key: cord-0823291-0k5cidxw
authors: Cabello, Alfonso; Zamarro, Belén; Nistal, Sara; Victor, Virginia; Hernández, Jana; Prieto-Pérez, Laura; Carrillo, Irene; Álvarez, Beatriz; Fernández-Roblas, Ricardo; Hernández-Segurado, Marta; Becares, Javier; Benito, José Miguel; Rallón, Norma; Téllez, Raquel; Castaño, Ángel Luis; Herrero, Antonio; Górgolas, Miguel
title: COVID-19 DISEASE IN PEOPLE LIVING WITH HIV: A MULTICENTER CASE-SERIES STUDY
date: 2020-10-27
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.10.060
sha: b1ec5fba6cf907ee3517842545576dd103116392
doc_id: 823291
cord_uid: 0k5cidxw

OBJECTIVES: The information of how COVID-19 infection affects people living with HIV (PLHIV) is still scarce. METHODS: Observational study was conducted in four of public hospitals in Madrid. All HIV patients with confirmed or suspected COVID-19 disease were included and compared with COVID-19 infected patients without HIV infection. RESULTS: Sixty-three patients with HIV infection were analysed. The median age was 46 years (IQR: 37-56 years), 88.9% were men. The median time of HIV infection was 10.8 years (IQR: 6.5 - 16.8 years), 96.8% were on antiretroviral therapy. 84.1% had previous comorbidities. The most common symptoms were fever(66.1%), cough(66.1%) and dyspnea(46.8%). Pneumonia was found in 47.5%, 28.6% of patients had severe disease and 32.3% was admitted to hospital. The ICU admission rate and the mortality rate were both 3.17%. Significant association was observed between age, arterial hypertension, overweight, diabetes mellitus and the severity of COVID-19 disease. No association was observed between HIV-related factors. The rate of COVID-19 disease in HIV-patients was 1,68%. A similar hospitalization (31.74% vs 32.57%) and ICU admission rate (3.17% vs 2%) was observed with non-HIV infected patients. A lower mortality rate during hospitalization (10% vs 21.37%) and global mortality rate (3.17% vs 6.96%) were observed. CONCLUSIONS: Established poor prognostic factors, such as age and comorbidities, represent also the main determinants for PLHIV. Neither the HIV severity, nor the type of ARV treatment seem to influence the outcome of COVID-19 infection. Large prospective cohorts are needed in order to establish the differences between HIV positive and negative patients.

On July 1 st , the SARS-CoV-2 pandemic has affected around 10 million people, causing over 510,000 deaths 1 . On the other hand, more than 3.4 million patients have recovered and many countries have gradually restarted their return to the new reality after the implementation of unprecedented non-pharmaceutical interventions such as national lockdowns 2 . Spain has been one of the most affected countries, having reported its highest mortality in Madrid 3 , which has increased by 161% since 2019 4 . The main risk factors for fatality were older age, high blood pressure, overweight and other concomitant conditions 5 .

The information of how COVID-19 infection affects people living with HIV (PLHIV) is still scarce. Several studies support the idea that people living with HIV (PLHIV) could have lower risk of developing severe COVID-19 6-10 , including a lower infection rate, possibly related to the observed in vitro activity of various antiretroviral drugs, particularly protease inhibitors 11-15 , or maybe due to the characteristic immune dysregulation that occurs in PLHIV, which might avoid or limit the cytokine cascade response associated to severe or critical COVID-19 6 .

This study aims to describe the clinical presentation and incidence rate of COVID-19 in PLHIV including patients assisted at hospitals in Madrid. 16 . A case was defined as confirmed when the SARS-CoV-2 PCR was positive in the nasopharyngeal or throat swab. A waiver of consent was granted as only deidentified data were extracted from the medical record. Ethics committee approval was obtained from the institutional review board (EO 091/20).

All research was performed according to the right to privacy, guaranteed as The study reference population data were obtained from the Community of Madrid and the national official register, both globally and by municipality 17, 18 Therefore, our data were compared with the global data of patients attended in the four hospitals, in order to avoid a significant bias, since patients who go to J o u r n a l P r e -p r o o f hospital might have not considered it possible to solve their symptoms by telephone assessment (figure 1). Thus, both HIV positive and negative patients had been treated with the same protocols in the same hospitals. Also, there is a previous report of the first 4,712 consecutive hospitalized patients at these four centers 22 .

Categorical variables were presented with frequencies and were compared using the Fisher's exact test or Pearson's chi-squared test; continuous variables were presented as mean and standard deviation or median and interquartile range (IQR), and were compared using the Student's t test or the Mann-Whitney U test.

Logistic regression was used to test associations among variables and evaluate risk factors for COVID-19 in PLHIV. All statistical analyses were performed using SPSS 20 and a significance level of 0.05 has a similar mean age but showed higher severity, hospitalization, admission to ICU and mortality rates. However, differences are more difficult to assess with a smaller sample and in the absence of data related to subject comorbidities; the J o u r n a l P r e -p r o o f same limitations were found when comparing with the Wuhan 27 and New York 28, 29 cohorts, both with a significantly higher median age. Finally, we found several similarities in our data with a recent systematic review 30 ; then, we suspect that the differences observed between the different cohorts are probably not significant.

Therefore, we consider that the severity of COVID-19 is related to the general characteristics of the population (age and comorbidities) and not to HIV infection, as we observed in global cohorts 31, 32 , and recent prospective [33] [34] [35] and multicenter studies 36 .

Another difference between the two Spanish cohorts lies in the prior antiretroviral treatment for HIV. The antiviral activity of lopinavir / ritonavir described against MERS or SARS 37 , as well as the recently demonstrated efficacy of remdesivir 13 (a nuclotide analog that has similarities to tenofovir), have suggested that patients with HIV infection, on antiretroviral therapy with protease inhibitors or tenofovir (TDF) , may have a lower infection rate or severity 38 . No conclusions can be drawn with our data in this regard. Differences were observed with Casado's and Härter's cohorts 24, 26 , both with a higher prevalence of tenofovir in their patient regimens (73% and 66.7% respectively). Our cohort, has a lower prevalence in TDF-containing regimen (14.8%), more similar to that of Gervasoni (42%) 25 .

Probably due to the sample size, we cannot see significant results in this regard.

Nevertheless, several authors have described the potential activity of tenofovir in SARS-CoV-2 39, 40 and specific studies are required to answer this question.

The main limitation of our study is its retrospective condition, which entails lack of several data. Patients followed-up in our clinic who were admitted for SARS-CoV-2 pneumonia at other facilities could not be included. In addition, data obtained from the Community of Madrid did not include some relevant characteristics, such as age, comorbidities and other conditions, which influence outcomes. Therefore, comparisons with our cohort are restricted. We included both probable and confirmed SARS-CoV-2 infection in the analysis due to the lack of resources for PCR testing in the first weeks of the pandemic in our region. 

The Medical Ethics Committee of the Fundación Jiménez Díaz University

Hospital approved this study. Reference approval number: EO091-020.

AC reports grants and personal fees from ViiV Healthcare, personal fees from Gilead, personal fees from Jannssen, personal fees from Merck, outside the submitted work. MG reports grants and personal fees from ViiV Healthcare, personal fees from Gilead, personal fees from Jannssen, outside the submitted work. 

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Informe n o 32 sobre la situación de

We would like to acknowledge Ignacio Mahillo for his collaboration in the statistical analysis and Drs Sánchez-Verde and Rodríguez de Lema for their contribution to graphical abstract.

AC, BZ and MG conceived the study, participated in its design, data analysis and