Immune Deficiency Is a Risk Factor for Severe COVID-19 in People Living With HIV

Christian Hoffmann; José L. Casado; Georg Härter; Pilar Vizcarra; Ana Moreno; Dario Cattaneo; Paola Meraviglia; Christoph D. Spinner; Farhad Schabaz; Stephan Grunwald; Cristina Gervasoni

Disclosures

HIV Medicine. 2021;22(5):372-378. 

In This Article

Abstract and Introduction

Abstract

Objectives: A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID-19 pandemic. Clinical data on patients co-infected with HIV and SARS-CoV-2 are still scarce.

Methods: This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID-19 in people living with HIV (PLWH), infected with SARS-CoV-2 in three countries in different clinical settings. COVID-19 was clinically classified as to be mild-to-moderate or severe.

Results: Of 175 patients, 49 (28%) had severe COVID-19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID-19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/μl, current CD4+ T cells < 350/μl and the presence of at least one comorbidity were significantly associated with severity of COVID-19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS-defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID-19 was a current CD4+ T cell count of < 350/μl (adjusted odds ratio 2.85, 95% confidence interval 1.26–6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir.

Conclusions: In PLWH, immune deficiency is a possible risk factor for severe COVID-19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.

Introduction

In the current COVID-19 pandemic, older age and several comorbidities have been identified as risk factors for severe disease and death, including hypertension, cardiovascular disease and diabetes, but also chronic pulmonary diseases and obesity.[1–4] For people living with HIV (PLWH), preliminary data from the UK, the US and Spain have suggested no elevated incidence of COVID-19.[4–6] However, data on the clinical course of COVID-19 in this population are still scarce. The cellular immune deficiency seen in PLWH is of potential concern as dysfunctional immune responses contribute to disease progression and dysregulated T-cell responses can result in immunopathology.[7] Moreover, there is growing evidence of a transient depletion of T cells during COVID-19, indicating that a pre-existing T-cell depletion induced by HIV may carry deleterious clinical consequences.[8,9] Others groups, however, have speculated that a defective cellular immunity could paradoxically be protective for severe cytokine dysregulation, preventing the cytokine storm seen in severe COVID-19 cases.[10,11] A recent review of five studies found that immunodeficiency was associated with a 1.55-fold increased risk of severe COVID-19 disease. However, the statistical difference was not significant, due to the small numbers of immunodeficient patients.[12]

In our early case series from Italy, Spain and Germany, we described the clinical characteristics of PLWH with COVID-19.[13–15] In all three cohorts, the numbers of patients with severe COVID-19 with severe immune deficiency were too low to draw definite conclusions. Despite the absence of data, according to several organisations such as the British HIV Association (BHIVA), Deutsche AIDS Gesellschaft (DAIG), European AIDS Clinical Society (EACS), Grupo de Estudio del SIDA (GESIDA) and the Polish Scientific AIDS Society,[16] "it has to be assumed that immune suppression, indicated by a low CD4 T-cell count, or not receiving antiretroviral treatment, will be associated with an increased risk for a more severe disease presentation". In order to verify this assumption and to identify potential risk factors for severe disease, we have combined and updated our cohorts of patients with documented HIV and confirmed SARS-CoV-2 infection.

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