Search

This study investigates the prevalence and evaluates the prognostic implications of acute kidney injury (AKI) in COVID-19 patients, with a novel emphasis on the evaluation of serum uromodulin (sUmod) as a potential kidney-specific biomarker. A cohort of hospitalised COVID-19 patients (n = 378) was examined for AKI using standard criteria. In addition to traditional urinary biomarkers, sUmod levels were analysed. Univariable and multivariable regression models were employed to evaluate the association of sUmod and AKI and in-hospital mortality. Levels of sUmod were significantly lower in patients with CKD (91.8 ± 60.7 ng/ml) compared to patients with normal kidney function (204.7 ± 91.7 ng/ml; p < 0.001). 151 patients (40.0%) presented with AKI at the time of hospital admission or developed an AKI during hospitalization. 116 patients (76.8%) had an AKI already at the time of hospital admission. COVID-19 patients with AKI had significantly lower levels of sUmod compared to patients without AKI during hospitalisation (124.8 ± 79.5 ng/ml) vs 214.6 ± 92.3 ng/ml; p < 0.001). The in-hospital mortality rate in this cohort of COVID-19 patients was 15.3%. Patients with AKI had a higher probability for in-hospital death (OR 5.6, CI 1.76 to 17.881, p = 0.004). Patients who died during hospital stay, had significantly lower sUmod levels (129.14 ± 89.56 ng/ml) compared to patients surviving hospitalisation (187.71 ± 96,64 ng/ml; p < 0.001). AKI is frequently associated with COVID-19 in hospitalized patients. Serum uromodulin may emerge as a promising biomarker for AKI in COVID-19 patients. Further research is warranted to explore its clinical application and refine risk stratification in this patient population., (© 2024. The Author(s).)

Background: Metagenomic next-generation sequencing (mNGS) of circulating cell-free DNA from plasma is a hypothesis-independent broadband diagnostic method for identification of potential pathogens. So far, it has only been investigated in special risk populations (e.g. patients with neutropenic fever)., Purpose: To investigate the extent to which mNGS (DISQVER® platform) can be used in routine clinical practice., Methods: We collected whole blood specimens for mNGS testing, blood cultures (BC), and pathogen-specific PCR diagnostics. Clinical data and pathogen diagnostics were retrospectively reviewed by an infectious disease expert panel regarding the adjustment of anti-infective therapy., Results: In 55 selected patients (median age 53 years, 67% male) with heterogeneous diagnoses, a total of 66 different microorganisms and viruses were detected using mNGS (51% viruses, 38% bacteria, 8% fungi, 3% parasites). The overall positivity rate of mNGS was 53% (29/55). Fifty-two out of 66 (79%) potential pathogens detected by mNGS were found in patients with primary or secondary immunodeficiency. The concordance rates of BC and pathogen-specific PCR diagnostics with mNGS testing were 14% (4/28) and 36% (10/28), respectively (p < 0.001). An additional bacterial pathogen (Streptococcus agalactiae) could only be detected by BC. Therapeutic consequences regarding anti-infective therapy were drawn from 23 pathogens (35% of detections), with 18 of these detections occurring in patients with immunodeficiency., Conclusions: We conclude that mNGS is a useful diagnostic tool, but should only be performed selectively in addition to routine diagnostics of infectious diseases. The limited number of patients and the retrospective study design do not allow any further conclusions., (© 2024. The Author(s).)

Reduced lymphocyte counts in peripheral blood are one of the most common observations in acute phases of viral infections. Although many studies have already examined the impact of immune (dys)regulation during SARS-CoV-2 infection, there are still uncertainties about the long-term consequences for lymphocyte homeostasis. Furthermore, as persistent cellular aberrations have been described following other viral infections, patients with "Post-COVID-19 Condition" (PCC) may present similarly. In order to investigate cellular changes in the adaptive immune system, we performed a retrospective analysis of flow cytometric data from lymphocyte subpopulations in 106 patients with confirmed SARS-CoV-2 infection who received medical care at our institution. The patients were divided into three groups according to the follow-up date; laboratory analyses of COVID-19 patients were compared with 28 unexposed healthy controls. Regarding B lymphocyte subsets, levels of IgA + CD27+, IgG + CD27+, IgM + CD27- and switched B cells were significantly reduced at the last follow-up compared to unexposed healthy controls (UHC). Of the 106 COVID-19 patients, 56 were clinically classified as featuring PCC. Significant differences between PCC and COVID-19 convalescents compared to UHC were observed in T helper cells and class-switched B cells. However, we did not detect specific or long-lasting immune cellular changes in PCC compared to the non-post-COVID-19 condition.

Background: Infection-associated secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life-threatening hyperinflammatory condition caused by various infectious diseases. Malaria has rarely been described as trigger. The aim of this study is to collect data on frequency, clinical spectrum, and outcome of sHLH induced by malaria., Methods: We collected case numbers on malaria and malaria-associated sHLH from specialized centers in Germany from 2015 to 2022. In addition, we conducted a literature search on published cases of malaria-associated sHLH and systematically analyzed the literature regarding clinical and diagnostic criteria., Results: We obtained data from 13 centers treating 1461 malaria cases with different Plasmodium species, of which 5 patients (0.34%) also were diagnosed with sHLH. The literature search revealed detailed case reports from further 51 patients and case series comprising the description of further 24 patients with malaria-associated sHLH. Most cases (48/80; 60%) were reported from Asia. The median time interval between onset of malaria symptoms and hospital admission was 7 days. Severe complications of sHLH were documented in 36% (20/56) of patients, including two patients with multiple organ failure in our case series. Only 41% (23/56) of patients received specific treatment for sHLH, nevertheless the mortality rate (CFR) of 5% is lower compared to the CFR reported for sHLH triggered by other infectious diseases (e.g., 25% in sHLH due to EBV infection)., Conclusion: Malaria-associated sHLH appears to have a comparatively good prognosis but may still represent an underdiagnosed and potentially fatal complication of malaria, especially in resource-poor settings., (© 2023. The Author(s).)

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: To ensure the fastest and earliest possible treatment, the German Federal Ministry of Health (BMG) initiated central procurement and nationwide distribution of new drugs against COVID-19. A single centre was used for a retrospective temporal analysis of this procedure., Methods: A descriptive analysis of hospitalization and treatment of COVID-19 patients with drugs centrally procured by the BMG at St. Georg Hospital, Leipzig, Germany, for the period from 1 March 2020 to 28 February 2023 was employed considering the approval status, evolving guidelines and recommendations of medical societies., Results: In total, 3,412 patients ≥18 years (54.9% men) with PCR-confirmed SARS-CoV-2 infection were admitted. The mean age was 64 years during the reporting period and 66.1/70.6 years during the first and second COVID-19 waves, respectively. 964 patients (28.2%) received COVID-19 therapy with drugs procured centrally by the BMG. Remdesivir was the most commonly used (63%). SARS-CoV-2 neutralizing monoclonal antibodies represented 23% of the therapies. Peroral antivirals (nirmatrelvir/ritonavir and molnupiravir) were used in 14% of COVID-19 patients, with molnupiravir being insignificant (five prescriptions)., Conclusions: Specific therapeutic approaches were mainly based on antiviral therapy in the early phase of COVID-19 to prevent severe disease progression in vulnerable patient groups. Most drugs had not been approved at the time of central procurement; therefore, prescriptions were given on a case-by-case basis after careful risk-benefit assessments. All available neutralizing monoclonal SARS-CoV-2 antibodies lost efficacy during the pandemic due to different circulating immune escape variants. Remdesivir and nirmatrelvir/ritonavir remained effective therapies in the early phase of COVID-19., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 Marx et al.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: The benefits of antiviral treatment with remdesivir in hospitalized patients with COVID-19 remain controversial. Clinical analyses are needed to demonstrate which patient populations are most likely to benefit., Methods: In a retrospective monocentric analysis, patients with COVID-19 treated between July 1, 2020 and June 30, 2021 at Hospital St. Georg, Leipzig, Germany were evaluated. The primary endpoint was time to clinical improvement, and the secondary endpoint was 28-day mortality. Propensity score matching was used for the endpoint analysis., Results: A total of 839 patients were fully evaluated, 68% of whom received specific COVID-19 drug therapy. Remdesivir was used in 31.3% of the patients, corticosteroids in 61.7%, and monoclonal antibodies in 2.3%. While dexamethasone administration was the most common therapeutic approach during the second pandemic wave, combination therapy with remdesivir and corticosteroids predominated during the third wave. Cox regression analysis revealed that combination therapy was not associated with faster clinical improvement (median: 13 days in both matched groups, HR 0.97 [95% CI 0.77-1.21], P = 0.762). By contrast, 28-day mortality was significantly lower in the corticosteroid-remdesivir group (14.8% versus 22.2% in the corticosteroid group, HR 0.60 [95% CI 0.39-0.95], P = 0.03) in the low-care setting. This effect was also demonstrated in a subgroup analysis of patients with remdesivir monotherapy (n = 44) versus standard of care (SOC)., Conclusion: In COVID-19 patients with only mild disease (low-flow oxygen therapy and treatment in a normal ward) who received corticosteroids and/or remdesivir in addition to SOC, early administration of remdesivir was associated with a measurable survival benefit., (© 2022. The Author(s).)

Background: The currently used SARS-CoV-2 mRNA vaccines have proven to induce a strong and protective immune response. However, functional relevance of vaccine-generated antibodies and their temporal progression are still poorly understood. Thus, the central aim of this study is to gain a better understanding of systemic and mucosal humoral immune response after mRNA vaccination with BNT162b2., Methods: We compared antibody production against the S1 subunit and the RBD of the SARS-CoV-2 spike protein in sera of BNT162b2 vaccinees, heterologous ChAdOx1-S/BNT162b2 vaccinees and COVID-19 patients. We monitored the neutralizing humoral response against SARS-CoV-2 wildtype strain and three VOCs over a period of up to eight months after second and after a subsequent third vaccination., Results: In comparison to COVID-19 patients, vaccinees showed higher or similar amounts of S1- and RBD-binding antibodies but similar or lower virus neutralizing titers. Antibodies peaked two weeks after the second dose, followed by a decrease three and eight months later. Neutralizing antibodies (nAbs) poorly correlated with S1-IgG levels but strongly with RBD-IgGAM titers. After second vaccination we observed a reduced vaccine-induced neutralizing capacity against VOCs, especially against the Omicron variant. Compared to the nAb levels after the second vaccination, the neutralizing capacity against wildtype strain and VOCs was significantly enhanced after third vaccination. In saliva samples, relevant levels of RBD antibodies were detected in convalescent samples but not in vaccinees., Conclusions: Our data demonstrate that BNT162b2 vaccinated individuals generate relevant nAbs titers, which begin to decrease within three months after immunization and show lower neutralizing potential against VOCs as compared to the wildtype strain. Large proportion of vaccine-induced S1-IgG might be non-neutralizing whereas RBD-IgGAM appears to be a good surrogate marker to estimate nAb levels. A third vaccination increases the nAb response. Furthermore, the systemic vaccine does not seem to elicit readily detectable mucosal immunity., Competing Interests: The authors have declared that no competing interests exist.

Background: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker., Methods: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country., Findings: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6-77·1%) for mortality (threshold 0·47) and 67·4% (64·4-70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5-95% percentile interval 0·730-1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04)., Interpretation: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs., Funding: German Federal Ministry of Health., Competing Interests: Declaration of interests HM is the co-founder and co-owner of Mosaiques-Diagnostiques (Hannover, Germany). JS and JR are employees of Mosaiques-Diagnostics. HDR received consulting fees and honoraria for presentations from Alexion, AstraZeneca, and Bristol-Myers-Squibb. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Monitoring the humoral protective immune response and its durability after SARS-CoV-2 infections is essential for risk assessment of reinfections, the improvement of diagnostic methods and the evaluation of vaccine trials. We have analyzed neutralizing antibodies and IgG responses specific to different antigens, including the inactivated whole-virion of SARS-CoV-2, the spike subunit 1 protein and its receptor binding domain, as well as the nucleocapsid protein. We show the dynamic developments of the responses from the early convalescent stages up to 9 months post symptoms onset in follow-up samples from 57 COVID-19 patients with varying clinical severity. By correlating antibody signals to neutralizing titres, valid diagnostic markers for the estimation of neutralizing protection could be identified.

Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called "cytokine storm", with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19.

Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID-19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR-confirmed COVID-19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6-8 and 66 at WHO stages 1-3 COVID-19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha-1-antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID-19. The clinical corollary is that COVID-19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha-1-antitripsin, may represent a valid and effective therapeutic approach in COVID-19, targeting improvement of endothelial integrity., (© 2021 Wiley-VCH GmbH.)

Background: COVID-19 prediction models based on clinical characteristics, routine biochemistry and imaging, have been developed, but little is known on proteomic markers reflecting the molecular pathophysiology of disease progression., Methods: The multicentre (six European study sites) Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection Study (Crit-COV-U) is recruiting consecutive patients (≥ 18 years) with PCR-confirmed SARS-CoV-2 infection. A urinary proteomic biomarker (COV50) developed by capillary-electrophoresis-mass spectrometry (CE-MS) technology, comprising 50 sequenced peptides and identifying the parental proteins, was evaluated in 228 patients (derivation cohort) with replication in 99 patients (validation cohort). Death and progression along the World Health Organization (WHO) Clinical Progression Scale were assessed up to 21 days after the initial PCR test. Statistical methods included logistic regression, receiver operating curve (ROC) analysis and comparison of the area under the curve (AUC)., Findings: In the derivation cohort, 23 patients died, and 48 developed worse WHO scores. The odds ratios (OR) for death per 1 standard deviation (SD) increment in COV50 were 3·52 (95% CI, 2·02-6·13, p  <0·0001) unadjusted and 2·73 (1·25-5·95, p = 0·012) adjusted for sex, age, baseline WHO score, body mass index (BMI) and comorbidities. For WHO scale progression, the corresponding OR were 2·63 (1·80-3·85, p< 0·0001) and 3·38 (1·85-6·17, p< 0·0001), respectively. The area under the curve (AUC) for COV50 as a continuously distributed variable was 0·80 (0·72-0·88) for mortality and 0·74 (0·66-0·81) for worsening WHO score. The optimised COV50 thresholds for mortality and worsening WHO score were 0·47 and 0·04 with sensitivity/specificity of 87·0 (74·6%) and 77·1 (63·9%), respectively. On top of covariates, COV50 improved the AUC, albeit borderline for death, from 0·78 to 0·82 ( p = 0·11) and 0·84 ( p = 0·052) for mortality and from 0·68 to 0·78 ( p = 0·0097) and 0·75 ( p = 0·021) for worsening WHO score. The validation cohort findings were confirmatory., Interpretation: This first CRIT-COV-U report proves the concept that urinary proteomic profiling generates biomarkers indicating adverse COVID-19 outcomes, even at an early disease stage, including WHO stages 1-3. These findings need to be consolidated in an upcoming final dataset., Funding: The German Federal Ministry of Health funded the study., Competing Interests: AW, BC, BN, HvdL, AN, JB, AM, MM, ACT, BP, KR, CL, RW, SK, ED, JS report payment for study inclusion from the Federal Ministry of Health (Germany) during the conduct of the study; MS reports Scientific Research Activity from Robert Bosch Stiftung during the conduct of the study, grants for clinical trials from Green Cross Wellbeing Co. Ltd. And Gilead Sciences Inc. and grants for research activity from Robert Bosch GmbH, consulting fees as reviewer for Research Impact Fund Hongkong and EU Horizon 2020, honoraria for lectures from CED Service GmbH and ALL Akademie, supporting for meetings from CED Service GmbH and ALL Akademie, participation on advisory board (European PGx Advisory Board) from Agena Bioscience GmbH and other financial interests (Editor) for Phrmacogenetics and Genomics, Drug Research and Genome Medicine; JM, JS and JR are past (JM) or current employees of Mosaiques-Diagnostics, Hanover, Germany, HM is a co-funder and co-owner of Mosaiques-Diagnostics., (© 2021 The Author(s).)

Competing Interests: Declaration of Competing Interest The authors report no declarations of interest.

A 43-year-old Armenian patient was diagnosed with salmonella infection and thrombotic microangiopathy (TMA). The clinical course was benign with resolution of all laboratory alterations after antibiotic treatment. Constantly deficient ADAMTS13 activity without ADAMTS13 inhibitors and evidence of homozygosity for a rare complex ADAMTS13 allele led to the diagnosis of congenital thrombotic thrombocytopenic purpura (cTTP). Half-life of ADAMTS13 after plasma infusion was calculated (27,6h) and double blinded plasma infusion as well as ergometric exercise with and without prior plasma infusion undertaken to investigate suspected smoldering TTP activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wendt, Kalbitz, Otto, Falter, Beige, Rossmann and Lämmle.)

Background: Serological severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays differ in the target antigen specificity, e.g. of antibodies directed against the viral spike or the nucleocapsid protein, and in the spectrum of detected immunoglobulins. The aim of the study was to evaluate the performance of two different routinely used immunoassays in hospitalized and outpatient COVID-19 cases., Methods: The test characteristics of commercially available spike1 protein-based serological assays (Euroimmun, EI-assays), determining IgA or IgG and nucleocapsid-based assays (Virotech, VT-assays) determining IgA, IgM or IgG were compared in 139 controls and 116 hospitalized and outpatient COVID-19 cases., Results: Hospitalized COVID-19 patients (n = 51; 115 samples) showed significantly higher concentrations of antibodies against SARS-CoV-2 and differed from outpatient cases (n = 65) by higher age, higher disease severity scores and earlier follow up blood sampling. Sensitivity of the two IgG assays was comparable in hospitalized patients tested ≥ 14 days (EI-assay: 88%, CI 95% 67.6-99.9; VT-assay: 96%, CI 95% 77.7-99.8). In outpatient COVID-19 cases sensitivity was significantly lower in the VT-assay (86.2%, CI 95% 74.8-93.1) compared with the EI-assay (98.5%, CI 95% 90.6-99.9). Assays for IgA and IgM demonstrated a lack of specificity or sensitivity., Conclusions: Our results indicate that SARS-CoV-2 serological assays may need to be optimized to produce reliable results in outpatient COVID-19 cases who are low or even asymptomatic. Assays for IgA and IgM have limited diagnostic performance and do not prove an additional value for population-based screening approaches., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

We investigated potential transmissions of a symptomatic SARS-CoV-2-positive physician in a tertiary-care hospital who worked for 15 cumulative hours without wearing a face mask. No in-hospital transmissions occurred, despite 254 contacts among patients and healthcare workers. In conclusion, exposed hospital staff continued work, accompanied by close clinical and virologic monitoring.

SARS-CoV-2 infection results in a mild-to-moderate disease course in most patients, allowing outpatient self-care and quarantine. However, in approx. 10% of cases a two- or three-phasic critical disease course with starting from day 7 to 10 is observed. To facilitate and plan outpatient care, biomarkers prognosing such worsening at an early stage appear of outmost importance. In this accelerated article, we report on the identification of urinary peptides significantly associated with SARS-CoV-2 infection, and the development of a multi-marker urinary peptide based test, COVID20, that may enable prognosis of critical and fatal outcomes in COVID-19 patients. COVID20 is composed of 20 endogenous peptides mainly derived from various collagen chains that enable differentiating moderate or severe disease from critical state or death with 83% sensitivity at 100% specificity. Based on the performance in this pilot study, testing in a prospective study on 1000 patients has been initiated. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Background: To examine the all-cause mortality and uveal melanoma specific mortality among newly diagnosed uveal melanoma patients after five years. Furthermore, we assess of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma. Therefore, we assess the performance of an individual prediction model of survival from uveal melanoma., Methods: A cohort of 459 patients aged 45 to 79 years with newly diagnosed uveal melanoma was recruited between 2002 and 2004 from the Division of Ophthalmology, University of Essen, Germany. Survival probabilities were estimated by Kaplan-Meier survival analysis. The clinical and histopathological characteristics were obtained from medical records. Iris colour and childbearing history were assessed at baseline by a computer-assisted telephone interview. We used crude and multivariable Cox proportional hazards regression to estimate unadjusted and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (95%CIs) with respect to death from uveal melanoma and death from all causes. We used the Cox model to estimate adjusted probabilities of primary events. For computing Harrell's C statistics, we used a Cox model including the prognostics factors gender, age at diagnosis, ciliary body involvement, largest basal tumour diameter, and iris colour., Results: The 5-year uveal melanoma-specific survival probability was 82.9% (95% CI: 79.1-86.3). Main prognostic factors for the death of uveal melanoma were ciliary body involvement (HR: 1.7 (95% CI:1.0-2.8)), largest basal tumour diameter >15 mm HR: 7.0 (95% CI: 3.5-13.9), light iris colour (HR: 2.3 (95% CI: 0.9-5.8), having children (HR: 0.6 (95% CI: 0.2 - 1.7)), and gender (HR: 0.7 (95% CI: 0.4-1.1)). The value of the bootstrap-corrected C statistics was 0.76 (95% CI: 0.74-0.77)., Conclusion: Beyond the established prognostic factors, light iris colour also appears to be a prognostic factor for death from uveal melanoma.