Phylodynamic evolution of HIV-1 A6 sub-subtype epidemics in Poland.

The human immunodeficiency virus type 1 (HIV-1) A6 sub-subtype is highly prevalent in Eastern Europe. Over the past decade, the dissemination of the A6 lineage has been expanding in Poland. The recent Russian invasion of Ukraine may further escalate the spread of this sub-subtype. While evolutionary studies using viral sequences have been instrumental in identifying the HIV epidemic patterns, the origins, and dynamics of the A6 sub-subtype in Poland remain to be explored. We analyzed 1185 HIV-1 A6 pol sequences from Poland, along with 8318 publicly available sequences from other countries. For analyses, phylogenetic tree construction, population dynamics inference, Bayesian analysis, and discrete phylogeographic modeling were employed. Of the introduction events to Poland, 69.94% originated from Ukraine, followed by 29.17% from Russia. Most A6 sequences in Poland (53.16%) formed four large clades, with their introductions spanning 1993-2008. Central and Southern Polish regions significantly influenced migration events. Transmissions among men who have sex with men (MSM) emerged as the dominant risk group for virus circulation, representing 72.92% of migration events. Sequences from migrants were found primarily outside the large clades. Past migration from Ukraine has fueled the spread of the A6 sub-subtype and the current influx of war-displaced people maintains the growing national epidemic.

Circulation of Human Immunodeficiency Virus 1 A6 Variant in the Eastern Border of the European Union-Dynamics of the Virus Transmissions Between Poland and Ukraine.

BACKGROUND: The human immunodeficiency virus (HIV) type 1 A6 variant is dominating in high-prevalence Eastern European countries, with increasing prevalence over the remaining regions of Europe. The recent war in Ukraine may contribute to further introductions of this A6 lineage. Our aim was to model the transmission dynamics of the HIV-1 A6 variant between Poland and Ukraine. METHODS: HIV-1 A6 partial pol sequences originating from Poland (n = 1185) and Ukraine (n = 653) were combined with publicly available sequences (n = 7675) from 37 other countries. We used maximum likelihood-based tree estimation followed by a bayesian inference strategy to characterize the putative transmission clades. Asymmetric discrete phylogeographic analysis was used to identify the best-supported virus migration events across administrative regions of Poland and Ukraine. RESULTS: We identified 206 clades (n = 1362 sequences) circulating in Poland or Ukraine (63 binational clades, 79 exclusively Polish, and 64 exclusively Ukrainian). Cross-border migrations were almost exclusively unidirectional (from Ukraine to Poland, 99.4%), mainly from Eastern and Southern Ukraine (Donetsk, 49.7%; Odesa, 17.6% regions) to the Central (Masovian, 67.3%; Lodz, 18.2%) and West Pomeranian (10.1%) districts of Poland. The primary sources of viral dispersal were the Eastern regions of Ukraine, long affected by armed conflict, and large population centers in Poland. CONCLUSIONS: The Polish outbreak of the A6 epidemic was fueled by complex viral migration patterns across the country, together with cross-border transmissions from Ukraine. There is an urgent need to include war-displaced people in the national HIV prevention and treatment programs to reduce the further spread of transmission networks.

Clinical Perspective on Human Immunodeficiency Virus Care of Ukrainian War Refugees in Poland.

BACKGROUND: The Russian invasion of Ukraine forced migration for safety, protection, and assistance. Poland is the primary sheltering country for Ukrainian refugees, providing support including medical care, which resulted in the rapid ∼15% increase in the number of followed-up people with human immunodeficiency virus (HIV) (PWH) in the country. Here, we present the national experience on HIV care provided for refugees from Ukraine. METHODS: Clinical, antiretroviral, immunological, and virologic data from 955 Ukrainian PWH entering care in Poland since February 2022 were analyzed. The dataset included both antiretroviral-treated (n = 851) and newly diagnosed (n = 104) patients. In 76 cases, protease/reverse transcriptase/integrase sequencing was performed to identify drug resistance and subtype. RESULTS: Most (70.05%) of the patients were female, with a predominance of heterosexual (70.3%) transmissions. Anti-hepatitis C antibody and hepatitis B antigen were present in 28.7% and 2.9% of the patients, respectively. A history of tuberculosis was reported in 10.1% of cases. Among previously treated patients, the viral suppression rate was 89.6%; 77.3% of newly HIV diagnosed cases were diagnosed late (with lymphocyte CD4 count <350 cells/µL or AIDS). The A6 variant was observed in 89.0% of sequences. Transmitted mutations in the reverse transcriptase were found in 15.4% treatment-naive cases. Two patients with treatment failure exhibited multiclass drug resistance. CONCLUSIONS: Migration from Ukraine influences the characteristics of HIV epidemics in Europe, with an increase in the proportion of women and hepatitis C coinfected patients. Antiretroviral treatment efficacy among previously treated refugees was high, with new HIV cases frequently diagnosed late. The A6 subtype was the most common variant.

Immune restoration affects 10-year survival in people living with HIV/AIDS.

INTRODUCTION: In recent years, a reduction in the life expectancy gap between people living with HIV (PLWH) and the general population has been observed, irrespective of CD4 lymphocyte count, due to widespread access to antiretroviral treatment. The increase in the life expectancy of PLWH has increased awareness of both the ageing process and gender discrepancies in immune restoration and survival. MATERIALS AND METHODS: Longitudinal data were collected for 2240 patients followed up at the Hospital for Infectious Diseases in Warsaw, Poland (n = 1482), and the Department of Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland (n = 758). Immune restoration was measured from the time of starting combination antiretroviral therapy until achieving 500 CD4 lymphocytes/µL, 800 CD4 lymphocytes/µL, and CD4/CD8 lymphocyte ratios of > 0.8 and > 1.0. Full recovery was achieved when the patient was restored to both 800 CD4 lymphocytes/µL and a CD4/CD8 lymphocyte ratio > 1.0. RESULTS: For all endpoints, immune restoration had a protective effect by reducing mortality. Patients who achieved immune restoration had a greater chance of reduced mortality than those who did not achieve immune restoration: for CD4 count > 500 cells/µL, HR = 5.4 (interquartile range: 3.09-9.41), p < 0.001; for CD4 > 800 cells/µL, HR = 5.37 (2.52-11.43), p < 0.001; for CD4/CD8 ratio > 0.8, HR = 3.16 (1.81-5.51), p < 0.001; for CD4/CD8 ratio > 1.0, HR = 2.67 (1.49-5.24), p = 0.001, and for full immune recovery, HR = 3.62 (1.63-8.04), p = 0.002. CONCLUSIONS: Immune restoration remains a powerful factor in improving the survival of PLWH, regardless of the speed of recovery.

Detection of Polish cases of highly virulent subtype B of HIV-1 originating in the Netherlands.

Infection with the human immunodeficiency virus type 1 (HIV-1) subtype B is most commonly acquired in Poland through men who have sex with men (MSM) comparable to the HIV epidemic in the Netherlands. Following a paper by Chris Wymant et al. on February 4, 2022 in Science on a highly virulent variant of HIV-1 subtype-B (VB-variant) in the Netherlands raised concerns about the possibility of the variant dissemination to other European countries. We aim to report the spread of HIV-1 VB-variant, recently identified in the Netherlands, into other European regions. Subtype B pol gene fragments of protease (P), reverse transcriptase (RT), and integrase (IN) from our laboratory supplemented with publicly available sequences were inferred with VB samples from the Netherlands. For positively clustering samples, clinical observations were compiled. Between May 2009 and August 2014, three cases of VB sequences of Polish origin and one additional from Belgium were identified. Patients presented with elevated viral loads and fast CD4 decline as original characteristics. The mean number of base substitutions per site within the clade versus interclade variability showed a high intragroup sequence similarity, reflecting an ongoing MSM transmission cluster for Polish sequences. The sampling period coincides with the ongoing Dutch VB-variant spread reported between 2003 and 2014. This study informs on phylogenetic descriptions, and clinical symptoms from the rare and emerging VBs placed in Poland. VB is not expanding since 2014 and the Inviduals infected with the VB virus can be treated successfully. Studies on the propagation of novel and potentially virulent virus variants in the undersampled regions add to the understanding of the pan-European HIV-1 transmission dynamics.

Artificial neural network based prediction of the lung tissue involvement as an independent in-hospital mortality and mechanical ventilation risk factor in COVID-19.

INTRODUCTION: During COVID-19 pandemic, artificial neural network (ANN) systems have been providing aid for clinical decisions. However, to achieve optimal results, these models should link multiple clinical data points to simple models. This study aimed to model the in-hospital mortality and mechanical ventilation risk using a two step approach combining clinical variables and ANN-analyzed lung inflammation data. METHODS: A data set of 4317 COVID-19 hospitalized patients, including 266 patients requiring mechanical ventilation, was analyzed. Demographic and clinical data (including the length of hospital stay and mortality) and chest computed tomography (CT) data were collected. Lung involvement was analyzed using a trained ANN. The combined data were then analyzed using unadjusted and multivariate Cox proportional hazards models. RESULTS: Overall in-hospital mortality associated with ANN-assigned percentage of the lung involvement (hazard ratio [HR]: 5.72, 95% confidence interval [CI]: 4.4-7.43, p < 0.001 for the patients with >50% of lung tissue affected by COVID-19 pneumonia), age category (HR: 5.34, 95% CI: 3.32-8.59 for cases >80 years, p < 0.001), procalcitonin (HR: 2.1, 95% CI: 1.59-2.76, p < 0.001, C-reactive protein level (CRP) (HR: 2.11, 95% CI: 1.25-3.56, p = 0.004), glomerular filtration rate (eGFR) (HR: 1.82, 95% CI: 1.37-2.42, p < 0.001) and troponin (HR: 2.14, 95% CI: 1.69-2.72, p < 0.001). Furthermore, the risk of mechanical ventilation is also associated with ANN-based percentage of lung inflammation (HR: 13.2, 95% CI: 8.65-20.4, p < 0.001 for patients with >50% involvement), age, procalcitonin (HR: 1.91, 95% CI: 1.14-3.2, p = 0.14, eGFR (HR: 1.82, 95% CI: 1.2-2.74, p = 0.004) and clinical variables, including diabetes (HR: 2.5, 95% CI: 1.91-3.27, p < 0.001), cardiovascular and cerebrovascular disease (HR: 3.16, 95% CI: 2.38-4.2, p < 0.001) and chronic pulmonary disease (HR: 2.31, 95% CI: 1.44-3.7, p < 0.001). CONCLUSIONS: ANN-based lung tissue involvement is the strongest predictor of unfavorable outcomes in COVID-19 and represents a valuable support tool for clinical decisions.

Overcoming Geographical Constraints: A Diagnostic and Therapeutic Challenge of Amebic Liver Abscess in a Non-Endemic Region.

This case report provides data on unique challenges related to amoebiasis diagnostics and treatment in non-endemic regions. The presented case report is focused a 28-year-old male patient of Indian origin, temporarily living in Poland, who was diagnosed with an amoebic liver abscess. The patient presented with a range of non-specific symptoms including shortness of breath, chest pain, and fever. The differential diagnosis included cardio-pulmonary diseases, a range of tropical diseases such as malaria or typhoid fever, bacterial abscesses, and malignancies, necessitating a comprehensive, multi-modal diagnostic approach. This approach included an extensive review of patient history, physical examination, and various laboratory and imaging investigations. A further challenge in this case was the unavailability of standard cysticidal treatments in Poland, which required individualized therapeutic strategy. Despite these obstacles, the patient was successfully treated using an alternative regimen of intravenous metronidazole, ceftriaxone, doxycycline, chloroquine, and finally, trimethoprim/sulfamethoxazole (treatment with metronidazole was used as a base drug, due to the lack of typical cysticidal treatment, an alternative treatment was added: chloroquine is a recommended drug used in the treatment of pregnant patients, in addition, doxycycline showed in vitro activity against Entamoeba histolytica). This therapeutic journey underscored the value of adaptability in treatment protocols, particularly in regions where certain resources may not be readily available. This case report underlines the importance of broadening the differential diagnosis in non-endemic regions to include tropical diseases, particularly in the context of increasing global travel and migration. It also highlights the significance of employing comprehensive diagnostic strategies and adaptable treatment protocols in such scenarios. In addition, the report reiterates the need for global collaboration and education among healthcare providers to effectively manage tropical diseases, especially in non-endemic regions. Through its exploration of the complexities associated with diagnosing and managing amebiasis in a non-endemic region, this report offers valuable insights to clinicians worldwide.

Cardiovascular Risk in People Living with Human Immunodeficiency (HIV) Viremia Suppression in a Young, Mid-Eastern European Population - Preliminary Study.

Purpose: People living with HIV are twice as likely to develop cardiovascular diseases (CVDs) and myocardial infarction related to atherosclerosis than the uninfected population. This study aimed to evaluate the prevalence of subclinical atherosclerosis in a young, mid-eastern European population of PLWH receiving ART for undetectable viremia. Patients and Methods: This was a single-centre study. We included 34 patients below 50 years old, treated in Szczecin, Poland, with confirmed HIV-1 infection, treated with antiretroviral therapy (ART), and undetectable viremia. All patients underwent coronary artery computed tomography (CACT), carotid artery intima-media thickness (IMT) evaluation, and echocardiography. Results: In the primary assessment, only two (5.8%) patients had an increased CVD risk calculated using the Framingham Risk Score (FRS), but we identified coronary or carotid plaques in 26.5% of the patients. Neither traditional risk factors nor those associated with HIV significantly influenced the presence of the plaque. IMT was significantly positively correlated with age and the FRS (R=0.38, p=0.04). Relative wall thickness assessed in echocardiography was higher in those with plaque (0.49 vs 0.44, p=0.04) and significantly correlated with IMT (R=0.38, p=0.04). Conclusion: In our population, more than a quarter of PLWH with undetectable viremia had subclinical atherosclerosis in either the coronary or carotid arteries. The FRS underpredicted atherosclerosis in this population. The role of RWT as a possible early marker of atherosclerosis needs further studies.

Unveiling the Heart of the Matter: Echocardiographic Insights into Diastolic Function and Left Ventricular and Atrial Changes in HIV Patients with Controlled Viremia.

BACKGROUND: People living with human immunodeficiency virus (HIV) (PLWH) have increased risk of developing diastolic dysfunction (DD) and heart failure with preserved ejection fraction (EF). In this observational study, we evaluated DD and left ventricular hypertrophy (LVH) in PLWH receiving antiretroviral therapy (ART) with undetectable viremia. METHODS: We conducted an observational study. All participants underwent transthoracic echocardiography to assess chamber size and systolic and diastolic function. RESULTS: Most patients showed concentric remodeling without LVH. All patients had normal left ventricle systolic function (EF median 61.3%, interquartile range: 57.8-66.2). None fulfilled the DD criteria, while two patients (6%) had undetermined diastolic function. Twenty percent (n = 7) of patients had an enlarged left atrium (left atrium volume index [LAVI] > 34 cm3/m2). These patients had a significantly lower CD4+ count (771.53 ± 252.81 vs. 446.00 ± 219.02, p = 0.01) and higher relative wall thickness (0.50 ± 0.05 vs. 0.44 ± 0.06, p = 0.03). Patients without immune restoration above 500 cells/µL had significantly higher LAVI (33.92 ± 6.63 vs. 24.91 ± 7.03, p = 0.01). CONCLUSIONS: One-fifth of patients had left atrial enlargement associated with worse immune restoration during ART treatment. The mechanism of left atrial enlargement and its association with cardiovascular risk require further investigations.

HIV Care in Ukrainian Migrants in Two European Countries: All the Same?

Introduction: War in Ukraine prompted an enormous refugee influx into Europe, including approximately 4200 people with HIV. The unique healthcare features of Ukrainian refugees living with HIV were compared between two infectious disease departments in Bonn, Germany, and Szczecin, Poland. Methods: This is a retrospective study on 161 people living with HIV (PLWH) refugees from Ukraine seeking care in Bonn (n = 30) and Szczecin (n = 131) between April 2022 and May 2023. Demographic, virologic, immunologic, and coinfection data were analyzed. Results: The majority of the studied individuals were female: 64% (n = 84) in Szczecin and 60% (n = 18) in Bonn. The main HIV transmission mode was heterosexual sex in 73.5% (n = 114). All were on combined antiretroviral therapy (cART) on arrival, primarily on the TLD regimen (TDF/3TC/DTG) (68.4%, n = 106). In Germany, cART was most frequently switched to BIC/TAF/FTC in 83.4% (n = 25); in Poland, the most common combination was TDF/FTC + DTG (58%, n = 76). A prevalence of replicating hepatitis C was in 11.7% (n = 15), and that for chronic hepatitis B (HBV) was in 4.7% (n = 4). History of past tuberculosis was reported in 16.9% (n = 14, Poland, and n = 7, Germany). Follow-up after 6 months showed immunological reconstitution with a mean increase of CD4+ of 10 (IQR: -69.5-120.5) cells/µL in Poland and 51.5 (IQR: -22.5-135.5) cells/µL in Germany; p = 0.04. Virologic suppression (<40 HIV-RNA/mL) was high in care entry (n = 62; 98%) for Poland, and n = 26 (92.6%) for Germany, and suppression was achieved in the majority of patients in the 6-month control (89.7% in Poland vs. 95.7% in Germany). Conclusions: Health challenges posed by war migration extend beyond HIV to coinfections as HBV, HCV, and tuberculosis give an indication for a broader search for coinfections, often less common in the new country.

Phylodynamic Dispersal of SARS-CoV-2 Lineages Circulating across Polish-German Border Provinces.

Introduction: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evolved into a worldwide outbreak, with significant molecular evolution over time. Large-scale phylodynamic studies allow to map the virus spread and inform preventive strategies. Aim: This study investigates the extent of binational dispersal and dynamics of SARS-CoV-2 lineages between seven border provinces of the adjacent countries of Poland and Germany to reconstruct SARS-CoV-2 transmission networks. Methods: Following three pandemic waves from March 2020 to the end of May 2021, we analysed a dataset of 19,994 sequences divided into B.1.1.7|Alpha and non-Alpha lineage groups. We performed phylogeographic analyses using the discrete diffusion models to identify the pathways of virus spread. Results: Based on population dynamics inferences, in total, 673 lineage introductions (95% HPD interval 641−712) for non-Alpha and 618 (95% HPD interval 599−639) for B.1.1.7|Alpha were identified in the area. For non-Alpha lineages, 5.05% binational, 86.63% exclusively German, and 8.32% Polish clusters were found, with a higher frequency of international clustering observed for B.1.1.7|Alpha (13.11% for binational, 68.44% German and 18.45% Polish, p < 0.001). We identified key transmission hubs for the analysed lineages, namely Saxony, West Pomerania and Lower Silesia. Conclusions: Clustering patterns between Poland and Germany reflect the viral variant transmission dynamics at the international level in the borderline area. Tracing the spread of the virus between two adjacent large European countries may provide a basis for future intervention policies in cross-border cooperation efforts against the spread of the pandemics.

Clinical parameters, selected HLA and chemokine gene variants associated with late presentation into care of people living with HIV/AIDS.

INTRODUCTION: Late presentation into care remains a significant problem in the diagnosis of HIV infection, and may negatively impact the Joint United Nations Program HIV/AIDS elimination targets. Host genetics affects the tempo of HIV disease progression and therefore may influence clinical status at care entry. MATERIALS AND METHODS: Longitudinal data were collected for 863 Caucasian patients followed up at Pomeranian Medical University, Szczecin, Poland. Single nucleotide polymorphisms in CCR2 (rs1799864), CX3CR1 (rs3732378), HLAC-35 (rs9264942), CCR5 promoter (rs1799988) as well as 32 base pair CCR5 mutation and HLA-B*5701 genotypes were correlated with the clinical and immunologic patient status at care entry. Late presentation was defined as baseline CD4 lymphocyte count <350 cells/µL or history of AIDS-defining illness, while advanced HIV disease as baseline CD4 lymphocyte count <200 cells/µL or AIDS. RESULTS: Of the analyzed gene variants, the CCR2 (rs1799864) GG genotype was more frequent among patients presenting for care with a CD4 lymphocyte count <200/µL (82.6% for GG homozygotes vs. 74.5% for allele A carriers, p = 0.01). The presence of the heterozygous wt/Δ32 genotype at the CCR5 gene was associated with a higher frequency of asymptomatic infection (18.9% for wt/Δ32 heterozygotes vs. 12% for wt/wt homozygotes, p = 0.03). As expected, this association was also observed among late presenters compared to patients presenting for care earlier (13.7% vs. 19,7%, respectively, p = 0.04). Finally, HLA-B*5701 was less common among late presenters (5%) compared to patients who entered care early (9.6%, p = 0.01) or patients with advanced HIV disease (8.9% vs. 5.2%, p = 0.02). CONCLUSIONS: Late presentation was associated with the GG homozygous genotype at the CCR2 rs1799864 SNP, while both the HLA-B*5701 variant and the CCR5 wt/Δ32 were associated with more favorable clinical profile at care entry.

Tocilizumab Use among Patients Who Developed Pulmonary Embolism in the Course of Cytokine Release Storm and COVID-19 Pneumonia-A Retrospective Study.

INTRODUCTION: Thromboembolic events, including mainly pulmonary embolisms and ischemic strokes, occur in up to one-third of COVID-19 patients. As efficacy of tocilizumab (TCZ) among patients with acute pulmonary embolism (PE) was not previously investigated, this study aimed to provide such data. OBJECTIVES: The aim of the study was to investigate the effect of TCZ on mortality in patients with confirmed acute pulmonary embolism, cytokine release storm and COVID-19 pneumonia. PATIENTS AND METHODS: Longitudinal data of 4287 patients with confirmed SARS-CoV-2 infection were collected between 4 March 2020 and 16 January 2022. In this study, we retrospectively analyzed the samples and dataset of cases with confirmed acute pulmonary embolism associated with at least moderate lung involvement due to COVID-19 pneumonia. RESULTS: In the analyzed dataset, 64 adult patients were diagnosed with PE, and of these, 28 (44%) cases were treated with two 8 mg/kg doses of TCZ, and 36 (56%) did not receive this agent. The groups were balanced regarding demographics, comorbidities and the biochemical markers. Overall mortality in our study was 29.6% (n = 17). Mortality in the group treated with TCZ was 43% (n = 12) compared to 19% (n = 7) in the group without TCZ. In multivariate proportional Cox hazards models, intravenous administration of TCZ was independently associated with higher mortality (HR: 3.342 (CI: 1.077-10.370), p = 0.036). CONCLUSIONS: In patients with COVID-19 pneumonia with at least moderate lung involvement, CRS and acute pulmonary embolism, administration of TCZ is associated with increased mortality. Therefore, TCZ should be used with caution in SARS-CoV-2 cases with pulmonary embolism.

Correction: Influence of HLA-B*5701 on 20 year survival rate among patients living with HIV.

[This corrects the article DOI: 10.1371/journal.pone.0255834.].

Factors Influencing Immune Restoration in People Living with HIV/AIDS.

Introduction: Immune restoration is a key clinical aspect that is pursued in the care of human immunodeficiency virus (HIV)-infected patients. Despite effective antiretroviral treatment and undetectable viremia, immune recovery is often incomplete. Materials and methods: Data from 311 Caucasian patients were collected. SNP in CCR2(rs1799864), CX3CR1(rs3732378), HLAC-35(rs9264942), and CCR5(promoter, rs1799988); a 32bp deletion(Δ32) in CCR5; and HLA-B*5701 genotypes were correlated with clinical data and selected endpoints. Kaplan−Meier and Cox proportional hazards models were used to analyze the effects of genetic factors over time. Results: For HLA-B*5701, the effect on the CD4+/CD8+ >0.8 cell ratio was lost within 48 months (HR = 2.04, 95% CI: 1.04−4.03), and the effect on the CD4+ cell count >500 cells/µL was lost within 12 months (HR = 2.12, CI: 1.11−4.04). The effect of CCR2 GG on the CD4+/CD8+ >0.8 cell ratio was lost within 36 months (HR = 1.7, CI: 1.05−2.75). For CCR5 wt/Δ32, the effect on the CD4+/CD8+ >1.0 cell ratio was lost within 24 months (HR = 2.0, CI: 1.08−3.69), and the effect on the CD4+ >800 cells/µL cell count was lost within 18 months (HR = 1.98, CI: 1.14−4.73). Conclusions: Selected genetic polymorphisms, namely CCR2 GG and CCR5 Δ32, and the presence of the HLA-B*5701 allele positively influenced immune restoration in cART-treated patients with HIV/AIDS.

Programmed Cell Death-1/Programmed Cell Death-1 Ligand as Prognostic Markers of Coronavirus Disease 2019 Severity.

Current research proves that immune dysregulation is a common feature of coronavirus disease 2019 (COVID-19), and immune exhaustion is associated with increased disease mortality. Immune checkpoint molecules, including the programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) axis, may serve as markers of disease severity. Accordingly, in this study, we evaluated the expression of PD-1/PD-L1 in patients with COVID-19. Blood immunophenotypes of hospitalized patients with moderate (n = 17, requiring oxygen support) and severe (n = 35, requiring mechanical ventilation in the intensive care setting) COVID-19 were compared and associated with clinical, laboratory, and survival data. The associations between severity and lymphocyte profiles were analysed at baseline and after 7 and 14 days of in-hospital treatment. Forty patients without COVID-19 infection were used as controls. For PD-1-positive T and B lymphocyte subsets, notable increases were observed between controls and patients with moderate or severe COVID-19 for CD4+PD-1+ T cells, CD8+PD-1+ T and CD19+PD-1+ B cells. Similar trends were observed for PD-L1-positive lymphocytes, namely, CD4+PD-L1+ T cells, CD8+PD-L1+ T cells and CD19+PD-L1+ B cells. Importantly, all markers associated with PD-1 and PD-L1 were stable over time for the analysed time points in the moderate and severe COVID-19 groups. Increased abundances of PD-1+ and PD-L1+ lymphocytes were associated with disease severity and mortality and were stable over time in patients with moderate to severe COVID-19. These immune exhaustion parameters may be attractive biomarkers of COVID-19 severity.