The Case Series of 34 Patients with COVID-19 Diagnosed with HIV Infection from Central and Eastern European Countries – Euroguidelines in Central and Eastern Europe Network Group Data

Background: A novel coronavirus (SARS-CoV-2) causing coronavirus disease (COVID-19) was detected at the end of 2019 in China. There are many COVID-19 studies in progress however, little is known about the course of COVID-19 in people living with HIV (PLWH). The aim of our study was to describe epidemiology and clinical characteristics of PLWH diagnosed with COVID-19 reported form Central and Eastern European Countries. Methods: On-line survey was sent to Euroguidelines in Central and Eastern Europe (ECEE) Network Group. Analysis included all conrmed COVID-19 cases between March 11 and June 26 2020 among PLWH in 12 countries: Albania, Belarus, Bosnia and Herzegovina, Bulgaria, Czech Republic, Estonia, Hungary, Lithuania, Poland , Romania, Russia, and Serbia. Results: In total 34 cases were reported. The mean age of those patients was 42.7 years (IQR=35.8-48.5) and most of the patients were male (70.6% vs 29.4%). The mean CD4+ T-cell count prior COVID-19 diagnosis was 558 cells/mm 3 (IQR=312-719) and HIV RNA viral load (VL) was undetectable in 18 of 34 (53%) cases, the data about most recent HIV RNA VL was not available in three cases (8,8%). Comorbidities were observed in 19 (55.9%) patients, mostly cardiovascular disease (27,8%), and in 10 (29.4%) patients had coinfection, mostly chronic hepatitis C (87.5%). The clinical course of COVID-19 was asymptomatic in 4 (12%) cases, mild disease without hospitalization was reported in 11 (32%) cases. Stable patients with respiratory and/or systemic symptoms have been documented in 14 (41%) cases; 5 (15%) patients were clinically unstable with respiratory failure. Full recovery was reported in 31 (91%) cases, two patients died. In one case the data was not available. Conclusion: This study from 12 countries in Central and Eastern Europe region indicates no alarming signals of increased morbidity or mortality from COVID-19 among HIV-positive persons the main limitation of our study is small group of patients. In this study from 12 countries in Central and Eastern Europe region we did see any clear signals of increased morbidity or mortality caused by COVID-19 among HIV-positive persons. As the studies of SARS-CoV-2 among PLWH are performed in small study groups, there is a need for further research.


Introduction
The impact of COVID-19 infection on people living with HIV (PLWH) has not yet been fully understood. There is currently no scienti c evidence suggesting an increased risk of acquiring the infection and a more severe course of the disease in HIV-infected patients, assuming that these patients have normal CD4 T-cell count and are successfully treated with antiretroviral therapy (cART). Generally, it has been clearly con rmed that older people and people with other comorbidities, including cardiovascular disease, type II diabetes and chronic pulmonary diseases are at higher risk of severe COVID-19 in the general population (1). HIV-infected individuals might be at higher risk of COVID-19 infection because signi cant proportion of them are over the age of 50, and the comorbidities such as cardiovascular disease and chronic lung disease are more common than in general population (2)(3)(4). Moreover, little is known about the course of the COVID-19 in PLWH. In our study, we describe epidemiology and clinical characteristics of HIV-positive patients diagnosed with COVID-19 reported form Central and Eastern European Countries.

Material And Methods
The
In our study asymptomatic course of COVID-19 was only seen in 4 (12%) cases, we reported mild disease without hospitalization in 11 (32%) cases. Stable patients with respiratory and/or systemic symptoms have been documented in 14 (41%) cases; we reported 5 (15%) clinically unstable patients with respiratory failure.
Generally, 22 (64,7%) patients were hospitalized. In three patients hospitalization on intensive unit care was needed, two of them were with detectable HIV RNA needed mechanical ventilation -one of these patients died. In our observation full recovery was reported in 31 (91%) cases, two patients died. In one case (2,9%) the data was not available (Table 1).

Discussion
Our review of 34 cases of patients HIV-positive ensured that COVID-19 presents mostly as mild disease in majority of PLWH having full clinical recovery (91%). In the beginning of SARS-CoV-2 pandemic it could be assumed that in the PLWH group, a signi cant proportion of this population had an increased risk of developing a more severe form of COVID-19. This hypothesis was based of fact that PLWH population includes patients with a low CD 4 T cell count (< 200 cells / µl) and patients without cART, and therefore in this group are severely immunocompromised patients. In addition, according to the Centers for Disease Control and Prevention (CDC), the risk of immune suppression is unknown, but for other viral respiratory tract infections, in PLWH population the risk of infection is highest with low CD4 T-cell count and without cART (5). Published data has veri ed those assumptions. The comparable results to our study were reported by Harter et al. In this case series of 33 PLWH patients with COVID-19 infection it was observed that 91% of the patients recovered and 76% of patients have been classi ed as mild cases (6). Another study strongly supports the above data. Study cohort published by Gervasoni et al. consisting of 47 PLWH with COVID-19 infection 96% of patients has fully recovered (7). In the larger study on 51 group of patients HIV-infected diagnosed with COVID − 19 in Madrid Vizcarra et al. found that only six (12%) of studied patients were critically ill, among which two (4%) patients died (8). Other recent studies in small cohorts of patients also strongly support the above data (9).
In our study the most common symptoms of COVID-19 infection were cough in 24 (70,6%), fatigue/malaise in 24 (70,6%) and fever in 21 (61,8%) cases. In the largest description of COVID-19 in Europe, in prospective observational cohort study of 16 479 patients from 166 UK hospitals Docherty et al. presented cough (70%), fever (69%) and shortness of breath (65%) as the most common symptoms. Only four percent of cases reported no symptoms (10). In our review four (12%) patients were asymptomatic, which suggest even better clinical outcome of SARS-CoV-2 in PLWH than in general population.
International AIDS Society (IAS) and the World Health Organization (WHO) recommend PLWH to take the same precautions as the general population, as well as follow speci c governmental recommendations. PLWH who know their serological status but have not yet received cART should have immediate antiretroviral treatment initiated (11). Unfortunately, in Central and Eastern European Countries access to cART is insu cient (12). We observed this fact in our study; only 82.6% of patients were on cART, but despite of that we didn't reported increased morbidity and mortality from COVID-19 among PLWH.
We must admit, that the main limitation of our study is small group of patients. In this study from 12 countries in Central and Eastern Europe region we did not see any clear signals of increased morbidity or mortality caused by COVID-19 among HIV-positive persons. As the studies of SARS-CoV-2 among PLWH are performed in small study groups, there is a need for further research.

Conclusions
This study from 12 countries in Central and Eastern Europe region indicates no alarming signals of increased morbidity or mortality from COVID-19 among HIV-positive persons. There is a need for further research in this eld.