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Cytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers. We studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU. Patients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin. IL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Over the past decades, it has become increasingly evident that sleep disturbance contributes to inflammation-mediated disease, including depression, mainly through activation of the innate immune system and to an increased risk of infections., Methods: A comprehensive literature search was performed in PubMed to identify relevant research findings in the field of immunity, inflammation and infections, with a focus on translational research findings from the past 5 years., Results: Physiological sleep is characterized by a dynamic interplay between the immune system and sleep architecture, marked by increased innate immunity and T helper 1 (Th1) -mediated inflammation in the early phase, transitioning to a T helper 2 (Th2) response dominating in late sleep. Chronic sleep disturbances are associated with enhanced inflammation and an elevated risk of infections, while other inflammatory diseases may also be affected. Conversely, inflammation in response to infection can also disrupt sleep patterns and architecture. This narrative review summarizes current data on the complex relationships between sleep, immunity, inflammation and infections, while highlighting translational aspects. The bidirectional nature of these interactions are addressed within specific conditions such as sleep apnea, HIV, and other infections. Furthermore, technical developments with the potential to accelerate our understanding of these interactions are identified, including advances in wearable devices, artificial intelligence, and omics technology. By integrating these tools, novel biomarkers and therapeutic targets for sleep-related immune dysregulation may be identified., Conclusion: The review underscores the importance of understanding and addressing immune imbalance related to sleep disturbances to improve disease outcomes., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objectives: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients., Methods: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients., Results: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence)., Conclusions: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hanna-Riikka Kreivi is a consultant for Pfizer and Roche and received lecture honoraria from Pfizer. Tiina Mattila is an advisory board member for GSK and received lecture honoraria from AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, and Orion. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients., Methods: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records., Results: Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy., Conclusion: Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy., (© 2024. The Author(s).)

Background: In Turku, Finland, we introduced a home oxygen treatment and app-based monitoring program for hospitalized COVID-19 patients to facilitate an early discharge during the Omicron wave. In this case series we explore the clinical parameters of patients enrolled in the program and evaluate the cost-benefit and safety issues of the program., Methods: Hospitalized COVID-19 patients with marked hypoxemia but otherwise in stable condition were screened from Turku City Hospital and Turku University Hospital by treating doctors for eligibility in the program. Peripheral oxygen saturation of > 92% and breathing frequency < 30/min in rest with oxygen supplementation were among the criteria. All patients actively participating in the program between 10 th of January 2022 and 30 th of September 2022 were included in this case series. Clinical data of hospitalization and monitoring were analysed, and cost-benefit evaluation was based on the number of saved hospitalization days., Results: Nineteen COVID-19 patients were included in this case series and recruited from three different hospital departments in the Turku city region, South-West Finland. All patients were male, the median age was 59 years and the median duration of hospitalization before enrolment in the program was 6 days (range 3-20 days). The median duration of home oxygen treatment was 13 days (range 3-72 days) and the median duration of home monitoring was 18 days (range 7-41 days). A total of 210,5 hospital days were prevented, resulting in savings of €144,490 of healthcare expenditure (on average 9 days and €7,605 per patient). No major safety issues were reported during the program., Conclusions: In our case series, home oxygen treatment combined with home monitoring was safe and economically beneficial. Application based monitoring could be considered in other post-acute pulmonary conditions to reduce hospitalization and healthcare costs., (© 2023. The Author(s).)

Background: Sleep apnea is associated with chronic comorbidities and acute complications. Existing data suggest that sleep apnea may predispose to an increased risk and severity of respiratory tract infections., Methods: We investigated the incidence of lower respiratory tract infections in the first and second year before and after diagnosis of sleep apnea in a Finnish nationwide, population-based, retrospective case-control study based on linking data from the national health care registers for primary and secondary care from 2015-2019. Controls were matched for age, sex, hospital district, and multimorbidity status. We furthermore analysed the independent effect of comorbidities and other patient characteristics on the risk of lower respiratory tract infections, and their recurrence., Results: Sleep apnea patients had a higher incidence of lower respiratory tract infections than their matched controls within one year before (hazard ratio 1.35, 95% confidence interval 1.16-1.57) and one year after (hazard ratio1.39, 95% confidence interval1.22-1.58) diagnosis of sleep apnea. However, we found no difference in the incidence of lower respiratory tract infections within the second year before or after diagnosis of sleep apnea in comparison with matched controls. In sleep apnea, history of lower respiratory tract infection prior to sleep apnea, multimorbidity, COPD, asthma, and age greater than 65 years increased the risk of incident and recurrent lower respiratory tract infections., Conclusions: Sleep apnea patients are at increased risk of being diagnosed with a lower respiratory tract infection within but not beyond one year before and after diagnosis of sleep apnea. Among sleep apnea patients, chronic comorbidities had a significant impact on the risk of lower respiratory tract infections and their recurrence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: World Health Organization recommends tuberculosis (TB) preventive treatment for risk groups such as patients preparing for organ transplantation. Pretransplant screening or treatment of latent TB infection has not been routine practice in Finland., Methods: In this nationwide registry study, we assessed the risk of TB among kidney transplant recipients compared to the general population. TB cases were identified by data linkage of the national infectious disease and the national transplant registries between 1995 and 2019. Standardized incidence ratios were calculated with adjustment for age, sex, and annual TB dynamics., Results: A total of 4101 kidney transplants in 3900 recipients with a follow-up of 37 652 patient-years were included. Eighteen TB cases were detected. Patients diagnosed with TB were older (median age 64 y, interquartile range 56-66) at transplantation than those without TB (median 51 y, interquartile range 41-60, P < 0.001). The standardized incidence ratio of TB was 6.9 among kidney transplant recipients compared to general population during the whole study period 1995-2019 but decreased from 12.5 in 1995-2007 to 3.2 in 2008-2019. The standardized incidence ratio was 44.2 during the first year after transplantation. Significant differences in 5-y graft losses were not detected between TB patients and those without TB., Conclusions: The standardized incidence ratio of TB in kidney transplant recipients has decreased over the years, but these patients remain at risk of TB, especially during the first posttransplant year. Cost-benefit analysis is required to address feasibility of latent TB infection screening among transplant candidates in countries with low incidence of TB., Competing Interests: The other authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: In this retrospective cohort study, we explored the correlation of blood human myxovirus resistance protein A (MxA) level with severity of disease in hospitalized COVID-19 patients., Methods: All 304 patients admitted for COVID-19 in our hospital until 30th of April 2021 were included in this study. MxA was measured from peripheral blood samples in 268 cases. Patients were divided into groups based on their level of MxA on admission. We studied baseline characteristics and severity of disease on admission based on clinical parameters and inflammatory biomarker levels in each group. Severity of disease during hospitalization was determined by the applied level of respiratory support, by the usage of corticosteroids and by the duration of hospitalization., Results: Higher MxA levels on admission were associated with a shorter duration of symptoms before admission, and with more severe disease. Adjusted Odds Ratios for any respiratory support were 9.92 (95%CI 2.11-46.58; p = 0.004) in patients with MxA between 400 μg/L and 799 μg/L (p = 0.004) and 20.08 (95%CI 4.51-89.44; p < 0.001) in patients with MxA ≥ 800 μg/L in comparison with patients with initial MxA < 400 μg/L. The usage of corticosteroids was significantly higher in the high-MxA group (77%) in comparison with the intermediate-MxA group (62%, p = 0.013) and low-MxA group (47%, p < 0.001)., Conclusions: Higher initial levels of MxA were associated with more severe COVID-19. MxA may be a helpful additional biomarker to predict the severity of the disease., (© 2022. The Author(s).)

Objectives: Severe COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage., Methods: Patients hospitalized with COVID-19, hypoxemia, and at least two of four markedly elevated markers of inflammation (interleukin-6, C-reactive protein, ferritin, and/or D-dimer) were randomized for tocilizumab (TCZ) plus standard of care (SoC) or SoC alone. The primary endpoint was clinical status at day 28 assessed using a seven-category ordinal scale, and the secondary endpoints included intensive care unit admission, respiratory support, and duration of hospital admission., Results: Clinical status at day 28 was significantly better in patients who received TCZ in addition to SoC compared with those who received SoC alone (p = 0.037). By then, 93% of patients who received TCZ (n = 53 of 57) and 86% of control patients (n = 25 of 29) had been discharged from the hospital. In addition, 47% of TCZ patients (n = 27 of 57) and 24% of control patients (n = 7 of 29) had resumed normal daily activities. The median length of hospitalization was 9 days (interquartile range, 7-12) in the TCZ group and 12 days (interquartile range, 9-15) in the control group (p = 0.014)., Discussion: In patients hospitalized with COVID-19, hypoxemia, and elevated inflammation markers, administration of TCZ in addition to SoC was associated with significantly better clinical recovery by day 28 and a shorter hospitalization compared with SoC alone., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)