key: cord-0996448-43ao5x2w authors: Nasreddine, Rakan; Florence, Eric; Moutschen, Michel; Yombi, Jean‐Cyr; Goffard, Jean‐Christophe; Derdelinckx, Inge; Lacor, Patrick; Vandekerckhove, Linos; Messiaen, Peter; Vandecasteele, Stefaan; Delforge, Marc; De Wit, Stéphane title: Clinical characteristics and outcomes of COVID‐19 in people living with HIV in Belgium: A multicenter, retrospective cohort date: 2021-02-09 journal: J Med Virol DOI: 10.1002/jmv.26828 sha: d595a98248bfa27bde02494d086b0b49bf69128e doc_id: 996448 cord_uid: 43ao5x2w The aim of this study was to describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID‐19) among people living with HIV (PLWH) in Belgium. We performed a retrospective multicenter cohort analysis of PLWH with either laboratory‐confirmed, radiologically diagnosed, or clinically suspected COVID‐19 between February 15, 2020 and May 31, 2020. The primary endpoint was outcome of COVID‐19. Secondary endpoints included rate of hospitalization and length of hospital stay and rate of Intensive Care Unit (ICU) admission and mechanical ventilation. One hundred and one patients were included in this study. Patients were categorized as having either laboratory‐confirmed (n = 65), radiologically‐diagnosed (n = 3), or clinically suspected COVID‐19 (n = 33). The median age was 51.3 years (interquartile range [IQR] 41.3–57.3) and 44% were female. Ninety‐four percent of patients were virologically suppressed and 67% had a CD4(+) cell count more than or equal to 500 cells/µl. Overall, 46% of patients required hospitalization and the median length of hospital stay was 6 days (IQR 3–15). Age more than or equal to 50 years, Black Sub‐Saharan African patients, and being on an integrase strand transfer inhibitor‐based regimen were associated with being hospitalized. ICU admission and mechanical ventilation was required for 15% and 10% of all patients respectively. Overall, 9% of patients died while 78 (77%) patients made a full recovery. HIV patients with COVID‐19 experienced a high degree of hospitalization despite having elevated CD4(+) cell counts and a high rate of virologic suppression. Matched case‐control studies are warranted to measure the impact that HIV may have on patients with COVID‐19. In December 2019, an outbreak of coronavirus disease 2019 caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China. As the number of cases continued to increase at an alarming rate worldwide, the World Health Organization declared COVID-19 a pandemic on March 11, 2020. 1 With an estimated 37.9 million people living with HIV (PLWH) worldwide, 2 it would be expected that a significant number of these patients will experience COVID-19. Characteristics such as older age, hypertension, and diabetes mellitus have been identified as risk factors for more severe infection and worse prognosis, 3, 4 however there is limited evidence regarding the impact of HIV infection on the severity and mortality related to COVID-19. The presumption is that HIV would have a deleterious effect due to immune deficiency, however, this may also be paradoxically protective. As of June 26, 2020, the time of analysis for this study, Belgium had been one of the more affected countries with 61,106 confirmed COVID-19 cases and 9726 deaths. 5 We describe here the clinical characteristics and outcomes of COVID-19 among PLWH in Belgium. This is a retrospective, observational, multicenter cohort study. Data were anonymously extracted, using a standardized data collection form, from the electronic health records of 10 HIV reference centers (HRCs) in Belgium, which work in concert as members of the Belgian Research on AIDS and HIV Consortium (BREACH). This study was done in accordance with local legislation and informed consent was waived. The inclusion criteria were as follows: male or female patients aged 18 years or above with confirmed HIV-1 infection having one of the following COVID-19 case definitions, defined according to Belgian national guidelines, 6 date of COVID-19 diagnosis, current combined antiretroviral therapy (cART) regimen being taken, and the rate of and reasons for HIV treatment interruption or modification during the COVID-19 episode; and (c) COVID-19-related characteristics such as a description of the symptoms experienced, chest CT scan and SARS-CoV-2 test results, hospitalization and Intensive Care Unit (ICU) admission, and types of treatment(s) received for COVID-19. The primary endpoint was to evaluate the outcome of COVID-19 in PLWH categorized as either fully recovered, recovery ongoing, or death. Secondary endpoints included the rate of hospitalization and length of hospital stay and the rate of ICU admission and mechanical ventilation. Descriptive statistics on demographics were used to describe the overall study population in addition to three subsets of patients; laboratory-confirmed, radiologically diagnosed, and clinically sus- Of the roughly 16,000 HIV patients that are regularly followed in the diagnosis, 97% of the study cohort was treatment-experienced, 94% had an HIV-1 VL less than 50 copies/ml, and 67% had a CD4 + cell count more than or equal to 500 cells/µl. The most commonly pre- COVID-19-related characteristics and outcomes are presented in Table 3 . Fever (59%), cough (58%), and fatigue (58%) were the most common presenting symptoms among all patients. Anosmia/ageusia occurred in 32% of patients. Chest CT scan was performed in 35% of patients overall and bilateral infiltrates were present in 28/35 (80%) patients (two patients had a normal CT scan). Overall, 68 (67%) patients underwent SARS-CoV-2 testing and nasopharyngeal swab was the most common type of sample used (63/68; 93%). Of the 65 patients that had laboratory-confirmed COVID-19, 57 (88%) had a positive SARS-CoV-2 PCR on nasopharyngeal swab, 3 (5%) had a positive SARS-CoV-2 Ag on nasopharyngeal swab, and 3 (5%) had a positive SARS-CoV-2 PCR on bronchoalveolar lavage. In addition to supportive care, 36/101 patients received at least one type of off-label treatment for COVID-19 with 35/ 36 (97.2%) patients receiving hydroxychloroquine. The hospitalization rates for laboratory-confirmed, radiologically diagnosed, and clinically suspected patients with COVID-19 was 63%, 100%, and 6%, respectively. The overall median length of hospital stay was 6 days (IQR 3-15). Multivariable logistic regression analysis revealed that age more than or equal to 50 years (odds ratio [ (14) No 47 (72) 3 (100) 16 (49) 66 (65) Ex-smoker 9 (14) 0 (0) 8 (24) 17 (17) Data not available 4 (6) 0 (0) 0 (0) 4 (4) Co-morbidities, n (%) Syndrome (MERS) patients, HIV was not reported to be a risk factor. 8, 9 In contrast, PLWH were observed to have more severe influenza virus infections with an increased risk of hospitalization and death as a result. 10, 11 The aim of this study was to address some of the unknowns related to COVID-19 in PLWH. We included three categories of COVID-19 patients; laboratoryconfirmed, radiologically diagnosed, and clinically suspected because first, these were the COVID-19 case definitions used in Belgium, 6 second, the influenza season was concluding in Belgium by the time the inclusion period for this study began, 12 The overall hospitalization rate for our cohort was 46%. The hospitalization rate for PLWH described in the literature ranges between 27.7% and 42.4%. 14, 15 The ICU admission rate and the rate of mechanical ventilation in our cohort was 15% and 10%, respectively. Various studies have reported an ICU admission rate ranging between 7.1% and 18.2% [15] [16] [17] and a rate of mechanical ventilation ranging between 4.3% and 55.6%. [14] [15] [16] [17] [18] [19] In terms of recovery, 77% of patients in our cohort experienced a full recovery while 9% died. Mortality rates among PLWH coinfected with SARS-CoV-2 have been reported to be as low as 4% increasing up to 78%. 14, [16] [17] [18] [19] [20] African patients and those above the age of 50 had a significantly higher risk of being hospitalized, findings which have been previously reported. 19, 20 In contrast to previous reports, however, being an active smoker and having hypertension or diabetes mellitus were not found to be significant risk factors for hospitalization. 3, 4 Potential factors that may explain the discrepancy between our findings and those of other studies include differences in age and overall prevalence of comorbidities as well as the small sample size of our cohort. There is a debate whether antiretrovirals play a role in preventing or treating with higher CD4 + cell counts and on suppressive cART. 16, 17, 19, 20, 24 In our cohort, 94% of laboratory-confirmed COVID-19 patients had an HIV-1 VL less than 50 copies/ml and 67% had a CD4 + cell count of more than or equal to 500 cells/µl. A possible explanation for such an increased rate of complication in PLWH may be the fact that the host response to SARS-CoV-2 requires lymphocytes and HIV-related lymphopenia may promote the progression of disease. 19 However, perhaps this striking difference in hospitalization rates between our cohort and the general population can be explained by a form of "hospitalization bias" whereby physicians may perceive PLWH as more fragile or at risk of complication and choose to admit these patients out of an abundance of caution resulting in a higher rate of hospitalization. Data concerning the onset and duration of symptoms along with the vital signs, laboratory results, and socioeconomic status of patients upon admission to the hospital was incomplete, preventing us from providing further insight on this matter. Moreover, the case fatality rate among laboratory-confirmed COVID-19 patients in our cohort was 14% (9/65 patients), which was slightly lower than the general population in Belgium (16%), where 9726 patients out of 61,106 confirmed COVID-19 cases died. 5 Indeed, there have been reports that PLWH coinfected with SARS-CoV-2 are not at greater risk of experiencing complications. 14, 15, 18, 25 The hypothesis put forth explaining this is that there is a paradoxical prevention from the cytokine storm seen in COVID-19 due to a combination of the absence of T cell activation and HIV-related lymphopenia. 26 Our study has some limitations. The small sample size prevents us from generalizing our results. Comparison with patients without HIV was not done for this study. Lastly, it is to be noted that the number of laboratory-confirmed cases in our cohort, as in the general population in Belgium, is probably underestimated given that early in the pandemic national recommendations placed restrictions on confirmatory testing of cases. In conclusion, the results of this analysis suggest that HIV patients with COVID-19 are at a greater risk of hospitalization, when compared to the general population, but have a similar mortality rate. Matched case-control studies are warranted therefore to precisely measure the impact of HIV on the clinical course of COVID-19. Furthermore, PLWH should be included in future investigational trials that will evaluate the potential of treatments against COVID-19. World Health OrganizationWHO Director-General's Opening Remarks at the Media Briefing on COVID-19. Geneva: WHO; 2020. https:// www.who.int/dg/speeches/detail/who-director-general-s-openingremarks-at-the-media-briefingon-covid Clinical characteristics of coronavirus disease 2019 in China Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy COVID-19-Bulletin Epidémiologique Brussels, Sciensano Définition de Cas, Indications de Demande d'un Test et Déclaration Obligatoire de Cas COVID-19 Brussels United Nations Statistics Division. Composition of Macro Geographical (Continental) Regions, Geographical Sub-Regions, and Selected Economic Other Groupings Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study Clinical course and outcomes of critically ill patients with middle east respiratory syndrome coronavirus infection Potential impact of COVID-19 in people living with HIV: experience from previous 21st century coronaviruses epidemics Severe influenza-associated respiratory infection in high HIV prevalence setting, South Africa Influenza-Bulletin Epidémiologique Brussels, Sciensano Epidémiologie du Sida et de l'Infection à VIH en Belgique: situation au 31 Décembre Clinical features and outcomes of HIV patients with coronavirus disease COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients Patterns of HIV and SARS-CoV-2 coinfection in Wuhan Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort Clinical characteristics and outcomes in people living with HIV hospitalized for COVID-19 Clinical features and outcome of HIV/ SARS-CoV-2 coinfected patients in the Hospitalized patients with COVID-19 and HIV: a case series Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study Incidence and severity of COVID-19 in HIV-positive persons receiving antiretroviral therapy: a cohort study Clinical outcomes and immunologic characteristics of Covid-19 in people with HIV COVID-19 in patients with HIV: clinical case series infection alter the clinical course of SARS-CoV-2 infection? when less is better How to cite this article: Nasreddine R Clinical characteristics and outcomes of COVID-19 in people living with HIV in Belgium: A multicenter, retrospective cohort The authors declare that there are no conflict of interests. All authors contributed to the study concept and design. Data analysis was performed by Rakan Nasreddine and Marc Delforge. Rakan Nasreddine drafted the manuscript. All authors reviewed and approved the final version. The peer review history for this article is available at https://publons. com/publon/10.1002/jmv.26828 The data that support the findings of this study are available from the corresponding author upon reasonable request. http://orcid.org/0000-0002-1265-1500