To the Editors:
Risk, clinical course, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among patients with HIV-1 infection are still unknown.
Some authors have speculated that HIV-1–infected patients on combination antiretroviral therapy (cART) may have a lower risk for COVID-19 and related complications because of the in vitro activity of some antiretroviral drugs against SARS-CoV-2 and their defective cellular immunity, leading to a decreased possibility of cytokine dysregulation and consequent severe lung damage.1,2 On the contrary, other authors have suggested an increased risk for COVID-19 due to HIV-1–related immunosuppression.3,4 In some recent cohort studies, HIV-infected persons hospitalized for COVID-19 had similar clinical characteristics and outcomes with other hospitalized cohorts of HIV-uninfected patients, and HIV infection on stable cART was not associated with a lower risk of SARS-CoV-2 infection and severe disease.4–10
However, at the moment, there are no data about potential consequences of COVID-19 on immunological and virological parameters of HIV-1–infected persons.
We performed an observational, prospective study of HIV-1–positive patients with SARS-CoV-2 coinfection recruited from our HIV medical clinics in Bologna (Emilia-Romagna region, Italy) between March 1, 2020, and April 15, 2020, to assess changes in their virological and immunological parameters after COVID-19. Overall, 14 adult patients were enrolled into the study, and their characteristics at the moment of COVID-19 diagnosis are summarized in Table 1. All patients gave informed consent.
Nine subjects (64%) were men, the median age was 52.6 years, all were currently treated with cART, and 13 subjects (93%) had plasma HIV RNA below 50 copies/mL. The median current CD4+ T-lymphocyte count [interquartile range (IQR)] was 612 cells/mm3 (339–886), the median current CD8+ T-lymphocyte count (IQR) was 917 cells/mm3 (581–1277), the median CD4/CD8 ratio (IQR) was 0.69 (0.48–0.91), and 2 (14%) had a previous diagnosis of an AIDS-defining condition. Current cART included 1 boosted protease inhibitor (PI) in 4 cases (29%). Nine patients (64%) had one or more comorbidities, including arterial hypertension in 4 cases (29%), type 2 diabetes mellitus in 2 (14%), and obesity in 2 (14%). Concomitant medications included angiotensin-converting enzyme inhibitors in 3 patients (21%).
Diagnosis of COVID-19 was made by detection of SARS-CoV-2 RNA in oropharyngeal and/or nasopharyngeal swab specimens by real-time RT polymerase chain reaction targeting regions in the N gene, following the US Centers for Disease Control and Prevention protocol. Clinical diagnosis was represented by upper respiratory tract infection in 11 cases (79%) and interstitial pneumonia in 3 (21%). At diagnosis, the median duration of symptoms was 4.5 days, and only one patient (7%) had an initial respiratory failure with a PaO2/FiO2 ratio of <300 at arterial blood gas analysis. No cases of acute respiratory distress syndrome with PaO2/FiO2 ratio <200 were observed at diagnosis and during the following observation period. Laboratory workout showed lymphocytopenia (total lymphocyte count less than 1000 cells per 106/L) in 5 patients (36%) and thrombocytopenia (total platelet count less than 150,000 platelets per 106/L) in 3 patients (21%). Only 3 patients (21%) with interstitial pneumonia were hospitalized, whereas other 11 subjects (79%) spent their disease period at home. Clinical recovery was obtained in all patients, while there were no admissions to an intensive care unit and no deaths. Hospitalized patients were discharged after a median (IQR) of 8.3 days (4.2–12.1), and the median global duration of symptoms before clinical recovery (IQR) in all observed patients was 6.8 days (4.2–9.7). Virological recovery was defined by 2 consecutive oropharyngeal and/or nasopharyngeal swab specimens negative for SARS-CoV-2 RNA performed 2–5 weeks after clinical recovery and was obtained in all patients.
The median duration of follow-up (IQR) after the COVID-19 diagnosis was 8.2 weeks (7.1–9.5). At the end of follow-up, the median total lymphocyte count (IQR) was 1609 cells/mm3 (887–2308), the median CD4+ T-lymphocyte count (IQR) was 665 cells/mm3 (391–955), the median CD8+ T-lymphocyte count (IQR) was 886 cells/mm3 (513–1167), and the median CD4/CD8 ratio (IQR) was 0.72 (0.51–0.94). So, median changes (IQR) in immunological parameters were statistically not significant: +49 cells/mm3 (−12, +103) for CD4+ T-lymphocyte count (P = 0.149), −37 cells/mm3 (−81, +22) for CD8+ T-lymphocyte count (P = 0.469), and +0.05 (−0.02, +0.09) for CD4/CD8 ratio (P = 0.818). Patients with plasma HIV RNA <50 copies/mL were 13 (93%), so no patients had virological failure during the observation period.
To the best of our knowledge, our study is the first work investigating potential effects of COVID-19 on immunological and virological status of HIV-1–infected people. At the moment, there are only some data on immunological consequences of COVID-19 among HIV-negative individuals. In several cohorts of patients with SARS-CoV-2 infection, a significant and prolonged lymphopenia has been reported, with a total lymphocyte count returning toward the normal value only 4–6 weeks after diagnosis.11–13 Two retrospective studies involving 21 and 44 HIV-negative patients have shown a significant decrease in the median CD4+ T-lymphocyte count, with a more serious decrease in subjects with severe disease.14,15
Several case series have been already published about clinical course and outcome of COVID-19 in patients with HIV-1 infection, but changes in CD4+ T-cell count and HIV viral load of enrolled patients have not been evaluated.
In a large prospective study performed in Spain, 51 HIV-infected individuals with COVID-19 were described and their characteristics were compared with 1288 HIV-positive patients without COVID-19. Clinical and radiological presentation of COVID-19 in HIV-infected subjects was similar to that observed in the general population, and patients with SARS-CoV-2 coinfection showed a higher body mass index and a greater prevalence of chronic comorbidities than HIV-positive patients without coinfection. In this study, an association between current or nadir CD4+ T-cell count and COVID-19 diagnosis or severity was not found, and no differences were reported in previous use of PIs or other antiretroviral agents in persons with and without COVID-19 diagnosis. The median time (IQR) to SARS-CoV-2 viral clearance in respiratory samples was 18 days (7–28), but changes in CD4+ T-cell count and HIV viremia after COVID-19 were not investigated.4
In a case series of 31 HIV-infected patients hospitalized for COVID-19 in a large tertiary care medical center in New York City, clinical course and outcome were comparable with those reported in other cohorts of HIV-negative individuals. In this series, the mean CD4+ T-cell count and percentage at the time of admission were slightly lower than the normal range, but in an unadjusted comparison, the mean nadir lymphocyte percentage did not differ between HIV-positive and HIV-negative patients.7 However, also in this study, changes in CD4+ T-cell count after COVID-19 diagnosis were not investigated.
In conclusion, in our report, COVID-19 did not produce a significant effect on immunological status and plasma HIV viral load after a median follow-up of 8 weeks in 14 HIV-1–infected patients on stable cART. Obviously, our study has important limitations, including mostly the limited number of patients and the short follow-up.
At the moment, data about effects of SARS-CoV-2 infection on immune–virological parameters in HIV-positive persons with COVID-19 are lacking, so larger cohort studies are needed to better understand characteristics and consequences of SARS-CoV-2 infection in HIV-positive people.
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2. Joob B, Wiwanitkit V. SARS-CoV-2 and HIV. J Med Virol. 2020; published online March 27.
3. Mascolo S, Romanelli A, Carleo MA, et al. Could HIV infection alter the clinical course of SARS-CoV-2 infection? When less is better. J Med Virol. 2020; published online April 15.
4. Vizcarra P, Perez-Elias MJ, Quereda C, et al. Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV. 2020; published online May 28.
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11. Zhao Q, Meng M, Kumar R, et al. Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a systemic review and meta-analysis. Int J Infect Dis. 2020;96:131–135.
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15. Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020; published online March 12.