| 1. |
- Ahlstrand, Erik, 1974-, et al.
(author)
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Visual scoring of chest CT at hospital admission predicts hospitalization time and intensive care admission in Covid-19
- 2021
-
In: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 53:8, s. 622-632
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Journal article (peer-reviewed)abstract
- BACKGROUND: Chest CT is prognostic in Covid-19 but there is a lack of consensus on how to report the CT findings. A chest CT scoring system, ÖCoS, was implemented in clinical routine on 1 April 2020, in Örebro Region, Sweden. The ÖCoS-severity score measures the extent of lung involvement. The objective of the study was to evaluate the ÖCoS scores as predictors of the clinical course of Covid-19.METHODS: Population based study including data from all hospitalized patients with Covid-19 in Örebro Region during March to July 2020. We evaluated the correlations between CT scores at the time of admission to hospital and intensive care in relation to hospital and intensive care length of stay (LoS), intensive care admission and death. C-reactive protein and lymphocyte count were included as covariates in multivariate regression analyses.RESULTS: In 381 included patients, the ÖCoS-severity score at admission closely correlated to hospital length of stay, and intensive care admission or death. At admission to intensive care, the ÖCoS-severity score correlated with intensive care length of stay. The ÖCoS-severity score was superior to basic inflammatory biomarkers in predicting clinical outcomes.CONCLUSION: Chest CT visual scoring at admission to hospital predicted the clinical course of Covid-19 pneumonia.
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| 2. |
- Ingberg, Edvin, 1988-, et al.
(author)
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RT-PCR cycle threshold value in combination with visual scoring of chest computed tomography at hospital admission predicts outcome in COVID-19
- 2022
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In: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 54:6, s. 431-440
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Journal article (peer-reviewed)abstract
- BACKGROUND: COVID-19 has a most variable prognosis. Several risk factors for an unfavourable outcome have been identified including extensive lung involvement on chest CT and high viral load estimated by RT-PCR cycle threshold (Ct) values. We investigated Ct value for outcome prediction, relation between Ct value and extent of lung involvement on chest CT and the combination of Ct value and chest CT lung involvement to predict outcome in COVID-19.METHODS: Population-based retrospective study on all patients (n = 286) hospitalised for COVID-19 in Örebro Region, Sweden, between 1 March and 31 August 2020. Nasopharyngeal samples and chest CT at hospital admission were evaluated in relation to outcome of COVID-19.RESULTS: Both Ct value and chest CT lung involvement were independently associated with risk for ICU admission or death. Lung involvement was superior as a single parameter, but addition of Ct value increased the prediction performance. Ct value was especially useful to identify patients with high risk for severe disease despite limited lung involvement.CONCLUSIONS: The addition of RT-PCR Ct value to the assessment of lung involvement on chest CT adds valuable prognostic information in COVID-19. We believe that this information can be used to support clinical decision-making when managing COVID-19 patients.
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| 3. |
- Nestor, David, 1992-, et al.
(author)
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Early prediction of blood stream infection in a prospectively collected cohort
- 2021
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Blood stream infection (BSI) and sepsis are serious clinical conditions and identification of the disease-causing pathogen is important for patient management. The RISE (Rapid Identification of SEpsis) study was carried out to collect a cohort allowing high-quality studies on different aspects of BSI and sepsis. The aim of this study was to identify patients at high risk for BSI who might benefit most from new, faster, etiological testing using neutrophil to lymphocyte count ratio (NLCR) and Shapiro score.METHODS: Adult patients (≥ 18 years) presenting at the emergency department (ED) with suspected BSI were prospectively included between 2014 and 2016 at Örebro University Hospital. Besides extra blood sampling, all study patients were treated according to ED routines. Electronic patient charts were retrospectively reviewed. A modified Shapiro score (MSS) and NLCR were extracted and compiled. Continuous score variables were analysed with area under receiver operator characteristics curves (AUC) to evaluate the ability of BSI prediction.RESULTS: The final cohort consisted of 484 patients where 84 (17%) had positive blood culture judged clinically significant. At optimal cut-offs, MSS (≥3 points) and NLCR (> 12) showed equal ability to predict BSI in the whole cohort (AUC 0.71/0.74; sensitivity 69%/67%; specificity 64%/68% respectively) and in a subgroup of 155 patients fulfilling Sepsis-3 criteria (AUC 0.71/0.66; sensitivity 81%/65%; specificity 46%/57% respectively). In BSI cases only predicted by NLCR> 12 the abundance of Gram-negative to Gram-positive pathogens (n = 13 to n = 4) differed significantly from those only predicted by MSS ≥3 p (n = 7 to n = 12 respectively) (p < 0.05).CONCLUSIONS: MSS and NLCR predicted BSI in the RISE cohort with similar cut-offs as shown in previous studies. Combining the MSS and NLCR did not increase the predictive performance. Differences in BSI prediction between MSS and NLCR regarding etiology need further evaluation.
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| 4. |
- Ahmad, Irma, et al.
(author)
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High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19
- 2023
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In: Frontiers in Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
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Journal article (peer-reviewed)abstract
- BACKGROUND: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae.METHODS: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression.RESULTS: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+.CONCLUSION: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.
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| 5. |
- Akhtar, Zubair, et al.
(author)
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Undiagnosed SARS-CoV-2 infection and outcome in patients with acute MI and no COVID-19 symptoms
- 2021
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In: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 8:1
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Journal article (peer-reviewed)abstract
- OBJECTIVE: We aimed to determine the prevalence and outcome of occult infection with SARS-CoV-2 and influenza in patients presenting with myocardial infarction (MI) without COVID-19 symptoms.METHODS: We conducted an observational study from 28 June to 11 August 2020, enrolling patients admitted to the National Institute of Cardiovascular Disease Hospital, Dhaka, Bangladesh, with ST-segment elevation MI (STEMI) or non-ST-segment elevation MI who did not meet WHO criteria for suspected COVID-19. Samples were collected by nasopharyngeal swab to test for SARS-CoV-2 and influenza virus by real-time reverse transcriptase PCR. We followed up patients at 3 months (13 weeks) postadmission to record adverse cardiovascular outcomes: all-cause death, new MI, heart failure and new percutaneous coronary intervention or stent thrombosis. Survival analysis was performed using the Kaplan-Meier method.RESULTS: We enrolled 280 patients with MI, 79% male, mean age 54.5±11.8 years, 140 of whom were diagnosed with STEMI. We found 36 (13%) to be infected with SARS-CoV-2 and 1 with influenza. There was no significant difference between mortality rate observed among SARS-CoV-2 infected patients compared with non-infected (5 (14%) vs 26 (11%); p=0.564). A numerically shorter median time to a recurrent cardiovascular event was recorded among SARS-CoV-2 infected compared with non-infected patients (21 days, IQR: 8-46 vs 27 days, IQR: 7-44; p=0.378).CONCLUSION: We found a substantial rate of occult SARS-CoV-2 infection in the studied cohort, suggesting SARS-CoV-2 may precipitate MI. Asymptomatic patients with COVID-19 admitted with MI may contribute to disease transmission and warrants widespread testing of hospital admissions.
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| 6. |
- Björsell, Tove, et al.
(author)
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Risk factors for impaired respiratory function post COVID-19 : A prospective cohort study of nonhospitalized and hospitalized patients
- 2023
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In: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Inc.. - 0954-6820 .- 1365-2796. ; 293:5, s. 600-614
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Journal article (peer-reviewed)abstract
- BACKGROUND: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3-6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness.METHODS: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO ), was performed 3-6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed.RESULTS: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO , versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO . A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO .CONCLUSION: Reduced DLCO was the major respiratory impairment 3-6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.
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| 7. |
- Cajander, Sara, 1980-, et al.
(author)
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Covid-19
- 2022. - 2
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In: Infektionsmedicin. - : Studentlitteratur AB. - 9789144153308 ; , s. 43-50
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Book chapter (peer-reviewed)
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| 8. |
- Cajander, Sara, 1980-
(author)
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Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Monocytic human leukocyte antigen-D related (mHLA-DR) expression determined by flow cytometry has been suggested as a biomarker of sepsisinduced immunosuppression.In order to facilitate use of HLA-DR in clinical practice, a quantitative real-time PCR technique measuring HLA-DR at the transcription level was developed and evalutated. Levels of HLA-DR mRNA correlated to mHLADR expression and were robustly measured, with high reproducibility, during the course of infection. Dynamics of mHLA-DR expression was studied during the first weeks of bloodstream infection (BSI) and was found to be dependent on the bacterial etiology of BSI. Moreover, mHLA-DR was shown to be inversely related to markers of inflammation. In patients with unfavourable outcome, sustained high C-reactive protein level and high neutrophil count were demonstrated along with low mHLA-DR expression and low lymphocyte count. This supports the theory of sustained inflammation in sepsis-induced immunosuppression. The association between mHLA-DR and bacterial etiology may be linked to the clinical trajectory via differences in ability to cause intractable infection. Staphylococcus aureus was the dominating etiology among cases with unfavourable outcome. With focus on patients with S. aureus BSI, those with complicated S. aureus BSI were found to have lower HLA-DR mRNA expression during the first week than those with uncomplicated S. aureus BSI. If these results can be confirmed in a larger cohort, HLA-DR measurement could possibly become an additional tool for early identification of patients who require further investigation to clear infectious foci and achieve source control.In conclusion, PCR-based measurement of HLA-DR is a promising method for measurements of the immune state in BSI, but needs further evaluation in the intensive care unit setting to define the predictive and prognostic value for deleterious immunosuppression. The etiology of infection should be taken into consideration in future studies of translational immunology in sepsis.
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| 9. |
- Cajander, Sara, 1980-, et al.
(author)
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Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection
- 2018
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:2
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Journal article (peer-reviewed)abstract
- OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti-inflammatory responses are key components, but knowledge is lacking on the association between bacterial etiology and development of dysregulated responses with sustained immunosuppression. The aim of this study was to evaluate how the immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with bacterial etiology and markers of inflammation during the clinical trajectory of bloodstream infection (BSI).METHODS: Ninety-one adults, predominantly non-ICU patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other species (n = 19) were prospectively included, and sampled on admission (day 0) and on days 1-2, 3, 7±1, 14±2, and 28±4.RESULTS: The dynamics of mHLA-DR, measured by flow cytometry, differed significantly between etiology groups (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and they demonstrated sustained C-reactive protein elevation, neutrophilia, lymphocytopenia, and loss of mHLA-DR.CONCLUSIONS: Dynamics of mHLA-DR varied according to the bacterial etiology of infection, with delayed recovery in patients with S. aureus BSI. Patients with negative outcome showed sustained CRP elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting the theory of a dysregulated host response with persistent inflammation and immunosuppression in late stages of deleterious sepsis.
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| 10. |
- Cajander, Sara, 1980-, et al.
(author)
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HLA-DRA and CD74 on intensive care unit admission related to outcome in sepsis
- 2018
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In: Critical Care. - : BioMed Central. - 1466-609X .- 1364-8535. ; 22:Suppl. 1
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Journal article (peer-reviewed)abstract
- Introduction: mRNA expressions of the major histocompatibility complex class II-related genes HLA-DRA and CD74 have been found to be promising markers for sepsis-induced immunosuppression. In the present study we aimed to study how expression of HLA-DRA and CD74 on intensive care unit (ICU) admission were related to death and/or secondary infections in patients with sepsis.Methods: During a full year adult patients admitted to the ICU of Karolinska University Hospital Huddinge were consecutively subjected to blood sampling within 1 hour from ICU admission. Patients treated with antibiotic therapy were eligible for inclusion. The plausibility of infection (definite, probable, possible, none) was determined based on the Centers for Diseases Control (CDC) criteria. Patients with sepsis (definite/probable/possible infection and a SOFA score increase of >=2) were screened for death within 60 days and secondary infections 48 h to 60 days after ICU admission, using the CDC criteria. HLA-DRA and CD74 mRNA expressions were determined by reverse transcription quantitative PCR.Results: Among 579 ICU admissions, a blood sample for RNA analysis was collected in 551 cases. Two hundred fifty-seven patients met the inclusion criteria and provided written informed consent. Sepsis was noted in 134 patients. The sepsis patients experienced death in 36 cases (27%), secondary infection in 32 cases (24%), and death and/or secondary infection in 60 cases (45%). Table 1 shows the results of HLA-DRA and CD74 expression related to death and secondary infections.Conclusions: The mRNA expression of HLA-DRA on ICU admission was significantly decreased in patients with sepsis who died or contracted secondary infections within 60 days. CD74 expression was not significantly decreased in patients with negative outcome.
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| 11. |
- Cajander, Sara, 1980-, et al.
(author)
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Mb Osler: ökad risk för infektioner och livshotande komplikationer : Fyra fall av invasiv infektionssjukdom under samma tidsperiod beskrivs
- 2012
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In: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 109:37, s. 1613-1615
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Journal article (peer-reviewed)abstract
- Mb Osler är internationellt mer känd under namnen heredi-tary hemorrhagic telangiectasia (HHT) eller Osler–Weber–Rendu syndrome. Sjukdomen beror på en nedärvd genetisk defekt, där den muterade genen påverkar TGF-superfamiljens signalering i kärlendotel. Detta leder till telangiektasier och ibland större arteriovenösa missbildningar [1]. Eftersom kärl-missbildningarna kan uppstå i olika organ varierar symtom-bilden mellan olika familjer och individer. En till två tredjede-lar av de drabbade söker någon gång medicinsk hjälp på grund av komplikationer till sjukdomen [2]. De vanligaste kliniska uttrycken är recidiverande näsblöd-ningar och järnbristanemi. Incidensen varierar geografiskt och finns rapporterad från 1/2351 till 1/39216 [3]. Diagnosen ställs med hjälp av de sk Curaçao-kriterierna [4] (Fakta 1). Hos en del patienter leder sjukdomen till svåra organkompli-kationer, och på senare tid har ökad risk för infektioner upp-märksammats. Vi beskriver fyra patienter med diagnosen Mb Osler som vårdades på grund av allvarlig infektionssjukdom under sam-ma tidsperiod.
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| 12. |
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| 13. |
- Cajander, Sara, 1980-, et al.
(author)
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Preliminary results in quantitation of HLA-DRA by real-time PCR : a promising approach to identify immunosuppression in sepsis
- 2013
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In: Critical Care. - London, United Kingdom : BioMed Central. - 1364-8535 .- 1466-609X. ; 17:5
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Journal article (peer-reviewed)abstract
- Introduction: Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections. However, traditional monitoring of mHLA-DR by flow cytometry has disadvantages due to specific laboratory requirements. An mRNA-based HLA-DR monitoring by polymerase chain reaction (PCR) would improve the clinical usage and facilitate conduction of large multicenter studies. In this study, we evaluated an mRNA-based HLA-DR monitoring by quantitative real-time PCR (qRT-PCR) as an alternative method to traditional flow cytometry.Methods: Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n = 30).Results: A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.Conclusions: Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.
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| 14. |
- Cajander, Sara, 1980-, et al.
(author)
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Profiling the dysregulated immune response in sepsis : overcoming challenges to achieve the goal of precision medicine
- 2024
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In: The Lancet Respiratory Medicine. - : Elsevier. - 2213-2600 .- 2213-2619. ; 12:4, s. 305-322
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Research review (peer-reviewed)abstract
- Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice. In this Review, we provide an overview of the current state of immune profiling in sepsis, including its use, current challenges, and opportunities for progress. We highlight the important role of immunological biomarkers in facilitating predictive enrichment in current and future treatment scenarios. We propose that multiple immune and non-immune-related parameters, including clinical and microbiological data, be integrated into diagnostic and predictive combitypes, with the aid of machine learning and artificial intelligence techniques. These combitypes could form the basis of workable algorithms to guide clinical decisions that make precision medicine in sepsis a reality and improve patient outcomes.
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| 15. |
- Cajander, Sara, 1980-, et al.
(author)
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Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis
- 2016
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In: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 11:5
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Journal article (peer-reviewed)abstract
- Introduction: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).Aims: The aims of this study were: 1. to validate the robustness of qRT-PCR measurement of HLA-DRA- and CIITA-mRNA expression, in terms of reproducibility; and 2. to see if changes in expression of these genes reflect changes in mHLA-DR expression during the course of severe and non-severe bacteraemic sepsis.Methods and Findings: Blood samples were collected from 60 patients with bacteraemic sepsis on up to five occasions during Days 1-28 after hospital admission. We found the reproducibility of the qRT-PCR method to be high by demonstrating low threshold variations (<0.11 standard deviation (SD)) of the qRT-PCR system, low intra-assay variation of Ct-values within triplicates (≤0.15 SD) and low inter-assay variations (12%) of the calculated target gene ratios. Our results also revealed dynamic HLA-DRA expression patterns during the course of sepsis that reflected those of mHLA-DR measured by FCM. Furthermore, HLA-DRA and mHLA-DR recovery slopes in patients with non-severe sepsis differed from those in patients with severe sepsis, shown by mixed model for repeated measurements (p<0.05). However, during the first seven days of sepsis, PCR-measurements showed a higher magnitude of difference between the two sepsis groups. Mean differences (95% CI) between severe sepsis (n = 20) and non-severe sepsis (n = 40) were; on day 1-2, HLA-DRA 0.40 (0.28-0.59) p<0.001, CIITA 0.48 (0.32-0.72) p = 0.005, mHLA-DR 0.63 (0.45-1.00) p = 0.04, day 7 HLA-DRA 0.59 (0.46-0.77) p<0.001, CIITA 0.56 (0.41-0.76) p<0.001, mHLA-DR 0.81 (0.66-1.00) p = 0.28.Conclusion: We conclude that qRT-PCR measurement of HLA-DRA expression is robust, and that this method appears to be preferable to FCM in identifying patients with severe sepsis that may benefit from immunostimulation.
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| 16. |
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| 17. |
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| 18. |
- Gunst, Jesper D., et al.
(author)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Journal article (peer-reviewed)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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| 19. |
- Gylfe, Åsa, et al.
(author)
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Melioidos : en viktig diagnos vid svår sjukdom efter utlandsresa
- 2017
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In: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 114
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Journal article (peer-reviewed)abstract
- Melioidosis, an important diagnosis in the severely ill traveler Melioidosis is a common tropical infection in Southeast Asia and is caused by the highly pathogenic soil bacterium Burkholderia pseudomallei. Diagnosis and treatment is often challenging due to variations in clinical presentation, limited antibiotic susceptibility and high risk of recurring infection. In this report, three cases with different clinical presentations are described.
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| 20. |
- Hammarsten, Ola, et al.
(author)
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Clinical measurement of cellular DNA damage hypersensitivity in patients with DNA repair defects
- 2022
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In: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes. Six patients with variants in the DNA repair genes PRKDC (two siblings), DCLRE1C (two siblings), NBN, and MSH6 were included. Here, we used the cell division assay (CDA) and the gamma-H2AX assay, which were both developed and clinically validated by us, to measure patient cell hypersensitivity in response to ionizing radiation, mitomycin C, cytarabine and doxorubicin. Results: Radiation hypersensitivity was detected in the two patients with variants in the PRKDC gene (p < 0.0001 for both at 3.5 Gy), and the two patients with DCLRE1C variants (p < 0.0001 at 3.5 Gy for sibling 1 and p < 0.0001 at 1 Gy for sibling 2). The cells from the patients with the PRKDC variant were also deficient in removing gamma-H2AX (p < 0.001). The cells from the patient with variants in the NBN gene were hypersensitive to mitomycin C (p = 0.0008) and deficient in both induction and removal of gamma-H2AX in response to radiation. Conclusions: The combination of the CDA and the gamma-H2AX assay is useful in investigating the significance of unknown variants in some DNA repair genes.
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| 21. |
- Hellgren, Fredrika, et al.
(author)
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Modulation of innate immune response to mRNA vaccination after SARS-CoV-2 infection or sequential vaccination in humans
- 2024
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In: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708. ; 9:9
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Journal article (peer-reviewed)abstract
- mRNA vaccines are likely to become widely used for the prevention of infectious diseases in the future. Nevertheless, a notable gap exists in mechanistic data, particularly concerning the potential effects of sequential mRNA immunization or preexisting immunity on the early innate immune response triggered by vaccination. In this study, healthy adults, with or without documented prior SARS-CoV-2 infection, were vaccinated with the BNT162b2/Comirnaty mRNA vaccine. Prior infection conferred significantly stronger induction of proinflammatory and type I IFN-related gene signatures, serum cytokines, and monocyte expansion after the prime vaccination. The response to the second vaccination further increased the magnitude of the early innate response in both study groups. The third vaccination did not further increase vaccine-induced inflammation. In vitro stimulation of PBMCs with TLR ligands showed no difference in cytokine responses between groups, or before or after prime vaccination, indicating absence of a trained immunity effect. We observed that levels of preexisting antigen-specific CD4 T cells, antibody, and memory B cells correlated with elements of the early innate response to the first vaccination. Our data thereby indicate that preexisting memory formed by infection may augment the innate immune activation induced by mRNA vaccines.
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| 22. |
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| 23. |
- Hellman, Urban, 1966-, et al.
(author)
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Presence of hyaluronan in lung alveoli in severe Covid-19 : an opening for new treatment options?
- 2020
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In: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 295:45, s. 15418-15422
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Journal article (peer-reviewed)abstract
- Severe corona virus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up for new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.
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| 24. |
- Lange, Anna, 1975-, et al.
(author)
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Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection
- 2019
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In: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 38:8, s. 1425-1434
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Journal article (peer-reviewed)abstract
- The severity of bloodstream infections (BSI) depends on pathogen, source, and host factors. Secretory leukocyte protease inhibitor (SLPI) counteracts tissue damage, balances inflammation, and is increased in pneumonia and sepsis. We aimed to evaluate whether SLPI production differs depending on etiology, disease severity, and sex in BSI and to correlate SLPI with markers of inflammation and immunosuppression. Of the adult patients with BSI, 109 were included and sampled repeatedly, from hospital admission through day 28. Controls (blood donors) were sampled twice. SLPI in plasma was measured with enzyme-linked immunosorbent assay (ELISA) technique. Streptococcus pneumoniae and Staphylococcus aureus etiology were associated with higher SLPI than Escherichia coli on days 1-2 and 3. On day 1-2, subjects with sepsis had higher SLPI concentrations than those with non-septic BSI. Pneumonia was associated with higher SLPI than a non-pulmonary source of infection. SLPI co-varied with inflammatory markers. SLPI concentrations did not differ with regard to sex in the full cohort, but men with pneumonia had higher SLPI than women on day 1-2. S. pneumoniae and S. aureus BSI were associated with higher SLPI, when compared to E. coli. Severity and pneumonia, as well as male sex in the pneumonia sub-cohort, were factors independently associated with higher SLPI.
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| 25. |
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