants. Six percent of patients who had symptoms suspicious for COVID-19 but negative concurrent RT-PCR testing developed an antibody response. Twenty-three percent of patients who had COVID- 19-related symptoms but no RT-PCR testing and 5% of patients who had no symptoms of COVID-19 developed an antibody response. Among patients initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially. In COVID- 19-confirmed patients high percentages had antibody positivity beyond 30 weeks from disease onset, 88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks. Conclusions Most patients with SLE and confirmed COVID- 19 were able to produce a serologic response despite use of a variety of immunosuppressants. These findings provide reassurances regarding the efficacy of humoral immunity and possible reinfection protection in patients with SLE

OBJECTIVE:To characterize patients with Systemic Lupus Erythematosus (SLE) affected by COVID-19 and to analyze associations of comorbidities and medications on infection outcomes. METHODS:Patients with SLE and RT-PCR-confirmed COVID-19 were identified through an established New York University lupus cohort, query of two hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web-based questionnaire and review of medical records. Baseline characteristics were obtained for all patients with COVID-19 to analyze risk factors for hospitalization. Data were also collected from asymptomatic patients and those with COVID-19-like symptoms who tested negative or were not tested. Statistical analyses were limited to confirmed COVID-19-positive patients. RESULTS:A total of 226 SLE patients were included: 41 patients with confirmed COVID-19; 19 patients who tested negative for COVID-19; 42 patients with COVID-19-like symptoms who did not get tested; and 124 patients who remained asymptomatic without testing. Of those SLE patients with COVID-19, 24 (59%) required hospitalization, four required intensive care unit-level of care, and four died. Hospitalized patients tended to be older, non-white, Hispanic, have higher BMI, history of nephritis, and at least one comorbidity. An exploratory (due to limited sample size) logistic regression analysis identified race, presence of at least one comorbidity, and BMI as independent predictors of hospitalization. CONCLUSION/CONCLUSIONS:In general, the variables predictive of hospitalization in our SLE patients were similar to those identified in the general population. Further studies are needed to understand additional risk factors for poor COVID-19 outcomes in patients with SLE.

Background/Purpose: Patients with systemic lupus erythematosus (SLE) represent a unique population in considering risk for coronavirus disease 2019 (COVID-19) with biologic, genetic, demographic, clinical and treatment issues all at play. By the nature of their chronic inflammatory autoimmune condition and regular use of immunosuppressive medications, these individuals would traditionally be considered at high risk of contracting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and having a worse prognosis. Accordingly, we aimed to characterize patients with SLE affected by COVID-19 in New York City (NYC) and analyze associations of comorbidities and medications on outcomes.
Method(s): Patients with SLE and COVID-19 (confirmed by RT-PCR testing), were identified through a longitudinal survey of an established NYU lupus cohort, query of New York University Langone Health and Bellevue Hospitals systems and referrals from rheumatologists at those institutions. All patients were age 18 or older and met SLE classification criteria or carried a rheumatologist's diagnosis of SLE. Only English-, Spanish- or Mandarin-speaking patients were included in the study. Data were prospectively collected via a web-based questionnaire and review of electronic medical records. Baseline characteristics and medications were compared between the hospitalized and ambulatory patients with COVID-19. A logistic regression analysis was performed to identify independent predictors of hospital admission.
Result(s): A total of 41 SLE patients were confirmed COVID-19 positive by RT-PCR. The patients were predominantly female and encompassed the major racial/ethnic demographics seen in NYC. The most common symptoms of COVID-19+ patients were cough (78.4%), fever (64.9%), and shortness of breath (64.9%). Of those SLE patients with COVID-19, 24 (59%) were hospitalized, 4 required ICU level of care, and 4 died, all of hypoxic respiratory failure, Table 1. Hospitalized patients tended to be older, non-white, Hispanic, and have higher BMI, antiphospholipid syndrome, a history of lupus nephritis and at least one medical comorbidity, Table 2. There was no difference between the groups in use of hydroxychloroquine, systemic steroids or immunosuppressants. Logistic regression analysis identified the following independent predictors of being hospitalized with COVID-19: race (OR = 7.78 for non-white vs. white; 95% CI: 1.13 to 53.58; p=0.037), the presence of at least one comorbidity (OR=4.66; 95% CI: 1.02 to 21.20; p=0.047), and BMI (OR = 1.08 per increase in kg/m2; 95% CI: 0.99 to 1.18; p=0.096).
Conclusion(s): Patients with SLE and COVID-19 have a high rate of hospitalization but similar mortality rate to the general population in NYC. Risk factors such as non-white race, higher BMI, and the presence of one or more comorbidities were identified as independent predictors of hospitalization in SLE patients who develop COVID-19. The use of hydroxychloroquine and immunosuppressants did not appear to influence the outcomes of patients with SLE in the setting of COVID-19. Further studies are needed to understand additional risk factors for poor COVID-19 outcomes in patients with SLE

Background/Purpose: Disparities have been reported during the coronavirus disease (COVID-19) outbreak. Systemic lupus erythematosus (SLE) patients represent a unique group that is affected by clinical, treatment, demographic, and socioeconomic (SES) risk factors for severe COVID-19 disease. The Neighborhood Deprivation Index has been associated with non-communicable disease as well as communicable disease outcomes. We conducted this study to identify neighborhood SES factors influencing SLE COVID-19 outcomes.
Method(s): Patients with SLE and COVID-19 (confirmed by RT-PCR testing), were identified through a longitudinal survey of an established NYU lupus cohort, query of NYU Langone Health and Bellevue Hospitals systems and referrals from rheumatologists at those institutions. All patients were age 18 or older and met SLE classification criteria or carried a clinical diagnosis of SLE. Baseline characteristics along with zip code neighborhood data including COVID-19 case rates and neighborhood characteristics were obtained using the Hopkins COVID database and the American Community Surveys (ACS 2014-2018) respectively. A principal component analysis was performed to identify contributory neighborhood characteristics. Then a logistic regression analysis identified predictors of testing positive for COVID-19 and COVID-19 hospitalization.
Result(s): A total of 59 SLE patients (41+ and 18-) were tested for COVID-19 by RT-PCR. The patients were predominantly female, aged 46+/-16, and racially/ethnically diverse. Roughly 140 neighborhood data points were recorded and categorized as follows: population density, race and ethnicity, household type, household size, education level, employment type and status, income and poverty, transportation method, and insurance status. COVID-19 positive patients tended to live in neighborhoods with more single parent households, households with >4 residents, higher unemployment rate, higher high school dropout rate, more public transit use, and more employment in retail, construction, and personal care services. These variables were directly proportional to principal component 1 (PC1) and accounted for 88% of the variance in neighborhood characteristics. A logistic regression model identified that PC1 (OR= 1.3; 95% CI: 1.0-1.8) and taking immune suppressants (IS) (taking vs not taking OR= 2.1; 95% CI: 1.5 to 23.3) independently correlated with having a positive COVID-19 test when controlling for hydroxychloroquine (HCQ), glucocorticoids (GC), and previous lupus nephritis (LN). Only PC1 independently correlated with COVID-19 hospitalization (OR= 1.4; 95% CI: 1.1-1.9) upon controlling for taking IS, HCQ, GCs, and LN. PC1 associated with African American (AA) or Hispanic patient race/ethnicity (OR= 1.6, 95% CI: 1.2-2.2).
Conclusion(s): In addition to SLE disease, neighborhood characteristics and SES are important risk factors both for contracting COVID-19 and developing severe disease. Neighborhood deprivation may mediate the reported relationship between AA and Hispanic race/ethnicity and COVID-19. Given that a plurality of SLE patients are of AA and/or Hispanic backgrounds, care teams must formulate strategies to address socioeconomic stress in our patients

Background/Purpose: We reported previously (Ramsey-Goldman et al., Arthritis Rheumatol 2020) that score > 0.8 of a multianalyte assay panel (MAP) with algorithm predicts fulfillment of a 4th ACR criterion 9-18 months (median 12) after enrollment in patients with probable systemic lupus erythematosus (pSLE). We continued to follow pSLE to better evaluate transition to classifiable SLE.
Method(s): pSLE, defined as fulfilling 3 ACR criteria, were followed at academic lupus centers. At enrollment, 35 (38%) of the 92 pSLE fulfilled SLICC criteria. CB-CAPs - C4d bound to erythrocytes (EC4d) and B-cells (BC4d) - were measured by quantitative flow cytometry, serum C3 and C4 by turbidimetry, and autoantibodies by ELISA. Anti-dsDNA positivity was confirmed by immunofluorescence (IFA). MAP index consists of an algorithm with CB-CAPs and autoantibodies (Dervieux et al., J Immunol Methods 2017). Initial decision analysis with Youden index showed that MAP > 0.8 and EC4d > 20 mean fluorescence intensity units (MFI) reflected the optimal cutoffs for transition to ACR classifiable SLE; the same cutoffs were used for analysis of all follow-up visits. Time to fulfillment of ACR criteria was evaluated by Kaplan-Meier analysis; associations were analyzed by log-rank test and Cox proportional hazards model and are expressed as hazards ratio (HR).
Result(s): Of the 92 pSLE, 74 had 1 or 2 follow-up visits 9-35 months after enrollment for a total of 128 visits. Overall, 28 pSLE (30.4%) transitioned to ACR classifiable SLE: 16 (57%) in the 1st year and 12 (43%) in the 2nd. The clinical or laboratory features that defined fulfillment of ACR criteria are in Table 1. Use of hydroxychloroquine and immunosuppressants was similar in those who did and did not transition to SLE. Of the 17 subjects who accrued hematological criteria during the study (11 as the sole criterion and 6 as one of the new criteria), a minority were on immunosuppressants: 6 at enrollment, 5 at the 1st visit, and 3 at the 2nd. Neither SLICC criteria nor individual biomarkers were significantly associated with transition to SLE (Table 2). Only MAP > 0.8 had significantly high HR for transition to SLE; EC4d > 20 MFI, low complement, and anti-dsDNA were not significant (Table 2).
Conclusion(s): The majority of pSLE transitioned within a year. MAP > 0.8 predicted disease evolution into classifiable SLE better than other biomarkers or fulfillment of SLICC criteria

Background/Purpose: Neonatal Lupus (NL) is a model of passively acquired autoimmunity conferred by exposure to maternal anti-Ro antibodies with major manifestations being congenital heart block (CHB) and/or cutaneous disease. This study was initiated to address the development of de novo autoimmunity in these children and identify associated clinical and genetic risk factors.
Method(s): In a retrospective cohort study of enrollees in the Research Registry for Neonatal Lupus (RRNL), 511 children exposed to anti-Ro in utero responded to a follow up questionnaire focused on symptoms of autoimmunity. Self-reported diseases were confirmed via medical record review. Bivariate analyses were performed with potential risk factors for the development of autoimmune disease (AD) and included the NL status per se, a disease severity score based on mortality risk factors, and maternal AD (inclusive of lupus, Sjogren's syndrome, psoriasis, rheumatoid arthritis, or thyroid disease). A subset of 99 CHB, 9 cutaneous, and 55 unaffected anti-Ro exposed RRNL individuals were genotyped at Class II HLA DRB1 and DQB1 four-digit alleles, which were assigned by imputation (HIBAG) or sequencing. Generalized estimating equations (logit link, exchangeable correlation) were used to test for associations between HLA alleles and the development of AD.
Result(s): Of the respondents, 182 offspring had CHB, 95 had cutaneous only NL and 234 were siblings without NL. Females comprised 53% and 80% were Caucasian. The mean age was 14.2+/-9.7; 4% age 0-2 years, 48% 2-13 years, and 47% > 13 years. An AD developed in 38 offspring (20 CHB, 7 cutaneous NL, 11 non-NL siblings; Table 1). The most prevalent AD was thyroid disease. The development of an AD was significantly associated with presence of CHB vs. cutaneous only or non-NL siblings (11% vs. 5%, p=0.033). The maternal health status did not influence the development of an AD in the child (7% mothers with AD vs. 6% asymptomatic mothers, p=0.67). Mean NL severity score was higher in offspring with AD (3.8+/-4.8 vs. 2.2+/-4.0, p= 0.031). Other markers of fetal CHB disease severity were associated with subsequent AD development, including in-utero exposure to fluorinated steroids (15% vs. 6%, p=0.088) and beta agonists such as terbutaline (23% vs. 9%, p=0.043). In the study of 163 RRNL cases with HLA data (20 with AD, 143 without), HLA DRB1*03:01 (OR 3.4, CI 1.46-7.90, p=0.0045), DQA1*05:01 (OR 3.39, CI 1.16-9.92, p=0.0262), and DQB1*02:01 (OR 4.28, CI 1.73-10.62, p=0.0017) were associated with increased risk of AD (of note, these loci are in high linkage disequilibrium). In contrast, these alleles were not significantly associated with development of CHB (99 CHB vs. 64 without).
Conclusion(s): The development of an autoimmune disease was more common in anti-Ro exposed children with CHB, greater NL severity, and MHC Class II haplotypes. These factors may relate to an inherent susceptibility to inflammation and fibrosis, occuring in utero and later in life

Background/Purpose: Belimumab (BEL) has demonstrated efficacy in systemic lupus erythematosus (SLE) in 4 positive pivotal trials. This study assessed the efficacy and safety of intravenous (IV) BEL plus standard therapy (ST) in patients (pts) with active lupus nephritis (LN).
Method(s): This Phase 3, double-blind, placebo (PBO)-controlled study (GSK Study BEL114054; NCT01639339) randomized (1:1) adults with SLE and biopsy-proven LN (class III, IV, and/or V) to monthly BEL 10 mg/kg IV or PBO, plus ST. Randomization was stratified by race and treatment regimen (high-dose corticosteroids + either cyclophosphamide followed by azathioprine, or mycophenolate mofetil [MMF] followed by MMF). Primary endpoint: Primary Efficacy Renal Response (PERR; urine protein-creatinine ratio [uPCR] <=0.7; estimated glomerular filtration rate [eGFR] no worse than 20% below pre-flare value or >=60 ml/min/1.73m2; no rescue therapy) at Week (Wk) 104. Key secondary endpoints: Complete Renal Response (CRR; uPCR < 0.5; eGFR no worse than 10% below pre-flare value or >=90 ml/min/1.73m2; no rescue therapy) at Wk 104; Ordinal Renal Response (ORR; CRR, PRR or no response) at Wk 104; PERR at Wk 52; time to renal-related event (defined in Table 1) or death. Wk 104 PERR/CRR were analyzed in subgroups: treatment regimens, LN class, race. Additional evaluations included: time to first severe SFI flare (defined in Table 2); proportions of pts with SLEDAI-S2K (defined in Table 2) score < 4 and with prednisone dose <=7.5/5 mg/day, both at Wk 104; changes from baseline in biomarkers (anti-dsDNA, anti-C1q, C3, C4) at Wk 104; safety.
Result(s): Randomized pts: 448 (efficacy: 223/group; safety: 224/group). The study met its primary and key secondary endpoints (Table 1). Risk of a renal-related event or death was lower over the study with BEL vs PBO (HR [95% CI] 0.5 [0.3, 0.8]; p=0.001). Table 2 displays additional endpoints. The odds of PERR/CRR responses at Wk 104 on BEL vs PBO were numerically greater for listed subgroups, except pure class V LN (Figure); however, in class V, a numerically greater proportion of BEL vs PBO pts achieved PERR/CRR response at Wk 52 (PERR: 44.4% vs 33.3%; CRR: 36.1% vs 27.8%, respectively). At Wk 104, in pts with baseline autoantibodies, median (IQR) percent change from baseline (BEL vs PBO) in anti-dsDNA was -74.2 (-85.1, -49.5) vs -36.6 (-69.7, 28.6); and anti-C1q was -73.2 (-84.1, -59.0) vs -57.9 (-76.1, -33.2). *p-value was from a rank ANCOVA model comparing belimumab and placebo with covariates for treatment group, induction regimen (CYC vs MMF), race (black vs non-black), baseline uPCR, and baseline eGFR. Study WD, TF, and IPD were imputed as non-responders; +defined as eGFR no worse than 10% below baseline value or within normal range, >=50% decrease in uPCR (either uPCR <1.0 if baseline ratio <=3.0, or uPCR <3.0 if baseline ratio >3.0), no rescue therapy, and not a CRR; ++defined as the first event experienced among the following: endstage renal disease/doubling of serum creatinine/renal worsening/renal disease-related treatment failure or death; Pnumber/proportion of pts reporting the event ANCOVA, analysis of covariance; BEL, belimumab; CI, confidence interval; CRR, Complete Renal Response; CyC, cyclophosphamide; eGFR, estimated glomerular filtration rate; HR, hazard ratio; IPD, investigational product discontinuation; IV, intravenous; MMF, mycophenolate mofetil; NR, non-responder; OR, odds ratio; ORR, Ordinal Renal Response; PBO, placebo; PERR, Primary Efficacy Renal Response; PRR, Partial Renal Response; TF, treatment failure; uPCR, urine protein-creatinine ratio; WD, withdrawal; Wk, Week In pts with low baseline complement levels, median (IQR) percent change from baseline (BEL vs PBO) in C3 was 43.8 (17.1, 88.9) vs 30.0 (13.5, 59.8) and in C4 was 115.5 (60.0, 177.8) vs 66.7 (22.2, 166.7). Adverse events (AEs; >=1) were reported for 95.5% of BEL and 94.2% of PBO pts; 12.9% of pts in each group had >=1 AE resulting in study treatment discontinuation. Serious AEs (>=1) were reported for 25.9% of BEL and 29.9% of PBO pts, most commonly infections and infestations (13.8% of BEL vs 17.0% of PBO pts); 1.8% of BEL and 1.3% of PBO pts developed on-treatment fatal AEs (mainly due to infections).
Conclusion(s): In this large 2-year LN study, compared with ST alone, BEL plus ST improved renal outcomes, overall SLE disease activity, and biomarker levels, while reducing steroid use, with a favorable safety profile

Background - Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine (HCQ) is being considered as prophylaxis and treatment of COVID-19. Although HCQ is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematous and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. Methods - To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal electrocardiograms (ECGs) and HCQ blood levels were available in a recently completed study evaluating the efficacy of HCQ 400mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro antibodies. Results - Forty-five ECGs were available for QTc measurement, and levels of HCQ were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of HCQ and the neonatal QTc (R = 0.02, P = 0.86) or the mean of HCQ values obtained throughout each individual pregnancy and the QTc (R = 0.04, P = 0.80). In total 5 (11%; 95% CI: 4% - 24%) neonates had prolongation of the QTc > 2SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. Conclusions - In aggregate, these data provide reassurances that the maternal use of HCQ is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered.