Clinical phenotype and outcome of persistent SARS-CoV-2 replication in immunocompromised hosts: a retrospective observational study in the Omicron era.

PURPOSE: This study aims to describe clinical, virological and radiological characteristics as well as treatment strategies and outcomes of immunocompromised patients with persistent SARS-CoV-2 replication. METHODS: We performed a retrospective cohort study of immunocompromised patients at the University Medical Center Freiburg between 01/2022 and 05/2023. Patients with substantial immunosuppression and persistent SARS-CoV-2 detection (Ct-value < 30 after 14 days) were included. RESULTS: 36 patients in our cohort reported mainly fever, dyspnoea or continuous cough. Viral load was significantly higher in concurrent samples taken from the lower respiratory tract (Ct-value = 26) than from the upper respiratory tract (Ct-value = 34). Time of detectable viral RNA after start of antiviral treatment was shorter in patients receiving two antivirals (median 15 days vs. 31 days with one antiviral agent). Short-course antiviral therapy (≤ 5 days) was less efficient in reduction of symptoms and viral load than prolonged therapy > 10 days. In 30% (8/27) of patients with repeated CT scans, we found the emergence of chronic pulmonary changes, which were more frequently in patients with B cell depletion (37%, 7/19) compared to patients with organ transplantation (12%, 2/17). CONCLUSION: Ongoing SARS-CoV-2 replication in the lower respiratory tract is a relevant differential diagnosis in patients with severe immunosuppression and continuous cough, fever or dyspnoea even if nasopharyngeal swabs test negative for SARS-CoV-2. Especially in B cell-depleted patients, this may lead to inflammatory or fibrotic-like pulmonary changes, which are partially reversible after inhibition of viral replication. Antiviral therapy seems to be most effective in combination and over a prolonged period of time of > 10 days. TRIAL REGISTRATION NUMBER: DRKS 00027299.

[Sarcoidosis and berylliosis]. / Sarkoidose und Berylliose.

Sarcoidosis and berylliosis (chronic beryllium disease, CBD) are granulomatous diseases and are phenocopies which cannot be differentiated based on the clinical presentation. Whereas for sarcoidosis the eliciting agent is unknown, for berylliosis an exposure to beryllium (mostly as occupational exposure) can be confirmed that therefore induces a sensitization against beryllium. The diagnosis is generally made in patients with a typical clinical presentation, the histological proof of a non-necrotizing granuloma and the exclusion of other diseases causing granulomas. In most cases, granulomas can be detected in the lungs and/or (intrathoracic) lymph nodes. The proof of sensitization to beryllium for the differential diagnosis can be performed with a so-called beryllium lymphocyte proliferation test in peripheral mononuclear blood cells or cells from a bronchoalveolar lavage. The objectives of treatment are avoidance of functional organ impairment and symptom control. Immunosuppressive therapy (initially mostly with corticosteroids) and supportive measures can prove beneficial; however, in many cases clinical observation can be sufficient because of stable disease or spontaneous resolution. In addition, further beryllium exposure must be avoided, which mostly necessitates a change of the workplace.

Successful treatment of extensive calcifications and acute pulmonary involvement in dermatomyositis with the Janus-Kinase inhibitor tofacitinib - A report of two cases.

INTRODUCTION: Dermatomyositis (DM) can be complicated by calcinosis and interstitial lung disease (ILD). Calcinosis can be severely debilitating or life-threatening and to date there is no treatment with proven efficacy. In DM type I interferon contributes to pathophysiology by inducing the expression of proinflammatory cytokines and the JAK-STAT (signal transducer and activator of transcription) pathway may be involved in the regulation of mitochondrial calcium store release, a process potentially important for calcification in DM. JAK-inhibition may therefore be an attractive therapy in DM complicated by calcifications. METHODS AND RESULTS: We report on the fast and persistent response of extensive and rapidly progressive DM-associated calcifications in two patients treated with the JAK-inhibitor tofacitinib. During the 28-week observation period in both patients no new calcifications formed and existing calcifications were either regressive or stable. Furthermore, concomitant life-threatening DM-associated ILD (acute fibrinous and organizing pneumonia; AFOP) in one patient rapidly responded to tofacitinib monotherapy. Both patients were able to taper concomitant glucocorticoids. Tofacitinib was well tolerated and safe. CONCLUSIONS: The results of our study support the role of JAK/STAT signaling in the development of calcinosis and ILD in DM. Tofacitinib may be an effective and safe treatment for calcinosis in DM and potentially for other connective tissue disease complicated by calcinosis.

Vaccination protects against acute respiratory distress syndrome (ARDS) in hospitalized patients with COVID-19.

This study aimed to analyze the effect of COVID-19 vaccination on the occurrence of ARDS in hospitalized COVID-19 patients. The study population of this retrospective, single-center cohort study consisted of hospitalized COVID-19 patients with known vaccination status and chest computed tomography imaging between July 2021 and February 2022. The impact of vaccination on ARDS in COVID-19 patients was assessed through logistic regression adjusting for demographic differences and confounding factors with statistical differences determined using confidence intervals and effect sizes. A total of 167 patients (69% male, average age 58 years, 95% CI [55; 60], 42% fully vaccinated) were included in the data analysis. Vaccinated COVID-19 patients had a reduced relative risk (RR) of developing ARDS (RR: 0.40, 95% CI [0.21; 0.62]). Consequently, non-vaccinated hospitalized patients had a 2.5-fold higher probability of developing ARDS. This risk reduction persisted after adjusting for several confounding variables (RR: 0.64, 95% CI [0.29; 0.94]) in multivariate analysis. The protective effect of COVID-19 vaccination increased with ARDS severity (RR: 0.61, 95% CI [0.37; 0.92]). Particularly, patients under 60 years old were at risk for ARDS onset and seemed to benefit from COVID-19 vaccination (RR: 0.51, 95% CI [0.20; 0.90]). COVID-19 vaccination showed to reduce the risk of ARDS occurrence in hospitalized COVID-19 patients, with a particularly strong effect in patients under 60 years old and those with more severe ARDS.

Cardioprotective effects of vaccination in hospitalized patients with COVID-19.

COVID-19 vaccination has been shown to prevent and reduce the severity of COVID-19 disease. The aim of this study was to explore the cardioprotective effect of COVID-19 vaccination in hospitalized COVID-19 patients. In this retrospective, single-center cohort study, we included hospitalized COVID-19 patients with confirmed vaccination status from July 2021 to February 2022. We assessed outcomes such as acute cardiac events and cardiac biomarker levels through clinical and laboratory data. Our analysis covered 167 patients (69% male, mean age 58 years, 42% being fully vaccinated). After adjustment for confounders, vaccinated hospitalized COVID-19 patients displayed a reduced relative risk for acute cardiac events (RR: 0.33, 95% CI [0.07; 0.75]) and showed diminished troponin T levels (Cohen's d: - 0.52, 95% CI [- 1.01; - 0.14]), compared to their non-vaccinated peers. Type 2 diabetes (OR: 2.99, 95% CI [1.22; 7.35]) and existing cardiac diseases (OR: 4.31, 95% CI [1.83; 10.74]) were identified as significant risk factors for the emergence of acute cardiac events. Our findings suggest that COVID-19 vaccination may confer both direct and indirect cardioprotective effects in hospitalized COVID-19 patients.

[Lesions of the prevascular mediastinum]. / Läsionen des prävaskulären Mediastinums.

CLINICAL/METHODOLOGICAL ISSUE: Mediastinal masses are a group of heterogenous lesions which may be a coincidental finding or present with symptoms. More than half of mediastinal lesions are located in the prevascular mediastinum. As these tumors are not often encountered in clinical routine, making a diagnosis with a high degree of confidence may seem challenging. STANDARD RADIOLOGICAL METHODS: The latest computed tomography (CT)-based classification of the mediastinal compartments by the International Thymic Malignancy Interest Group (ITMIG) moves away from earlier radiograph-based classification systems and helps to reliably classify tumors based on location, although in some cases the lesion can occupy more than one compartment. PERFORMANCE: Radiology plays an important role in the evaluation of anterior mediastinal lesions. Although in some cases imaging features alone allow a diagnosis to be made; in other cases knowledge of important radiological features and their analysis in the context of patient factors like age and duration of symptoms can help to narrow down the differential diagnosis, avoid unnecessary workup, and guide further steps. PRACTICAL RECOMMENDATIONS: Computed tomography (CT) is central for the characterization of mediastinal masses in clinical routine. In some situations, like in the case of thymic cysts or thymic hyperplasia, magnetic resonance imaging (MRI) can be used as a noninvasive problem-solving tool.

Pulmonary computed tomographic manifestations of COVID-19 in vaccinated and non-vaccinated patients.

This study aimed to analyze computed tomographic (CT) imaging features of vaccinated and non-vaccinated COVID-19 patients. The study population of this retrospective single-center cohort study consisted of hospitalized COVID-19 patients who received a chest CT at the study site between July 2021 and February 2022. Qualitative scoring systems (RSNA, CO-RADS, COV-RADS), imaging pattern analysis and semi-quantitative scoring of lung changes were assessed. 105 patients (70,47% male, 62.1 ± 16.79 years, 53.3% fully vaccinated) were included in the data analysis. A significant association between vaccination status and the presence of the crazy-paving pattern was observed in univariate analysis and persisted after step-wise adjustment for possible confounders in multivariate analysis (RR: 2.19, 95% CI: [1.23, 2.62], P = 0.024). Scoring systems for probability assessment of the presence of COVID-19 infection showed a significant correlation with the vaccination status in univariate analysis; however, the associations were attenuated after adjustment for virus variant and stage of infection. Semi-quantitative assessment of lung changes due to COVID-19 infection revealed no association with vaccination status. Non-vaccinated patients showed a two-fold higher probability of the crazy-paving pattern compared to vaccinated patients. COVID-19 variants could have a significant impact on the CT-graphic appearance of COVID-19.

Comparative study to assess efficacy and safety of brinzolamide1% and timolol0.5% fixed combination eye drops versus dorzolamide2% and timolol0.5% fixed combination eye drops in management of open-angle glaucoma.

Aim and Objective: To compare the efficacy and safety of brinzolamide1% and timolol0.5% fixed combination eye drops versus dorzolamide2% and timolol0.5% fixed combination eye drops in the treatment of primary open-angle glaucoma. Design: Prospective, randomized, comparative, interventional study. Setting: Tertiary eye care centre. Material and Method: The present study was a comparative study carried out on patients visiting OPD of Ophthalmology Department and diagnosed with primary open-angle glaucoma. Group 1 (n-30 BT) received brinzolamide1% and timolol0.5% fixed combination eye drops, and Group 2 (N-30 DT) patients received dorzolamide2% and timolol0.5% fixed combination eye drops. A complete ophthalmic examination was performed, including Goldmann applanation tonometry. IOP was measured twice daily (9 AM and 4 PM). The patients were evaluated at 2, 4, 8, and 12 weeks. IOP was measured at follow-up. Side effects and tolerability of both drugs were assessed, and patient preference for drugs was noted. Results: Mean reduction in morning IOP was significantly more in Group 1 than in Group 2 at 8 weeks and 12 weeks (p < 0.05). Mean reduction in evening IOP was significantly more in Group 1 than in Group 2 at all follow-ups (p < 0.05). Conclusion: Brinzolamide1% + timolol0.5% fixed drug combination is more preferred and effective in lowering IOP than dorzolamide2% + timolol0.5% fixed drug combination in patients of primary open-angle glaucoma.

Computed Tomographic Imaging Features of COVID-19 Pneumonia Caused by the Delta (B.1.617.2) and Omicron (B.1.1.529) Variant in a German Nested Cohort Pilot Study Group.

BACKGROUND: The aim of this study was to evaluate CT (computed tomography) imaging differences for the Delta and the Omicron variant in COVID-19 infection. METHODS: The study population was derived from a retrospective study cohort investigating chest CT imaging patterns in vaccinated and nonvaccinated COVID-19 patients. CT imaging patterns of COVID-19 infection were evaluated by qualitative and semiquantitative scoring systems, as well as imaging pattern analysis. RESULTS: A total of 60 patients (70.00% male, 62.53 ± 17.3 years, Delta: 43 patients, Omicron: 17 patients) were included. Qualitative scoring systems showed a significant correlation with virus variants; "typical appearance" and "very high" degrees of suspicion were detected more often in patients with Delta (RSNA: p = 0.003; CO-RADS: p = 0.002; COV-RADS: p = 0.001). Semiquantitative assessment of lung changes revealed a significant association with virus variants in univariate (Delta: 6.3 ± 3.5; Omicron: 3.12 ± 3.2; p = 0.002) and multivariate analysis. The vacuolar sign was significantly associated with the Delta variant (OR: 14.74, 95% CI: [2.32; 2094.7], p = 0.017). CONCLUSION: The Delta variant had significantly more extensive lung involvement and showed changes classified as "typical" more often than the Omicron variant, while the Omicron variant was more likely associated with CT findings such as "absence of pulmonary changes". A significant correlation between the Delta variant and the vacuolar sign was observed.

Abatacept Use Is Associated with Steroid Dose Reduction and Improvement in Fatigue and CD4-Dysregulation in CVID Patients with Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) represents a severe clinical manifestation of systemic immune dysregulation in patients with common variable immunodeficiency (CVID). Its treatment often requires systemic immunosuppression beyond corticosteroids. OBJECTIVE: To assess the safety and efficacy of abatacept in patients with CVID and ILD. METHODS: Ten patients with confirmed diagnosis of CVID and ILD were included in a single-center, prospective, open-label, nonrandomized trial. Abatacept was administered subcutaneously at a dose of 125 mg/wk for 12 months. RESULTS: Abatacept was a safe treatment for ILD in CVID except for 1 case of bronchopulmonary aspergillosis. One additional patient terminated the trial prematurely because of recurrent bronchitis. Five of 8 patients treated per protocol benefited from the treatment according to American Thoracic Society/European Respiratory Society criteria. The primary end point of the study was met because single breath diffusing capacity of the lung for carbon monoxide was stable (62.5%) or improved (37.5%) in all patients treated per protocol. Although nodules (71%) and ground-glass opacities (57%) improved in most patients, other computed tomography pathologies were less responsive. Quality of life improved in 87.5% and fatigue in 57% of patients. Abatacept treatment was associated with significant improvement in CD4 T-cell dysregulation, signified by a decrease in serum soluble IL-2 receptor levels and of proliferating Ki67+ CD4 T cells, and a recovery of total lymphocytes, CD4+ T cells, and naive CD4 T cells. CONCLUSIONS: Abatacept may represent a treatment option for CVID-associated ILD. This pilot study demonstrated a good safety profile, steroid-sparing effect, positive immune modulation, and overall positive treatment response especially in quality of life. Larger controlled studies are needed to confirm these findings.

Recommendations of the Thoracic Imaging Section of the German Radiological Society for clinical application of chest imaging and structured CT reporting in the COVID-19 pandemic. / Empfehlungen der AG Thoraxdiagnostik der Deutschen Röntgengesellschaft zur klinischen Anwendung der Thoraxbildgebung und strukturierten CT-Befundung bei COVID-19-Pandemie.

This information provided by the Thoracic Imaging Section of the German Radiological Society is intended to give physicians recommendations on the use of thoracic imaging procedures in the context of the current COVID-19 pandemic. It represents the consensus of the authors based on the previous scientific knowledge and is intended to provide guidance for unified, structured CT reporting if COVID-19 pneumonia is suspected. The recommendations presented correspond to state of knowledge at the time of print and will be updated according to the results of ongoing and future scientific studies. KEY POINTS:: · COVID-19. · chest imaging. · German Radiological Society. CITATION FORMAT: · Vogel-Claussen J, Ley-Zaporozhan J, Agarwal P et al. Recommendations of the Thoracic Imaging Section of the German Radiological Society for clinical application of chest imaging and structured CT reporting in the COVID-19 pandemic. Fortschr Röntgenstr 2020; DOI: 10.1055/a-1174-8378.

The clinicopathologic manifestations of Plasmodium vivax malaria in children: a growing menace.

CONTEXT: Today, India faces increasing morbidity and mortality due to malaria, which is a global health burden. Plasmodium vivax which was once considered to have a benign course, is now being increasingly associated with complicated malaria. Studies which have been done on the increasing virulence of P. Vivax in children, are exceptionally rare. AIMS: This study has addressed some of the hitherto unanswered questions, such as: This study has tried to explore the wide spectrum of severe illnesses which are associated with P.vivax malaria in children.Other co-morbid conditions, which include a co-infection with P.falciparum, have been excluded with great care, to assess the increased virulence of P. Vivax.The present study was focused on the paediatric population with a large sample size of 168 subjects. SETTINGS AND DESIGN: This was an observational retrospective analysis on the clinicopathologic manifestations of the paediatric cases which were admitted with severe malaria due to a mono-infection with Plasmodium vivax, in a tertiary-care centre in the national capital region, India. METHODS AND MATERIAL: The diagnosis of the mono-infection with P. Vivax malaria was established by making peripheral blood films (PBFs) and by doing rapid diagnostic tests. The severe forms of malaria were categorized as per the World Health Organization guidelines and the clinical and laboratory findings in these cases of complicated malaria were studied. STATISTICS: A descriptive statistical analysis was done by using the SPSS software and an Excel worksheet. RESULTS: This comprehensive study revealed a multisystem involvement. Abdominal manifestations were observed in 75(45.8%) cases (which included hepatosplenomegaly, hepatomegaly, splenomegaly and ascites) and hepatic dysfunction and jaundice were observed in 28(16.7%) cases. The haematological tests showed moderate to severe anaemia in 151(89.9%) cases and thrombocytopaenia in 138(82.1%) cases. Petechiae were noted in 45(26.8%) cases and a gross bleeding was noted in 9(5.3%) cases. The respiratory findings which included tachypnoea, pleural effusions and ARDS were observed in 22(13.1%) cases. Renal dysfunction was noted clinically in 20(11.9%) cases and biochemically in 16(9.5%) cases. Shock was observed in 7(4.1%) cases, cerebral malaria was observed in 10(5.9%) cases and hypoglycaemia was observed in 5(3%) cases. Multi-organ dysfunction was detected in 11(6.54%) cases. The complications were more severe in the younger children (0-5 years). CONCLUSIONS: A mono-infection with P. Vivax may lead to severe malaria and this increased virulence has resulted in the changing picture of P. Vivax malaria, leading to a spectrum of complications which are similar to those which are traditionally associated with P. Falciparum.