COVID-19 in hospitalized HIV-positive and HIV-negative patients: a matched study

HIV Medicine. 2021;22:867–876. | 867 wileyonlinelibrary.com/journal/hiv Received: 19 May 2021 | Accepted: 28 June 2021 DOI: 10.1111/hiv.13145 SHORT COMMUNICATION COVID- 19 in hospitalized HIV- positive and HIV- negative patients: A matched study CristinaDíez1,2 | JorgeDel Romero- Raposo3 | RafaelMican4,5 | Juan C.López1,2 | JoséR.Blanco6 | SoniaCalzado7 | GloriaSamperiz8 | JoaquínPortilla9 | LucioJ.García- Fraile10 | FélixGutiérrez11 | Juan L.Gómez- Sirvent12 | InésSuárez- García13,14 | ConchaAmador15 | MaríaNovella16 | Jose R.Arribas4,5 | SantiagoMoreno17,18,19 | JuanGonzález- García4,5 | InmaculadaJarrín3 | JuanBerenguer1,2 | for CoRIS* 1Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain 2Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM, Madrid, Spain 3Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain 4Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain 5Instituto de Investigación Hospital Universitario La Paz (IdiPAZ, Madrid, Spain 6Servicio de Medicina Interna, Hospital Universitario San Pedro – CIBIR de Logroño, Logroño, Spain 7Unidad de Enfermedades Infecciosas, Hospital Universitario Parc Tauli, Sabadell, Spain 8Unidad de Enfermedades Infecciosas, Hospital Universitario Miguel Servet, Zaragoza, Spain 9Unidad de Enfermedades Infecciosas, Hospital General Universitario de Alicante, Alicante, Spain 10Sección de Enfermedades Infecciosas, Hospital Universitario La Princesa, Madrid, Spain 11Unidad de Enfermedades Infecciosas, Hospital General Universitario de Elche, Elche, Spain 12Sección de Infecciones, Hospital Universitario de Canarias, Tenerife, Spain 13Grupo de Enfermedades Infecciosas, Departamento de Medicina Interna, Hospital Universitario Infanta Sofía, Madrid, Spain 14Facultad de Medicina, Universidad Europea de Madrid, Madrid, Spain 15Unidad de Enfermedades Infecciosas, Hospital de la Marina Baixa, Alicante, Spain 16Unidad de Enfermedades Infecciosas, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain 17Servicio de Enfermedades Infecciosas, Hospital Universitario Ramón y Cajal, Madrid, Spain 18Facultad de Medicina, Universidad de Alcalá, Madrid, Spain 19Instituto Ramón y Cajal de Investigación Sanitaria (irycis, Madrid, Spain This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association *Members of the the Spanish HIV Research Network Cohort (CoRIS) are given in the Appendix. Funding information Instituto de Salud Carlos III Abstract Objectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID- 19 with [people with HIV (PWH)] and without (non- PWH) HIV coinfection in Spain during the first wave of the pandemic. 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 868 | DÍEZ Et al. INTRODUCTION Since the beginning of the COVID- 19 pandemic, HIV has been uncommonly listed as an underlying condition in case series of hospitalized patients with COVID- 19 [1, 2]. This is likely because of the much lower prevalence of HIV among the general population than that of other prevailing diseases and because the number of older individuals is much lower among people with HIV (PWH) than among the HIV- uninfected population (non- PWH). Notwithstanding this, whether HIV increases the risk of acquiring SARS- CoV- 2 or the severity or mortality of COVID- 19 has stirred substantial research. Many studies have analysed the characteristics and outcomes of COVID- 19 in PWH, but to the best of our knowledge, only in eight of these has some comparison been made between PWH and people without HIV (non- PWH) [3– 10]. In four of these studies, worse outcomes in PWH vs. non- PWH have been reported [3,7,9,10]. We assessed the frequency of COVID- 19 within a large prospective cohort of PWH in Spain during the first wave of the pandemic and compared the characteristics and clinical outcomes of hospitalized PWH with COVID- 19 with an age/ sexmatched control group of non- PWH. METHODS We performed a retrospective study of individuals with reverse transcription polymerase chain reaction (PCR)- confirmed COVID- 19 among PWH in active followup within the Spanish HIV Research Network Cohort (CoRIS) up to 30 June 2020. CoRIS is a prospective cohort of PWH aged > 13years, naïve to antiretroviral therapy (ART) at study entry, seen for the first time from 1 January 2004, in 46 participating centres from 13 of 17 regions in Spain. The CoRIS database collects demographic and clinical data, HIV transmission category, ART history, previous opportunistic diseases, specific non- AIDS diseases, and serological and immunovirological data. Internal quality controls are done annually [11]. PWH with confirmed COVID- 19 in CoRIS were identified by reviewing clinical records and laboratory registries. The data source for demographics, HIV- related characteristics and comorbidities in this study was the CoRIS database. COVID- 19- related clinical data were collected from the electronic medical records using an electronic case report form. Each hospitalized PWH with COVID- 19 was matched with five hospitalized non- PWH with COVID- 19 of the same age and sex randomly selected from COVID- 19@ Spain, a multicentre cohort of 4035 patients hospitalized with Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10922 patients in activefollow- up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non- PWH of the same age and sex randomly selected from COVID- 19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID- 19. The main outcome was allcause inhospital mortality. Results: Fortyfive PWH with PCR- confirmed COVID- 19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sexmatched controls were selected from the COVID- 19@Spain cohort. The median age in both groups was 53 (Q1– Q3, 46– 56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIVRNA <50 copies/mL, and the median (Q1– Q3) CD4 count was 595 (349– 798) cells/μL. No statistically significant differences were found between PWH and non- PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non- PWH, respectively (P=0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non- PWH (P=0.800). Conclusions: Our findings suggest that wellcontrolled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID- 19hospitalization. KEYWORDS Coronavirus, COVID- 19, HIV, SARS- CoV- 2 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 869 HIV MEDICINE TABLE 1 Demographics and comorbidity data of 45 people with HIV (PWH) with COVID- 19 stratified according to hospitalization Characteristic Nonhospitalized (N=24) Hospitalized (N=21) PTotal (N=45) Sex [n/N (%)] Male 20/24 (83.3) 19/21 (90.5) 0.482 39/45 (86.7) Female 4/24 (16.7) 2/21 (9.5) 6/45 (13.3) Age (years) Median (Q1– Q3) 38 (34– 48) 53 (46– 56) 0.001 46 (37– 56) Distribution [n/no. with data (%)] 0– 20years 0/23 (0) 0/21 (0) 0.007 0/44 (0) 21– 30years 5/23 (21.7) 0/21 (0) 5/44 (11.4) 31– 40years 9/23 (39.1) 1/21 (4.8) 10/44 (22.7) 41– 50years 4/23 (17.4) 8/21 (38.1) 12/44 (27.3) 51– 60years 4/23 (17.4) 8/21 (38.1) 12/44 (27.3) 61– 70years 1/23 (4.3) 3/21 (14.3) 4/44 (9.1) 71– 80years 0/23 (0) 1/21 (4.8) 1/44 (2.3) ≥81years 0/23 (0) 0/21 (0) 0 (0) Country of birth [n/no. with data (%)] Spain 18/24 (75.0) 12/21 (57.1) 0.205 30/45 (66.7) Other 6/24 (25.0) 9/21 (42.9) 15/45 (33.3) Transmission category [n/no. with data (%)] Homo/bisexual intercourse 16/24 (66.7) 7/21 (33.3) 0.051 23/45 (51.1) Heterosexual intercourse 7/24 (29.2) 8/21 (38.1) 15/45 (33.3) Injecting drug use 0/24 (0) 4/21 (19.1) 4/45 (8.9) Other/unknown 1/24 (4.2) 2/21 (9.5) 3/45 (6.7) Antiretroviral therapy [n/no. with data (%)] 24/24 (100.0) 20/21 (95.2) 0.280 44/45 (97.8) Last median CD4 count (Q1– Q3) (cells/μL) 434 (418– 870) 495 (349– 798) 0.958 481 (418– 823) HIVRNA <50 copies/mL [n/no. with data (%)] 16/17 (94.1) 17/18 (94.4) 0.967 33/35 (94.3) Comorbid conditions [n/no. with data (%)] Hypertension 2/24 (8.3) 9/21 (42.9) 0.007 11/45 (24.4) Coronary heart disease 0/24 (0) 2/21 (9.5) 0.122 2/45 (4.4) Prior heart failure 0/24 (0) 2/21 (9.5) 0.122 2/45 (4.4) Cerebrovascular disease 0/24 (0) 0/21 (0) — 0/45 (0) Diabetes 2/24 (8.3) 4/21 (19.0) 0.292 6/45 (13.3) Chronic lung disease (not asthma) 0/24 (0) 4/21 (19.0) 0.025 4/45 (8.9) Obesity (BMI ≥30kg/m2) 0/24 (0) 1/18 (5.6) 0.243 1/42 (2.4) Epilepsy 0/24 (0) 0/21 (0) — 0/45 (0) Other chronic neurological disorder 1/24 (4.2) 0/21 (0) 0.344 1/45 (2.2) Asthma 3/24 (12.5) 0/21 (0) 0.094 3/45 (6.7) Solid cancer (active) 0/24 (0) 1/21 (4.8) 0.280 1/45 (2.2) Haematological cancer (active) 0/24 (0) 0/21 (0) — 0/45 (0) Chronic kidney disease (GFR <60) 1/24 (4.2) 3/21 (14.3) 0.234 4/45 (8.9) Liver cirrhosis 0/24 (0) 0/21 (0) — 0/45 (0) Inflammatory disease 0/24 (0) 0/21 (0) — 0/45 (0) Dementia 0/23 (0) 0/21 (0) — 0/44 (0) (Continues) 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 870 | DÍEZ Et al. PCR- confirmed COVID- 19 in Spain [2]. The COVID- 19 SEIMC score (predictive of 30- day mortality), based on age, sex, dyspnoea, oxygen saturation, neutrophil- to- lymphocyte ratio and estimated glomerular filtration rate, was calculated retrospectively at admission in all patients [12]. The main outcome was allcause inhospital mortality. Descriptive analysis of individuals’ characteristics was carried out using frequency tables with percentages for categorical variables and median and quartiles for continuous variables. The study was approved by the Ethics Committee of Hospital General Universitario Gregorio Marañón. RESULTS Among 10922 PWH in activefollow- up within CoRIS during the study period, 45 (0.41%) had a recorded diagnosis of COVID- 19, 21 of whom (46.7%) were hospitalized. The demographics and clinical characteristics of the 45 PWH with COVID- 19 are shown in Table1, categorized according to whether they were hospitalized. In comparison with nonhospitalized PWH, those hospitalized were older (median age 38 vs. 53years, P=0.001) and more frequently diagnosed with arterial hypertension (8.3% vs. 42.9%, P=0.007) or chronic lung disease, not including asthma (0% vs. 19%, P=0.025). No statistically significant differences were found between both groups in the proportion of individuals on ART, CD4 cell counts or the proportion of those with HIVRNA load <50 copies/ mL. Among nonhospitalized PWH, 23 had a mild illness and one had moderate disease (pneumonia), whereas among hospitalized PWH, two had a mild illness, six had moderate disease, 12 had severe disease (severe pneumonia), and one had critical disease (acute respiratory distress syndrome). Two of the 45 PWH with COVID- 19, both hospitalized, died. The clinical characteristics and outcomes of the 21 hospitalized PWH with COVID- 19 and the 105 age/sexmatched non- PWH are shown in Table2. In both groups, the median [quartile 1 (Q1)– quartile 3 (Q3)] age was 53 (46– 56) years, and 90.5% were men. In PWH, 19.1% acquired HIV by injecting drug use, 95.2% were on ART, 94.4% had an HIVRNA <50 copies/mL, and the median (Q1– Q3) CD4 count was 495 (349– 798) cells/μL. A higher proportion of PWH than non- PWH were born abroad (42.9% vs. 20.4%, P = 0.028), particularly in Latin American countries. Likewise, a higher proportion of PWH than non- PWH had chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) formula of <60mL/min/1.73m2 for 3 months or more, irrespective of cause (14.3% vs. 2.9%, P=0.026). C- reactive protein (CRP) concentrations at baseline were statistically significantly lower in PWH than in non- PWH (median 13 vs. 49mg/L, respectively, P<0.001). No statistically significant differences were found between PWH and non- PWH in the number of comorbidities, presenting signs and symptoms, chest radiology findings, oxygen saturation at room air, other laboratory parameters and COVID- 19 SEIMC score on admission. During the hospital course, 61.9% of PWH and 78.4% of non- PHW received oxygen therapy, and 9.5% and 23.3%, respectively, underwent mechanical ventilation (P=0.158). No statistically significant differences were found between PWH and non- PWH in the percentage of patients receiving corticosteroids (33.3% vs. 27.4%, P=0.586), tocilizumab (4.8% vs. 16.7%, P=0.160) and remdesivir (0 vs. 2.9%, P=0.426). Death during admission was documented in two (9.5%) PWH and 12 (11.4%) non- PWH (P=0.800). Characteristic Nonhospitalized (N=24) Hospitalized (N=21) PTotal (N=45) Concomitant medication [n/no. with data (%)] ACE inhibitors 2/24 (8.3) 4/21 (19.0) 0.292 6/45 (13.3) ARBs 1/24 (4.2) 2/21 (9.5) 0.472 3/45 (6.7) Corticosteroids systemic 0/24 (0) 1/21 (4.8) 0.280 1/45 (2.2) Statins 3/24 (12.5) 5/21 (23.8) 0.322 8/45 (17.8) Summary of clinical syndromes Mild illness 23/24 (95.8) 2/21 (9.5) <0.001 25/45 (55.6) Moderate disease (pneumonia) 1/24 (4.2) 6/21 (28.6) 0.024 7/45 (15.6) Severe disease (severe pneumonia) 0/24 (0) 12/21 (57.1) <0.001 12/45 (26.7) Critical disease (ARDS) 0/24 (0) 1/21 (4.8) 0.280 1/45 (2.2) Death 0/24 (0) 2/21 (9.5) 0.122 2/45 (4.4) Abbreviations: ACE, angiotensinconverting enzyme; ARBs, angiotensin receptor blockers; ARDS, acute respiratory distress syndrome; BMI, body mass index; GFR, glomerular filtration rate; PWH, people with HIV; Q1/Q3, first/third quartile. TABLE 1 (Continued) 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 871 HIV MEDICINE TABLE 2 Clinical characteristics, treatment and outcome of hospitalized patients with COVID- 19 PWH (N=21) Non- PWH (N=105) P Sociodemographic characteristics Male sex [n/N (%)] 19/21 (90.5) 95/105 (90.5) 1.00 Age (no. with data) 21 105 Median (Q1– Q3) (years) 53 (46– 56) 53 (46– 56) 1.00 Country of birth [n/no. with data (%)] Spain 12/21 (57.1) 82/103 (79.6) 0.028 Other 9/21 (42.9) 21/103 (20.4) Number of comorbidities [n/no. with data (%)] None 8/18 (44.4) 36/91 (39.6) 0.798 1– 2 7/18 (38.9) 43/91 (47.3) ≥3 3/18 (16.7) 12/91 (13.2) Types of comorbidity [n/no. with data (%)] Hypertension 9/21 (42.9) 37/103 (35.9) 0.549 Chronic heart disease 3/21 (14.3) 6/104 (5.8) 0.168 Diabetes 4/21 (19.0) 17/104 (16.3) 0.763 Chronic lung disease (not asthma) 4/21 (19.0) 13/105 (12.4) 0.414 Obesity (BMI ≥30 kg/m2) 1/18 (5.6) 19/94 (20.2) 0.137 Other chronic neurological disorder 0/21 (0) 5/104 (4.8) 0.305 Asthma 0/21 (0) 6/105 (5.7) 0.262 Solid cancer (active) 1/21 (4.8) 2/105 (1.9) 0.433 Haematological cancer (active) 0/21 (0) 2/104 (1.9) 0.522 Chronic kidney diseasea 3/21 (14.3) 3/104 (2.9) 0.026 Liver cirrhosis 0/21 (0) 3/104 (2.9) 0.431 Inflammatory disease 0/21 (0) 4/105 (3.8) 0.363 Dementia 0/21 (0) 3/105 (2.9) 0.433 Signs and symptoms (>10%) [n/no. with data (%)] History of fever 19/21 (90.5) 94/105 (89.5) 0.896 Cough 14/21 (66.7) 80/105 (76.2) 0.360 Malaise 12/21 (57.1) 71/102 (69.6) 0.267 Dyspnoea 14/21 (66.7) 59/103 (57.3) 0.426 Upper respiratory tract symptoms 9/21 (42.9) 30/103 (29.1) 0.217 Myalgia/arthralgia 4/21 (19.0) 27/97 (27.8) 0.407 Diarrhoea 4/21 (19.0) 16/103 (15.5) 0.690 Headache 4/21 (19.0) 13/98 (13.3) 0.492 Vomiting/nausea 3/21 (14.3) 16/99 (16.2) 0.831 Chest pain 2/21 (9.5) 13/98 (13.3) 0.639 Chest radiography [n/no. with data (%)] Infiltrates present at baseline 18/20 (90.0) 86/100 (86.0) 0.631 Bilateral opacities 15/18 (83.3) 62/82 (75.6) 0.481 Capillary O2 saturation at room air (%) No. with data 19 89 Median (Q1– Q3) 95 (89– 97) 95 (92– 97) 0.647 Laboratory parameters Leukocyte count (n with data) 17 103 Median (Q1– Q3) (cells/µL) 6540 (5590– 8120) 6400 (4580– 7900) 0.489 (Continues) 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 872 | DÍEZ Et al. DISCUSSION In this retrospective study nested in a large prospective cohort of PWH in Spain, COVID- 19 was reported as confirmed in 0.4% of individuals up to 30 June 2020, 46.7% of whom were hospitalized. Most individuals had wellcontrolled HIV infection; however, those hospitalized were older and more frequently afflicted with underlying comorbidities than those managed ambulatorily. These findings are similar to those reported in two other sizeable multicentre retrospective studies with PWH in Spain and Italy, where 0.4% and 0.3% of PWH developed COVID- 19, and 63.9% and 55.1%, respectively, were hospitalized [13,14]. A higher frequency of COVID- 19 was found in a populationbased study in the West Cape region in South Africa, in which the infection was confirmed in 7.4% of PWH [3]. We also compared the characteristics and outcomes of hospitalized PWH with COVID- 19 with age/sexmatched non- PWH controls from a cohort of hospitalized individuals with COVID- 19 in Spain [2]. Clinical features and severity score on admission were well matched between the groups. However, serum CRP concentrations indicative of systemic inflammation were lower in PWH than in non- PWH. Notwithstanding this, median serum concentrations of CRP in both groups were PWH (N=21) Non- PWH (N=105) P Lymphocyte count (n with data) 17 102 Median (Q1– Q3) (cells/µL) 1170 (930– 1500) 1100 (820– 1450) 0.247 Neutrophil count (n with data) 17 104 Median (Q1– Q3) (cells/μL) 4370 (3780– 6730) 4310 (2900– 6050) 0.497 Neutrophil- to- lymphocyte ratio [n with data (%)] 17 102 Median (Q1– Q3) 3.6 (2.2– 5.9) 3.7 (2.4– 6.6) 0.838 D- Dimer [n with data] 13 45 Median (Q1– Q3) (ng/mL) 591 (349– 1324) 490 (310– 880) 0.508 ALT (n with data) 16 93 Median (Q1– Q3) (U/L) 29 (12– 46) 39 (22– 58) 0.234 Creatinine (n with data) 17 104 Median (Q1– Q3) (mg/dL) 0.9 (0.8– 1.0) 0.9 (0.8– 1.1) 0.932 C- reactive protein (n with data) 17 98 Median (Q1– Q3) (mg/L) 13 (9– 17) 49 (21– 116) <0.001 COVID- 19 SEIMC score No. with data 15 85 Median (Q1– Q3) 4 (2– 7) 5 (3– 7) 0.996 Supportive therapy [n/no. with data (%)] Oxygen therapy (nasal, reservoir, mask) 13/21 (61.9) 88/102 (78.4) 0.108 BiPAP, CPAP, HFNO 0/21 (0) 20/102 (19.6) 0.027 Mechanical ventilation 2/21 (9.5) 24/103 (23.3) 0.158 Inotropes/vasopressors 2/21 (9.5) 17/102 (16.7) 0.409 Renal replacement therapy/dialysis 1/21 (4.8) 3/100 (3.0) 0.681 Treatment [n/no. with data (%)] Remdesivir 0/21 3/102 (2.9) 0.426 Corticosteroids 7/21 (33.3) 28/102 (27.4) 0.586 Tocilizumab 1/21 (4.8) 17/102 (16.7) 0.160 Outcomes [n/no. with data (%)] Death 2/21 (9.5) 12/105 (11.4) 0.800 Abbreviations: ALT, alanine, aminotransferase; BiPAP, bilevel positive airway pressure; BMI, body mass index; CPAP, continuous positive airways pressure; HFNO, highflow nasal oxygen therapy; non- PWH, people not infected with HIV; PWH, people with HIV; Q1/Q3, first/third quartile; SEIMC, Spanish Society of Infectious Diseases and Clinical Microbiology. aDefined as an estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) formula of <60mL/min/1.73m2 for 3 months or more, irrespective of cause. TABLE 2 (Continued) 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 873 HIV MEDICINE below the cutoff values associated with severe disease and fatal outcomes (50 and 75mg/L, respectively) [15]. It is notable that a higher proportion of PWH than non- PWH were born abroad, particularly in Latin American countries, most likely because these individuals are overrepresented in CoRIS compared with Spain's general population. Other explanations include increased exposure to SARS- CoV- 2 due to differences in societal factors or differences in the genetic background that could influence COVID- 19 acquisition. In a singlecentre case series from the UK, hospitalized PWH with COVID- 19 were more likely to be of black ethnicity [4]. However, no differences in race/ethnicity between hospitalized PWH and non- PWH were found in two multicentre case series from the USA [5,6]. We found that mortality for COVID- 19 among PWH was 4.4% overall and 9.5% among those hospitalized, a figure not significantly different from the 11.4% seen in the age/ sexmatched non- PWH controls. Of note, approximately a third of hospitalized patients with COVID- 19 received corticosteroids, and a smaller proportion received tocilizumab or remdesivir, with no statistically significant differences found between PWH and non- PWH. No significant differences in mortality between PWH and non- PWH have been described in four studies from the UK and the USA [4- 6,8], including a large retrospective study of the US Veterans Aging Cohort Study that included all veterans with HIV and 1:2 age- , race/ethnicity- , sex- and sitematched uninfected veterans, in which no evidence was found of increased risk of severe COVID- 19 outcomes including death by HIV status [8]. Nevertheless, an association between HIV infection and COVID- 19 death has been found in South Africa [3] and two extensive studies from the UK [7,9], although one or more confounding factors (socioeconomic status and type of occupation, comorbidities, body mass index, smoking and markers of HIV control) could not be ruled out in these studies. In a recent cohort study of linked HIV diagnosis, COVID- 19 laboratory diagnosis and hospitalization databases in New York State, PWH were more likely to receive a diagnosis of, be hospitalized with, and die inhospital with COVID- 19 compared with non- PWH [10]. In this study, COVID- 19hospitalization and mortality remained significantly elevated for PWH after demographic adjustment; but again, the role played by comorbidities, risk behaviours and socioeconomic status could not be determined. Our study is limited by retrospective design and by the small number of PWH with COVID- 19. Our work is also limited by the absence of critical socioeconomic information about housing, employment and level of education. Strengths include having been carried out in a prospective cohort of PWH, a comparison with age- and sexmatched non- PWH controls, and the use of a validated predictive scoring system. In conclusion, our findings suggest that wellcontrolled HIV infection does not modify the clinical presentation or worsen clinical outcomes in patients hospitalized with COVID- 19. ACKNOWLEDGMENTS We acknowledge all members of the Spanish HIV Research Network Cohort (CoRIS) who made this research possible (see Appendix). CONFLICT OF INTEREST JCL reports honoraria for advice or public speaking from Gilead, MSD, Janssen and ViiV Healthcare. JRB reports honoraria for advice or public speaking from Abbvie, Gilead, MSD, Janssen and ViiV Healthcare, and grants from Gilead. LJG- F reports honoraria for advice or public speaking from MSD and grants from GILEAD. FG reports honoraria for advice or public speaking from Janssen and ViiV Healthcare. IS- G reports honoraria for advice or public speaking from Gilead, MSD and ViiV Healthcare. JRA reports honoraria for advice or public speaking from Alexa, Gilead, MSD, Janssen, Serono, Teva and ViiV Healthcare, and grants from Alexa, Gilead, Janssen, MSD, Serono, Teva and ViiV Healthcare. SM reports honoraria for advice or public speaking from Gilead, MSD, Janssen and ViiV Healthcare, and grants from Gilead, MSD and ViiV Healthcare. JG- G reports honoraria for advice or public speaking from Gilead, MSD, Janssen and ViiV Healthcare. IJ reports honoraria for advice or public speaking from Gilead and ViiV Healthcare, and grants from MSD. JB reports honoraria for advice or public speaking from Abbvie, Gilead, MSD, Janssen and ViiV Healthcare, and grants from Abbvie, Gilead, MSD and ViiV Healthcare. CD, JDR- R, RM, SC, GS, JP, LJG- F, JLG- S, CA and MN have nothing to disclose. This work was supported by the Instituto de Salud Carlos III (ISCII) (grant no. COV20/00108) and the Spanish AIDS Research Network (RD16/0025), which is included in the Spanish I+D+I Plan and is cofunded by ISCIII- Subdirección General de Evaluación and European Funding for Regional Development (FEDER). AUTHOR CONTRIBUTIONS JB conceived the study. CD, JRA, SM, JG and IJ made substantial contributions to the conception and design. JDR and IJ analysed the data. RM, JCL, JRB, SC, GS, JP, LJG- F, FG, JLG, IS, CA and MN made substantial contributions to the acquisition of data. JB drafted the manuscript, and all authors revised it critically and approved the final version. ORCID José R. Blanco https://orcid.org/0000-0002-4268-0150 Gloria Samperiz https://orcid.org/0000-0003-0693-2266 Inés Suárez- García https://orcid.org/0000-0002-7016-716X Juan Berenguer https://orcid.org/0000-0001-8541-8200 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. 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HIV Med. 2021;22:867– 876. https://doi. org/10.1111/hiv.13145 APPENDIX Members of the the Spanish HIV Research Network Cohort (CoRIS) Executive committee: Santiago Moreno, Inma Jarrín, David Dalmau, Maria Luisa Navarro, Maria Isabel González, Federico Garcia, Eva Poveda, Jose Antonio Iribarren, Félix Gutiérrez, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, M Ángeles Muñoz- Fernández. Fieldwork data management and analysis:Inmaculada Jarrin, Belén Alejos, Cristina Moreno, Carlos Iniesta, Marta Rava, Rebeca Izquierdo. BioBanK HIV Hospital General Universitario Gregorio Marañón: M Ángeles Muñoz- Fernández, Irene Consuegra Fernández. Hospital General Universitario de Alicante (Alicante): Esperanza Merino, Gema García, Irene Portilla, Iván Agea, Joaquín Portilla, José Sánchez- Payá., Juan Carlos Rodríguez, Lina Gimeno, Livia Giner, Marcos Díez, Melissa Carreres, Sergio Reus, Vicente Boix, Diego Torrús. Hospital Universitario de Canarias (San Cristóbal de la Laguna): Ana López Lirola, Dácil García, Felicitas Díaz- Flores, Juan Luis Gómez, María del Mar Alonso, Ricardo Pelazas., Jehovana Hernández, María Remedios Alemán, María Inmaculada Hernández. Hospital Universitario Central de Asturias (Oviedo): Víctor Asensi, Eulalia Valle, María Eugenia Rivas Carmenado, Tomás Suárez- Zarracina Secades, Laura Pérez Is. Hospital Universitario 12 de Octubre (Madrid): Rafael Rubio, Federico Pulido, Otilia Bisbal, Asunción Hernando, Lourdes Domínguez, David Rial Crestelo, Laura Bermejo, Mireia Santacreu. Servicio de Enfermedades Infecciosas. Hospital Universitario Donostia. Instituto de Investigación BioDonostia. (Donostia- San Sebastián): José Antonio Iribarren, Julio Arrizabalaga, María José Aramburu, Xabier Camino, Francisco Rodríguez- Arrondo, Miguel Ángel von Wichmann, Lidia Pascual Tomé, Miguel Ángel Goenaga, Mª Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Aitziber Lizardi, Xabier Kortajarena, Mª Pilar Carmona Oyaga, Maitane Umerez Igartua. Hospital General Universitario De Elche (Elche): Félix Gutiérrez, Mar Masiá, Sergio Padilla, Catalina Robledano, Joan Gregori Colomé, Araceli Adsuar, Rafael Pascual, Marta Fernández, José Alberto García, Xavier Barber, Vanessa Agullo Re, Javier Garcia Abellán, Reyes Pascual Pérez, María Roca. Hospital Universitari Germans Trias i Pujol (Can Ruti) (Badalona): Roberto Muga, Arantza 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 875 HIV MEDICINE Sanvisens, Daniel Fuster. Hospital General Universitario Gregorio Marañón (Madrid): Juan Berenguer, Juan Carlos López, Isabel Gutiérrez, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz- Echevarría, Francisco Tejerina, Francisco José Parras, Pascual Balsalobre, Cristina Diez, Leire Pérez Latorre, Chiara Fanciulli. Hospital Universitari de Tarragona Joan XXIII (Tarragona): Francesc Vidal, Joaquín Peraire, Consuelo Viladés, Sergio Veloso, Montserrat Vargas, Montserrat Olona, Anna Rull, Verónica Alba, Elena Yeregui, Jenifer Masip, Laia Reverté. Hospital Universitario y Politécnico de La Fe (Valencia): Marta Montero, José López Aldeguer, Marino Blanes, María Tasias Pitarch, Iván Castro Hernández, Eva Calabuig, Sandra Cuéllar, Miguel Salavert Lletí, Juan Fernández Navarro. Hospital Universitario La Paz/IdiPAZ: Juan González- Garcia, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino de la Serna, Carmen Busca, Joanna Cano, Julen Cardiñanos, Juan Miguel Castro, Ana Delgado Hierro, Luis Escosa, Pedro Herranz, Víctor Hontañón, Silvia García- Bujalance, Milagros García López- Hortelano, Alicia González- Baeza, Rosa de Miguel, Maria Luz Martín- Carbonero, Mario Mayoral, Maria Jose Mellado, Rafael Micán, Rocio Montejano, María Luisa Montes, Victoria Moreno, Ignacio Pérez- Valero, Guadalupe Rúa Cebrián, Berta Rodés, Talia Sainz, Elena Sendagorta, Eulalia Valencia. Hospital San Pedro Centro de Investigación Biomédica de La Rioja (CIBIR) (Logroño): José Ramón Blanco, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Laura Pérez- Martínez. Hospital Universitario Miguel Servet (Zaragoza): Piedad Arazo, Gloria Sampériz. Hospital Universitari MutuaTerrassa (Terrasa): David Dalmau, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez- Lacasa, Pablo Velli, Roser Font, Marina Martinez, Francesco Aiello. Complejo Hospitalario de Navarra (Pamplona): Maria Rivero Marcotegui, Jesús Repáraz, María Gracia Ruiz de Alda, María Teresa de León Cano, Beatriz Pierola. Corporació Sanitària Parc Taulí (Sabadell): María José Amengual, Gemma Navarro, Manel Cervantes, Sonia Calzado, Marta Navarro Vilasaro. Hospital Universitario de La Princesa (Madrid): Ignacio de los Santos, Jesús Sanz Sanz, Ana Salas, Cristina Sarria, Lucio J. Garcia- Fraile Fraile, Enrique Martín Gayo. Hospital Universitario Ramón y Cajal (Madrid): Santiago Moreno, José Luis Casado, Fernando Dronda, Ana Moreno, Maria Jesús Pérez Elías, Carolina Gutiérrez, Nadia Madrid, Santos del Campo, Sergio Serrano, Maria Jesús Vivancos, Javier Martínez Sanz, Usua Anxa Urroz, Tamara Velasco, Alejandro Vallejo. Hospital General Universitario Reina Sofía (Murcia): Enrique Bernal, Alfredo Cano Sanchez, Antonia Alcaraz, Joaquín Bravo Urbieta, Ángeles Muñoz Perez, Maria Jose Alcaraz, Maria del Carmen Villalba. Hospital Nuevo San Cecilio (Granada): Federico García, José Hernández Quero, Leopoldo Muñoz Medina, Marta Alvarez, Natalia Chueca, David Vinuesa, Clara Martinez- Montes, Carlos Guerrero, Adolfo de Salazar Gonzalez, Ana Fuentes. Centro Sanitario Sandoval (Madrid): Jorge Del Romero, Montserrat Raposo Utrilla, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi. Hospital Clínico Universitario de Santiago (Santiago de Compostela): Antonio Antela, Elena Losada. Hospital Universitario Son Espases (Palma de Mallorca): Melchor Riera, María Peñaranda, Mª Angels Ribas, Antoni A Campins, Carmen Vidal, Francisco Fanjul, Javier Murillas, Francisco Homar, Helem H Vilchez, Maria Luisa Martin, Antoni Payeras. Hospital Universitario Virgen de la Victoria (Málaga): Jesús Santos, Cristina Gómez Ayerbe, Isabel Viciana, Rosario Palacios, Carmen Pérez López, Carmen Maria Gonzalez- Domenec. Hospital Universitario Virgen del Rocío (Sevilla): Pompeyo Viciana, Nuria Espinosa, Luis Fernando López- Cortés. Hospital Universitario de Bellvitge (Hospitalet de Llobregat): Daniel Podzamczer, Arkaitz Imaz, Juan Tiraboschi, Ana Silva, María Saumoy, Paula Prieto. Hospital Universitario Valle de Hebrón (Barcelona): Esteban Ribera, Adrian Curran. Hospital Costa del Sol (Marbella): Julián Olalla, Javier Pérez Stachowski, Alfonso del Arco, Javier de la Torre, José Luis Prada, José María García de Lomas. Hospital General Universitario Santa Lucía (Cartagena): Onofre Juan Martínez, Francisco J. Vera, Lorena Martínez, Josefina García, Begoña Alcaraz, Amaya Jimeno. Complejo Hospitalario Universitario a Coruña (Chuac) (A Coruña) Ángeles Castro, Berta Pernas, Álvaro Mena. Hospital Universitario Basurto (Bilbao): Josefa Muñoz, Miren Zuriñe Zubero, Josu Mirena Baraia- Etxaburu, Sofía Ibarra, Oscar Luis Ferrero, Josefina López de Munain, Mª Mar Cámara, Mireia de la Peña, Miriam Lopez, Iñigo Lopez Azkarreta. Hospital Universitario Virgen de la Arrixaca (El Palmar): Carlos Galera, Helena Albendin, Aurora Pérez, Asunción Iborra, Antonio Moreno, Maria Angustias Merlos, Asunción Vidal, Marisa Meca. Hospital de la Marina Baixa (La Vila Joiosa): Concha Amador, Francisco Pasquau, Javier Ena, Concha Benito, Vicenta Fenoll, Concepción Gil Anguita, José Tomás Algado. Hospital Universitario Infanta Sofía (San Sebastián de los Reyes): Inés Suárez- García, Eduardo Malmierca, Patricia González- Ruano, Dolores Martín Rodrigo, Mª Pilar Ruiz Seco. Hospital Universitario de Jaén (Jaén): Mohamed Omar, María Amparo Gómez Vidal. Hospital San Agustín (Avilés): Miguel Alberto de Zarraga. Hospital Clínico San Carlos (Madrid): Vicente Estrada, Maria Jesús Téllez, Jorge Vergas, Juncal Pérez- Somarriba. Hospital Universitario Fundación Jiménez Díaz (Madrid): Miguel Górgolas, Alfonso Cabello, Beatriz Álvarez, Laura Prieto. Hospital Universitario Príncipe de Asturias (Alcalá de Henares): José Sanz Moreno, Alberto Arranz, Cristina Hernández Gutiérrez, María Novella Mena. Hospital 14681293, 2021, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/hiv.13145 by Universidad De Sevilla, Wiley Online Library on [01/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License