Nebulised interferon-ß1a (SNG001) in hospitalised COVID-19: SPRINTER phase III study.

Background: Despite the availability of vaccines and therapies, patients are being hospitalised with coronavirus disease 2019 (COVID-19). Interferon (IFN)-ß is a naturally occurring protein that stimulates host immune responses against most viruses, including severe acute respiratory syndrome coronavirus 2. SNG001 is a recombinant IFN-ß1a formulation delivered to the lungs via nebuliser. SPRINTER assessed the efficacy and safety of SNG001 in adults hospitalised due to COVID-19 who required oxygen via nasal prongs or mask. Methods: Patients were randomised double-blind to SNG001 (n=309) or placebo (n=314) once daily for 14 days plus standard of care (SoC). The primary objective was to evaluate recovery after administration of SNG001 versus placebo, in terms of times to hospital discharge and recovery to no limitation of activity. Key secondary end-points were progression to severe disease or death, progression to intubation or death and death. Results: Median time to hospital discharge was 7.0 and 8.0 days with SNG001 and placebo, respectively (hazard ratio (HR) 1.06 (95% CI 0.89-1.27); p=0.51); time to recovery was 25.0 days in both groups (HR 1.02 (95% CI 0.81-1.28); p=0.89). There were no significant SNG001-placebo differences for the key secondary end-points, with a 25.7% relative risk reduction in progression to severe disease or death (10.7% and 14.4%, respectively; OR 0.71 (95% CI 0.44-1.15); p=0.161). Serious adverse events were reported by 12.6% and 18.2% patients with SNG001 and placebo, respectively. Conclusions: Although the primary objective of the study was not met, SNG001 had a favourable safety profile, and the key secondary end-points analysis suggested that SNG001 may have prevented progression to severe disease.

Nebulised interferon beta-1a (SNG001) in hospitalised COVID-19: SPRINTER Phase III Study

Background Despite the availability of vaccines and therapies, patients are being hospitalised with COVID-19. Interferon-β is a naturally-occurring protein that stimulates host immune responses against most viruses, including SARS-CoV-2. SNG001 is a recombinant interferon-β1a formulation delivered to the lungs via nebuliser. SPRINTER assessed the efficacy and safety of SNG001 in adults hospitalised due to COVID-19 who required oxygen via nasal prongs or mask. Methods Patients were randomised double-blind to SNG001 (N=309) or placebo (N=314) once-daily for 14 days plus standard of care (SoC). The primary objective was to evaluate recovery after administration of SNG001 versus placebo, in terms of times to hospital discharge and recovery to no limitation of activity. Key secondary endpoints were: progression to severe disease or death;progression to intubation or death;and death. Results Median time to hospital discharge was 7.0 and 8.0 days with SNG001 and placebo, respectively (hazard ratio 1.06 [95%CI 0.89, 1.27];p=0.51);time to recovery was 25.0 days in both groups (1.02 [0.81, 1.28];p=0.89). There were no significant SNG001–placebo differences for the key secondary endpoints, with a 25.7% relative risk reduction in progression to severe disease or death (10.7% and 14.4%, respectively;odds ratio 0.71 [0.44, 1.15];p=0.161). Serious adverse events were reported by 12.6% and 18.2% patients with SNG001 and placebo, respectively. Conclusions Although the primary objective of the study was not met, SNG001 had a favourable safety profile, and the key secondary endpoints analysis suggested that SNG001 may have prevented progression to severe disease. Study registration number: ISRCTN85436698

Tuberculosis and COVID-19 co-infection in Serbia: Pandemic challenge in a low-burden country

Introduction COVID-19 and tuberculosis (TB) represent global threats to the public health system. The impact of COVID-19 on TB results in a reduction in the number of notified TB cases, delayed diagnosis and treatment, and increased case fatality and mortality rates. The aim of the study was to analyze the TB/COVID-19 co-infected cohort in Serbia as a low-burden country and compare it to the global TB/COVID-19 cohort. Methods A retrospective analysis was done on 53 TB and COVID-19 co-infected patients treated in COVID hospital “Batajnica” in Belgrade and Special Hospital for Pulmonary Diseases “Ozren” Sokobanja in the period from 6 March 2020 to 1 April 2022. A comparative analysis with the global cohort published recently was also performed. Results TB/COVID-19 cohort in Serbia included significantly fewer migrants and diabetes cases, but more cases with chronic respiratory diseases compared to the global. Descriptive analysis of TB cases in the Serbian TB/COVID-19 cohort showed fewer cases diagnosed with sputum smear and Gene Xpert/HAIN, fewer EPTB and mono-resistant cases, and more cases diagnosed with solid culture, unilateral pulmonary infiltrate (with bilateral cavity lesions), and bilateral pulmonary infiltrate (no cavities) compared to TB/COVID-19 cases worldwide. Nasal congestion and fever were more common COVID-19 symptoms in the global cohort. Radiology was more commonly used for the diagnosis of COVID-19 in Serbia. Typical bilateral ground opacities were less common among Serbian patients. Serbian patients spent fewer days in the hospital and achieved a higher PCR conversion rate and TB treatment success rate. Conclusion The Serbian TB/COVID-19 cohort achieved a higher treatment success rate compared to the global cohort. Encouraging vaccination against SARS-CoV-2 for people with a current or past TB disease, as well as rapid diagnosis and targeted treatment of TB in highly specialized pulmonology institutions, presents key points to avoid excessive morbidity and mortality.

Coronavirus disease 2019 in patients with chronic immune thrombocytopenia on thrombopoietin receptor agonists: new perspectives and old challenges.

There are limited data on the impact of severe acute respiratory syndrome corona virus 2 infection in patients previously diagnosed with primary immune thrombocytopenia (ITP) on thrombopoietin receptor agonist therapy (TPO-RA). Seven chronic ITP patients who had contracted COVID-19 and had been treated with TPO-RA are included in the study. Demographic, ITP treatment and comorbidities data were collected retrospectively from patients' medical records. Data regarding clinical course of COVID-19 were collected prospectively. During the infection, all patients had platelet count higher than average, and platelet count peak was mainly observed on day 7. For that reason, therapy modification was required. However, platelet count increment was transient in most ITP patients. One patient developed pulmonary embolism despite the use of therapeutic dose of anticoagulants. One patient died of respiratory failure whereas another developed rebound thrombocytopenia after the infection and consequential intracerebral hemorrhage. Careful platelet count monitoring and therapy management are needed in chronic ITP patients on TPO-RAs with COVID-19.

Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey.

BACKGROUND: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. METHODS: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. RESULTS: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. CONCLUSIONS: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.

Successful Immunomodulatory Treatment of COVID-19 in a Patient With Severe ACTH-Dependent Cushing's Syndrome: A Case Report and Review of Literature.

Introduction: Patients with Cushing's syndrome (CS) represent a highly sensitive group during corona virus disease 2019 (COVID-19) pandemic. The effect of multiple comorbidities and immune system supression make the clinical picture complicated and treatment challenging. Case report: A 70-year-old female was admitted to a covid hospital with a severe form of COVID-19 pneumonia that required oxygen supplementation. Prior to her admission to the hospital she was diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS, and the treatment of hypercortisolism had not been started yet. Since the patient's condition was quickly deteriorating, and with presumend immmune system supression due to CS, we decided on treatement with intraveonus immunoglobulins (IVIg) that enabled quick onset of immunomodulatory effect. All comorbidities were treated with standard of care. The patient's condition quickly stabilized with no direct side effects of a given treatment. Conclusion: Treatment of COVID-19 in patients with CS faces many challenges due to the complexity of comorbidity effects, immunosupression and potential interactions of available medications both for treatment of COVID-19 and CS. So far, there are no guidelines for treatment of COVID-19 in patients with active CS. It is our opinion that immunomodulating therapies like IVIg might be an effective and safe treatment modality in this particularly fragile group of patients.

Fatal invasive candidiasis in COVID-19 patient with severe bleeding and extensively drug-resistant Klebsiella enterobacter.

INTRODUCTION: Multi-organ dysfunction caused by thromboembolic complications may complicate the course of SARS-CoV-2 infection. Most patients require anticoagulant therapy which predisposes them to the development of hemorrhagic syndrome. In critically ill COVID-19 patients secondary infections due to opportunistic pathogens are associated with a high mortality rate. CASE REPORT: Herein, we present a COVID-19 patient with severe hemorrhage at unusual sites complicated with invasive candidiasis and an extensively drug-resistant (XDR) strain of Klebsiella enterobacter. CONCLUSIONS: Clinicians should be aware of the possibility for invasive fungal infections in severely ill patients with SARS-CoV-2 infection due to pre-existing conditions, risk factors, and COVID-19 associated pathological mechanisms. Management of invasive candidiasis is challenging because of the high prevalence of comorbidities, risk of toxicities, and drug interactions.