90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection.

Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its antiviral potential in SARS-CoV-2 infection remains largely unknown. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients at multiple levels. We quantified 90K protein concentrations in serum and PBMCs as well as LGALS3BP mRNA levels. Complementary, we analyzed two single cell RNA-sequencing datasets for expression of LGALS3BP in respiratory specimens and PBMCs from COVID-19 patients. Finally, we analyzed the potential of 90K to interfere with SARS-CoV-2 infection of HEK293T/ACE2, Calu-3 and Caco-2 cells using authentic virus. 90K protein serum concentrations were significantly elevated in COVID-19 patients compared to uninfected sex- and age-matched controls. Furthermore, PBMC-associated concentrations of 90K protein were overall reduced by SARS-CoV-2 infection in vivo, suggesting enhanced secretion into the extracellular space. Mining of published PBMC scRNA-seq datasets uncovered monocyte-specific induction of LGALS3BP mRNA expression in COVID-19 patients. In functional assays, neither 90K overexpression in susceptible cell lines nor exogenous addition of purified 90K consistently inhibited SARS-CoV-2 infection. Our data suggests that 90K/LGALS3BP contributes to the global type I IFN response during SARS-CoV-2 infection in vivo without displaying detectable antiviral properties in vitro.

Changes in emergency department utilisation in Germany before and during different phases of the COVID-19 pandemic, using data from a national surveillance system up to June 2021.

BACKGROUND: During the COVID-19 pandemic and associated public health and social measures, decreasing patient numbers have been described in various healthcare settings in Germany, including emergency care. This could be explained by changes in disease burden, e.g. due to contact restrictions, but could also be a result of changes in utilisation behaviour of the population. To better understand those dynamics, we analysed routine data from emergency departments to quantify changes in consultation numbers, age distribution, disease acuity and day and hour of the day during different phases of the COVID-19 pandemic. METHODS: We used interrupted time series analyses to estimate relative changes for consultation numbers of 20 emergency departments spread throughout Germany. For the pandemic period (16-03-2020 - 13-06-2021) four different phases of the COVID-19 pandemic were defined as interruption points, the pre-pandemic period (06-03-2017 - 09-03-2020) was used as the reference. RESULTS: The most pronounced decreases were visible in the first and second wave of the pandemic, with changes of - 30.0% (95%CI: - 32.2%; - 27.7%) and - 25.7% (95%CI: - 27.4%; - 23.9%) for overall consultations, respectively. The decrease was even stronger for the age group of 0-19 years, with - 39.4% in the first and - 35.0% in the second wave. Regarding acuity levels, consultations assessed as urgent, standard, and non-urgent showed the largest decrease, while the most severe cases showed the smallest decrease. CONCLUSIONS: The number of emergency department consultations decreased rapidly during the COVID-19 pandemic, without extensive variation in the distribution of patient characteristics. Smallest changes were observed for the most severe consultations and older age groups, which is especially reassuring regarding concerns of possible long-term complications due to patients avoiding urgent emergency care during the pandemic.

Changes of radiological examination volumes over the course of the COVID-19 pandemic: a comprehensive analysis of the different waves of infection.

OBJECTIVES: Data from radiological departments provide important information on overall quantities of medical care provided. With this study we used a comprehensive analysis of radiological examinations as a surrogate marker to quantify the effect of the different COVID-19 waves on medical care provided. METHODS: Radiological examination volumes during the different waves of infection were compared among each other as well as to time-matched control periods from pre-pandemic years using a locally weighted scatterplot smoothing as well as negative binominal regression models. RESULTS: A total of 1,321,119 radiological examinations were analyzed. Examination volumes were reduced by about 10% over the whole study period (IRR = 0.90; 95% CI 0.89-0.92), with a focus on acute medical care (0.84; 0.83-0.85) and outpatients (0.93: 0.90-0.97). When compared to wave 1, examination volumes were about 17% higher during wave 2 (1.17; 1.10-1.25), and 33% higher in wave 3 of the pandemic (1.33; 1.24-1.42). CONCLUSIONS: This study shows the severe effect of COVID-19 pandemic and related shutdown measures on overall provided medical care as measured by radiological examinations. When compared, the decrease of medical care was more pronounced in the earlier waves of the pandemic.

CT-Based Risk Stratification for Intensive Care Need and Survival in COVID-19 Patients-A Simple Solution.

We evaluated a simple semi-quantitative (SSQ) method for determining pulmonary involvement in computed tomography (CT) scans of COVID-19 patients. The extent of lung involvement in the first available CT was assessed with the SSQ method and subjectively. We identified risk factors for the need of invasive ventilation, intensive care unit (ICU) admission and for time to death after infection. Additionally, the diagnostic performance of both methods was evaluated. With the SSQ method, a 10% increase in the affected lung area was found to significantly increase the risk for need of ICU treatment with an odds ratio (OR) of 1.68 and for invasive ventilation with an OR of 1.35. Male sex, age, and pre-existing chronic lung disease were also associated with higher risks. A larger affected lung area was associated with a higher instantaneous risk of dying (hazard ratio (HR) of 1.11) independently of other risk factors. SSQ measurement was slightly superior to the subjective approach with an AUC of 73.5% for need of ICU treatment and 72.7% for invasive ventilation. SSQ assessment of the affected lung in the first available CT scans of COVID-19 patients may support early identification of those with higher risks for need of ICU treatment, invasive ventilation, or death.

Low SARS-CoV-2 seroprevalence but high perception of risk among healthcare workers at children's hospital before second pandemic wave in Germany.

BACKGROUND: Healthcare workers are considered a particularly high-risk group during the coronavirus disease 2019 (COVID-19) pandemic. Healthcare workers in paediatrics are a unique subgroup: they come into frequent contact with children, who often experience few or no symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, therefore, may transmit the disease to unprotected staff. In Germany, no studies exist evaluating the risk of COVID-19 to healthcare workers in paediatric institutions. METHODS: We tested the staff at a large children's hospital in Germany for immunoglobulin (Ig) G antibodies against the nucleocapsid protein of SARS-CoV-2 in a period between the first and second epidemic wave in Germany. We used a questionnaire to assess each individual's exposure risk and his/her own perception of having already been infected with SARS-CoV-2. RESULTS: We recruited 619 participants from all sectors, clinical and non-clinical, constituting 70% of the entire staff. The seroprevalence of SARS-CoV-2 antibodies was 0.325% (95% confidence interval 0.039-1.168). Self-perceived risk of a previous SARS-CoV-2 infection decreased with age (odds ratio, 0.81; 95% confidence interval, 0.70-0.93). Having experienced symptoms more than doubled the odds of a high self-perceived risk (odds ratio, 2.18; 95% confidence interval, 1.59-3.00). There was no significant difference in self-perceived risk between men and women. CONCLUSIONS: Seroprevalence was low among healthcare workers at a large children's hospital in Germany before the second epidemic wave, and it was far from a level that confers herd immunity. Self-perceived risk of infection is often overestimated.

Critical Illness and Systemic Inflammation Are Key Risk Factors of Severe Acute Kidney Injury in Patients With COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development. METHODS: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development. Descriptive statistics and explanatory multivariable Cox regression modeling with clinical parameters as time-varying covariates were used to identify risk factors of severe AKI. RESULTS: Severe AKI developed in 70 of 223 patients (31%) with COVID-19, of which 95.7% required kidney replacement therapy. Patients with severe AKI were older, predominantly male, had more comorbidities, and displayed excess mortality. Severe AKI occurred exclusively in intensive care unit patients, and 97.3% of the patients developing severe AKI had respiratory failure. Mechanical ventilation, vasopressor therapy, and inflammatory markers (serum procalcitonin levels and leucocyte count) were independent time-varying risk factors of severe AKI. Increasing inflammatory markers displayed a close temporal association with the development of severe AKI. Sensitivity analysis on risk factors of AKI stage 2 and 3 combined confirmed these findings. CONCLUSION: Severe AKI in COVID-19 was tightly coupled with critical illness and systemic inflammation and was not observed in milder disease courses. These findings suggest that traditional systemic AKI mechanisms rather than kidney-specific processes contribute to severe AKI in COVID-19.

Decreased Medical Care During the COVID-19 Pandemic - A Comprehensive Analysis of Radiological Examinations.

OBJECTIVES: As a cross-section discipline within the hospital infrastructure, radiological departments might be able to provide important information regarding the impact of the COVID-19 pandemic on healthcare. The goal of this study was to quantify changes in medical care during the first wave of the pandemic using radiological examinations as a comprehensive surrogate marker and to determine potential future workload. METHODS: A retrospective analysis of all radiological examinations during the first wave of the pandemic was performed. The number of examinations was compared to time-matched control periods. Furthermore, an in-depth analysis of radiological examinations attributed to various medical specialties was conducted and postponed examinations were extrapolated to calculate additional workload in the near future. RESULTS: A total of 596,760 examinations were analyzed. Overall case volumes decreased by an average of 41 % during the shutdown compared to the control period. The most affected radiological modalities were sonography (-54 %), X-ray (-47 %) followed by MRI (-42 %). The most affected medical specialty was trauma and orthopedics (-60 % case volume) followed by general surgery (-49 %). Examination numbers increased during the post-shutdown period leading to a predicted additional workload of up to 22 %. CONCLUSION: This study shows a marked decrease in radiological examinations in total and among several core medical specialties, indicating a significant reduction in medical care during the first COVID-19 shutdown. KEY POINTS: · Number of radiological examinations decreased by 41 % during the first wave of the COVID-19 pandemic.. · Several core medical specialties were heavily affected with a reduction of case volumes up to 60 %.. · When extrapolating postponed examinations to the near future, the overall workload for radiological departments might increase up to 22 %.. CITATION FORMAT: · Fleckenstein FN, Maleitzke T, Böning G et al. Decreased Medical Care During the COVID-19 Pandemic - A Comprehensive Analysis of Radiological Examinations. Fortschr Röntgenstr 2021; 193: 937 - 946.

Diagnostic Value of Initial Chest CT Findings for the Need of ICU Treatment/Intubation in Patients with COVID-19.

Computed tomography (CT) plays an important role in the diagnosis of COVID-19. The aim of this study was to evaluate a simple, semi-quantitative method that can be used for identifying patients in need of subsequent intensive care unit (ICU) treatment and intubation. We retrospectively analyzed the initial CT scans of 28 patients who tested positive for SARS-CoV-2 at our Level-I center. The extent of lung involvement on CT was classified both subjectively and with a simple semi-quantitative method measuring the affected area at three lung levels. Competing risks Cox regression was used to identify factors associated with the time to ICU admission and intubation. Their potential diagnostic ability was assessed with receiver operating characteristic (ROC)/area under the ROC curves (AUC) analysis. A 10% increase in the affected lung parenchyma area increased the instantaneous risk of intubation (hazard ratio (HR) = 2.00) and the instantaneous risk of ICU admission (HR 1.73). The semi-quantitative measurement outperformed the subjective assessment diagnostic ability (AUC = 85.6% for ICU treatment, 71.9% for intubation). This simple measurement of the involved lung area in initial CT scans of COVID-19 patients may allow early identification of patients in need of ICU treatment/intubation and thus help make optimal use of limited ICU/ventilation resources in hospitals.