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Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) are prevalent conditions that have been correlated with infertility through overlapped pathophysiological mechanisms. MASLD is associated with metabolic syndrome and is considered among the major causes of chronic liver disease, while PCOS, which is characterized by ovulatory dysfunction and hyperandrogenism, is one of the leading causes of female infertility. The pathophysiological links between PCOS and MASLD have not yet been fully elucidated, with insulin resistance, hyperandrogenemia, obesity, and dyslipidemia being among the key pathways that contribute to liver lipid accumulation, inflammation, and fibrosis, aggravating liver dysfunction. On the other hand, MASLD exacerbates insulin resistance and metabolic dysregulation in women with PCOS, creating a vicious cycle of disease progression. Understanding the intricate relationship between MASLD and PCOS is crucial to improving clinical management, while collaborative efforts between different medical specialties are essential to optimize fertility and liver health outcomes in individuals with MASLD and PCOS. In this review, we summarize the complex interplay between MASLD and PCOS, highlighting the importance of increasing clinical attention to the prevention, diagnosis, and treatment of both entities.
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In this study, we aimed to assess the prevalence of syphilis among people with human immunodeficiency virus (HIV; PWH) engaging in high-risk sexual behavior, determine the stage of syphilis, and evaluate treatment efficacy. A retrospective single-center cohort study was conducted at the AHEPA University General Hospital of Thessaloniki, focusing on PWH at high risk for sexually transmitted infections (STIs) attending outpatient care from January 2019 to December 2022. Sociodemographic and clinical data were collected, incident syphilis rates were identified, associations with HIV-related characteristics were explored, and the treatment response was assessed. Among 991 participants, 94 PWH were diagnosed with syphilis, representing 9.4% of the cohort. Incident syphilis cases experienced a decrease in the early COVID-19 era compared to 2019, followed by a gradual increase leading up to 2022. The majority of syphilis cases were asymptomatic latent syphilis (71.1%). Men who have sex with men (MSM) and younger individuals exhibited higher rates of co-infection during the study period. No significant association was found between incident syphilis and HIV-related factors. Most syphilis cases (86%) were treated with benzathine penicillin G (BPG). Treatment with BPG and doxycycline showed an increased success rate (96.7% vs. 92.9%), with no statistically significant difference observed between them (p = 0.438). This study highlights the alarming incidence of syphilis among PWH engaging in high-risk sexual behavior, particularly among younger MSM. BPG remains effective, and alternative regimens like doxycycline show promise, especially in settings with penicillin shortages or patient allergies.
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Chronic liver disease is one of the main causes of morbidity and mortality in people living with HIV (PLWH). The increasing life expectancy of PLWH, effective treatment for viral hepatitis, and Western dietary patterns as well as the adverse effects of antiretroviral therapy (ART) have rendered metabolic dysfunction-associated steatotic liver disease (MASLD) the most common chronic liver disease in PLWH. The risk factors for MASLD in PLWH include traditional MASLD risk factors and additional virus-specific factors, including the adverse effects of ART. The management of patients suffering from HIV and MASLD is often challenging. Apart from the conventional management of MASLD, there are also certain limitations concerning the use of ART in this patient population. In general, the appropriate combination of antiretroviral drugs should be chosen to achieve the triad of effective viral suppression, avoidance of mitochondrial dysfunction, and deterrence of worsening the patient's metabolic profile. In the current review, we discuss the epidemiology of MASLD in PLWH, the risk factors, and the disease pathogenesis, as well as the limitations in the use of ART in this patient population, while practical recommendations on how to overcome these limitations are also given.
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ABSTRACT: We aimed to evaluate heparin-binding protein (HBP) as a marker of prognosis of unfavorable outcome in COVID-19 pneumonia. This was a post hoc analysis of the SAVE clinical trial investigating anakinra treatment, guided by suPAR (soluble urokinase plasminogen activator receptor) levels ≥6 ng/mL, for the prevention of severe respiratory failure in hospitalized patients with COVID-19 pneumonia. Baseline HBP plasma levels were measured in 534 patients by fluorescence dry quantitative immunoassay using the Jet-iStar 800 analyzer. Concentrations higher than 35 ng/mL predicted 30-day mortality with a moderate specificity of 53.3% and negative predictive value 78.1%; sensitivity was low (29.0%). After multivariate Cox analysis, HBP higher than 35 ng/mL was an independent predictor of 30-day unfavorable outcome (adjusted hazard ratio, 1.77; 95% CI, 1.06-2.94; P = 0.028) and these patients were also at greater risk of death after 90 days (hazard ratio, 1.85; 95% CI, 1.25-2.74; P = 0.002). The cutoff was not predictive of development of severe respiratory failure, septic shock or acute kidney injury. Among patients with baseline HBP levels higher than 35 ng/mL, anakinra treatment was associated with decreased mortality (7.2%) versus comparators (18.1%; P < 0.001). Results confirm that HBP may be an early biomarker of poor outcome among preselected patients at risk from COVID-19 pneumonia.ClinicalTrials.gov registration NCT04357366.
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Péptidos Catiónicos Antimicrobianos , Proteínas Sanguíneas , COVID-19 , Insuficiencia Respiratoria , Humanos , Biomarcadores , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , PronósticoRESUMEN
Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genotyping was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for developing HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.
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Infecciones por VIH , Enfermedades del Sistema Nervioso Periférico , Humanos , Citocinas/genética , Grecia , Marcadores Genéticos , Polimorfismo Genético , Infecciones por VIH/complicaciones , Infecciones por VIH/genética , Infecciones por VIH/epidemiología , Enfermedades del Sistema Nervioso Periférico/epidemiología , Genotipo , Factores de Riesgo , Polimorfismo de Nucleótido SimpleAsunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Riñón , Hipoglucemiantes/farmacología , Glucosa , Sodio/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológicoRESUMEN
The incidence of multidrug-resistant (MDR) bloodstream infections (BSIs) is associated with high morbidity and mortality. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy in endemic regions. Novel diagnostic tests (RDTs) may facilitate and improve patient management. Data were assessed from patients with MDR Gram-negative bacteremia at a university tertiary hospital over a 12-month period. In total, 157 episodes of MDR Gram-negative BSI were included in the study. The overall mortality rate was 50.3%. Rapid molecular diagnostic tests were used in 94% of BSI episodes. In univariate analysis, age (OR 1.05 (95% CI 1.03, 1.08) p < 0.001), Charlson Comorbidity Index (OR 1.51 (95% CI 1.25, 1.83) p < 0.001), procalcitonin ≥ 1(OR 3.67 (CI 95% 1.73, 7.79) p < 0.001), and monotherapy with tigecycline (OR 3.64 (95% CI 1.13, 11.73) p = 0.030) were the only factors associated with increased overall mortality. Surprisingly, time to appropriate antimicrobial treatment had no impact on mortality. MDR pathogen isolation, other than Klebsiella pneumoniae and Acinetobacter baumanii, was associated with decreased mortality (OR 0.35 (95% CI 0.16, 0.79) p = 0.011). In multivariate analysis, the only significant factor for mortality was procalcitonin ≥ 1 (OR 2.84 (95% CI 1.13, 7.11) p = 0.025). In conclusion, in an endemic area, mortality rates in MDR BSI remain notable. High procalcitonin was the only variable that predicted death. The use of rapid diagnostics did not improve mortality rate.
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Background: To date, evidence about sleep disturbances among post-COVID-19 patients is limited. This study aimed to evaluate sleep quality after hospitalization due to SARS-CoV-2 infection. Methods: In-person follow-up was conducted in patients with prior hospitalization due to COVID-19 1(Τ1), 3(Τ2), and 6 (Τ3) months after hospital discharge. Patients were asked to complete questionnaires concerning sleep quality: the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Athens Insomnia Scale (AIS), the Fatigue Severity Scale (FSS), and the Stop-BANG (S-B) questionnaire. Results: In total, 133 patients were enrolled (mean age: 56.0 ± 11.48 years, 59.4% males). The most frequently reported comorbidity was arterial hypertension (29.8% of patients), while 37.4% of patients had no comorbidities. The majority of participants exhibited poor sleep quality (global PSQI ≥ 5) at T1 (84.3%), T2 (75.7%), and T3 (77.4%). Insomnia was observed in 56.5%, 53.5%, and 39.2% of participants, respectively (AIS ≥ 6). An FSS score ≥ 4 was observed in 51.2%, 33.7%, and 29.1% of participants at T1, T2, T3, respectively. Elapsed time was found to be negatively and independently associated with the global PSQI, PSQI C5-Sleep disturbance, PSQI C7-Daytime dysfunctions, FSS, and AIS after adjustment for possible confounders. No significant difference was found between groups with good and poor sleep quality (based on the global PSQI) with respect to gender (p = 0.110), age (p = 0.528), BMI (p = 0.816), smoking status (p = 0.489), hypertension (p = 0.427), severity of disease (p = 0.224), the Charlson Comorbidity Index (p = 0.827), or the length of hospital stay (p = 0.162). Participants with excessive daytime sleepiness (EDS) and patients with severe fatigue (FSS ≥ 4) were significantly younger. Females presented a higher rate of insomnia symptoms (55.7% vs. 44.3%, p < 0.001). Conclusions: Several sleep disturbances were observed after hospital discharge for COVID-19 pneumonia at certain time points; However, the improvement over time was remarkable in most domains of the assessed questionnaires.
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BACKGROUND: Peripheral neuropathy is among the most common complications among people with HIV with prevalence rates varying widely among studies (10-58%). OBJECTIVE: This study aims to assess the prevalence of HIV-associated peripheral neuropathy among HIV-positive people in Northern Greece monitored during the last 5-year period and investigate possible correlations with antiretroviral therapy, disease staging, and potential risk factors, as there is no prior epidemiological record in Greek patients. METHODS: Four hundred twenty patients were divided into a group with peripheral neuropathy (n = 269), and those without (n = 151). Peripheral neuropathy was assessed with a validated Peripheral Neuropathy Screening tool. Statistical analyses were performed with SPSS, were two-tailed, and p-value was set at 0.05. RESULTS: The incidence of peripheral neuropathy was estimated at 35.9%. Age was found to correlate with higher odds of developing HIV-peripheral neuropathy, rising by 4%/year. Females encountered 77% higher probability to develop peripheral neuropathy. Stage 3 of the disease associated with higher occurrence of peripheral neuropathy (96% as compared to stage-1 patients). Among patients with peripheral neuropathy, the duration of antiretroviral therapy was found to be longer than in those without. CONCLUSIONS: Peripheral neuropathy remains one of the most common complications regardless of the antiretroviral-therapy type, indicating the involvement of other risk factors in its occurrence, such as the stage of the disease, age and gender. Therefore, the treating physician should screen patients as early and frequently as possible upon HIV-diagnosis to prevent the progression of this debilitating condition so that prolonged life-expectancy is accompanied by a good quality of life.
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Infecciones por VIH , Enfermedades del Sistema Nervioso Periférico , Antirretrovirales/uso terapéutico , Femenino , Grecia/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Enfermedades del Sistema Nervioso Periférico/epidemiología , Calidad de VidaRESUMEN
OBJECTIVES: The epidemiology of Clostridioides difficile infection (CDI) has undergone many changes since the beginning of this century and continues to evolve based on recent studies. Here, we performed a molecular analysis of C. difficile isolates in northern Greece across 10 health-care facilities, spanning from 2016 to 2019. METHODS: 221 C. difficile isolates were cultured from stool samples of hospitalized patients with diarrhea and screened by PCR for the presence of the toxin A (tcdA), toxin B (tcdB), the binary toxin (cdtA and cdtB) genes and the regulating gene of tcdC. PCR ribotyping of the cultured isolates was performed by a standardized protocol for capillary gel-based PCR ribotyping and an international database with well-documented reference strains. RESULTS: Thirty-five different PCR ribotypes were identified. The most common RTs identified were: 181 (36%, 80/221), 017 (10%, 21/221), 126 (9%, 19/221), 078 (4%, 9/221) and 012 (4%, 8/221). Notably, the predominant RT181, with toxin profile tcdA+tcdB+cdtA+cdtB+, was identified in seven out of ten participating hospitals. CONCLUSIONS: Multiple C. difficile ribotypes have been circulating in the northern Greece region with RTs 181 (closely related to 027), 017, 126 and 078 being predominant.
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Toxinas Bacterianas , Clostridioides difficile , Infecciones por Clostridium , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Clostridioides , Clostridioides difficile/genética , Infecciones por Clostridium/epidemiología , Enterotoxinas/genética , Grecia/epidemiología , Humanos , Reacción en Cadena de la Polimerasa/métodos , RibotipificaciónRESUMEN
The trajectory from moderate and severe COVID-19 into acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation (MV) is a field of active research. We determined serum levels within 24 h of presentation of 20 different sets of mediators (calprotectin, pro- and anti-inflammatory cytokines, interferons) of patients with COVID-19 at different stages of severity (asymptomatic, moderate, severe and ARDS/MV). The primary endpoint was to define associations with critical illness, and the secondary endpoint was to identify the pathways associated with mortality. Results were validated in serial measurements of mediators among participants of the SAVE-MORE trial. Levels of the proinflammatory interleukin (IL)-8, IL-18, matrix metalloproteinase-9, platelet-derived growth factor (PDGF)-B and calprotectin (S100A8/A9) were significantly higher in patients with ARDS and MV. Levels of the anti-inflammatory IL-1ra and IL-33r were also increased; IL-38 was increased only in asymptomatic patients but significantly decreased in the more severe cases. Multivariate ordinal regression showed that pathways of IL-6, IL-33 and calprotectin were associated with significant probability for worse outcome. Calprotectin was serially increased from baseline among patients who progressed to ARDS and MV. Further research is needed to decipher the significance of these findings compared to other acute-phase reactants, such as C-reactive protein (CRP) or ferritin, for the prognosis and development of effective treatments.
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COVID-19 , Síndrome de Dificultad Respiratoria , Calgranulina A , Enfermedad Crítica , Humanos , Interleucinas , Complejo de Antígeno L1 de LeucocitoRESUMEN
The COVID-19 pandemic represents one of the greatest challenges in modern medicine. The disease is characterized by a variable clinical phenotype, ranging from asymptomatic carriage to severe and/or critical disease, which bears poor prognosis and outcome because of the development of severe acute respiratory distress syndrome (SARS) requiring ICU hospitalization, multi-organ failure and death. Therefore, the determination of risk factors predisposing to disease phenotype is of outmost importance. The aim of our study was to evaluate which predisposing factors, including MBL2 genotyping, affected clinical phenotype in 264 COVID-19 patients. We demonstrated that older age along with underlying comorbidities, primarily obesity, chronic inflammatory disorders and diabetes mellitus, represent the most important risk factors related to hospitalization, the development of pneumonia and SARS. Moreover, we found that the presence of the MBL deficiency-causing B allele (rs1800450) was significantly associated with almost 2-fold increased risk for developing pneumonia and requiring hospitalization, suggesting its usage as a molecular predictor of severe disease in SARS-CoV-2 infected individuals.
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COVID-19/genética , Lectina de Unión a Manosa/genética , Adulto , Anciano , Alelos , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
INTRODUCTION: We aimed to compare annual changes in the bone mineral density (BMD) at the lumbar spine (LS) and the femoral neck (FN) in males with HIV-associated osteoporosis treated with either zoledronate (ZOL) or denosumab (Dmab). METHODS: In this open label, 12-month, prospective, multicenter, cohort study, 23 male people living with HIV (PLWH) under antiretroviral therapy (ART) with low BMD were administered either a single iv infusion of ZOL 5 mg (n = 10) or Dmab 60 mg sc injections biannually (n = 13). Fourteen age-matched male PLWH with normal BMD served as controls. BMD was measured at baseline and at 12 months. RESULTS: LS-BMD increased within both treatment groups at 12 months (ZOL 5.43% ± 3.60%, p = 0.001; Dmab 5.76% ± 3.44%, p < 0.005) and decreased in controls (-2.58% ± 4.12, p = 0.04). FN-BMD increased in both treatment groups at 12 months (ZOL 7.23% ± 5.46%, p = 0.003; Dmab 3.01% ± 2.46%, p < 0.005), and remained unchanged in controls (1.22% ± 2.09, p = 0.06). LS-BMD changes did not differ between the two treatment groups, but FN-BMD changes were more prominent in the ZOL group (p < 0.05). None of our study cohort sustained new fragility fractures during the 12-month study period, and no case of acute phase response was recorded in the ZOL group. CONCLUSIONS: In male PLWH under ART requiring osteoporosis treatment both ZOL and Dmab are efficient and well tolerated therapeutic options achieving BMD increases at least for the first year of treatment.
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Former studies have revealed intersex variability in immune response to infectious diseases, including Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological surveillance of the ongoing pandemic has demonstrated a male vulnerability to morbidity and mortality, despite similar infection rates between the two sexes. Divergence in the frequency of comorbidities between males and females, differences in hormonal profile, chromosomal composition and gender behavior have all been proposed as potential causative factors. Data deriving from the immunization process indirectly support the existence of a sex-specific response to SARS-CoV-2, since females apparently produce higher numbers of antibodies while simultaneously exhibiting higher rates of side effects, indicating a stronger immune reactivity to the vaccine's elements. Interpreting intersex differences in immune response to SARS-CoV-2 could lead to a deeper understanding of the COVID-19 pathophysiology and enable healthcare professionals to conduct a more accurate patient risk assessment and better predict the clinical outcome of the disease. This narrative review aims to discuss the pathophysiological and behavioral basis of the disproportionate male morbidity and mortality observed in COVID-19, in the context of most research findings in the field.
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COVID-19 , Índice de Severidad de la Enfermedad , Caracteres Sexuales , COVID-19/fisiopatología , Cromosomas Humanos X , Femenino , Hormonas Esteroides Gonadales , Humanos , Masculino , SARS-CoV-2 , Sexismo , VacunaciónRESUMEN
A significant proportion of people infected with SARS-CoV-2 report a new onset of smell or taste loss. The duration of the chemosensory impairment and predictive factors of recovery are still unclear. We aimed to investigate the prevalence, temporal course and recovery predictors in patients who suffered from varying disease severity. Consecutive adult patients diagnosed to be infected with SARS-CoV-2 via reverse-transcription-polymerase chain reaction (RT-PCR) at two coronavirus disease-2019 (COVID-19) Reference Hospitals were contacted to complete a survey reporting chemosensory loss, severity, timing and duration, nasal symptoms, smoking, allergic rhinitis, chronic rhinosinusitis, comorbidities and COVID-19 severity. In a cross-sectional study, we contacted 182 patients and 150 responded. Excluding the critically ill patients, 38% reported gustatory and 41% olfactory impairment (74% severe/anosmia). Most of the patients (88%) recovered their sense of smell by two months (median: 11.5 days; IQR: 13.3). For 23%, the olfactory loss lasted longer than a month. There were no significant differences in the prevalence and duration of chemosensory loss between groups of varying COVID-19 severity, and sexes (all p > 0.05). Moderate hyposmia resolved quicker than more severe loss (p = 0.04). Smell and taste loss are highly prevalent in COVID-19. Most patients recover fast, but nearly one out of ten have not recovered in two months.
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COVID-19/epidemiología , Pandemias , COVID-19/mortalidad , Comorbilidad , Trazado de Contacto , Femenino , Grecia/epidemiología , Hospitalización , Humanos , Masculino , SARS-CoV-2RESUMEN
Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.
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COVID-19 , Diabetes Mellitus , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Glucemia , Glucosa , Humanos , SARS-CoV-2 , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19. Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied. Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata. Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance. Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme. Clinical trial number: NCT04357366.
People infected with the SARS-CoV-2 virus, which causes COVID-19, can develop severe respiratory failure and require a ventilator to keep breathing, but this does not happen to every infected individual. Measuring a blood protein called suPAR (soluble urokinase plasminogen activator receptor) may help identify patients at the greatest risk of developing severe respiratory failure and requiring a ventilator. Previous investigations have suggested that measuring suPAR can identify pneumonia patients at highest risk for developing respiratory failure. The protein can be measured by taking a blood sample, and its levels provide a snapshot of how the body's immune system is reacting to infection, and of how it may respond to treatment. Anakinra is a drug that forms part of a class of medications called interleukin antagonists. It is commonly prescribed alone or in combination with other medications to reduce pain and swelling associated with rheumatoid arthritis. Kyriazopoulou et al. investigated whether treating COVID-19 patients who had developed pneumonia with anakinra could prevent the use of a ventilator and lower the risk of death. The findings show that treating COVID-19 patients with an injection of 100 milligrams of anakinra for ten days may be an effective approach because the drug combats inflammation. Kyriazopoulou et al. examined various markers of the immune response and discovered that anakinra was able to improve immune function, protecting a significant number of patients from going on a ventilator. The drug was also found to be safe and cause no significant adverse side effects. Administering anakinra decreased of the risk of progression into severe respiratory failure by 70%, and reduced death rates significantly. These results suggest that it may be beneficial to use suPAR as an early biomarker for identifying those individuals at highest risk for severe respiratory failure, and then treat them with anakinra. While the findings are promising, they must be validated in larger studies.