The SARS-CoV-2 pandemic in Germany may represent the sum of a large number of local but independent epidemics each initiated by individuals aged 10-19 years, middle-aged males, or elderly individuals.

Many epidemiological aspects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemics, particularly those affecting children, are still sparsely elucidated. Data on the first pandemic phase during the year 2020 indicated that children might serve as a virus reservoir. We now analyzed data on more than 530 000 SARS-CoV-2 polymerase chain reaction (PCR) and 12 503 anti-SARS-CoV-2 antibody tests performed in the west of Germany until Week 4 of 2021. We show that children of at least 10 years of age may play a prominent role in the pandemic showing highest PCR-positive rates in the first (Weeks 28-35), second (Weeks 42-48), and third wave (Week 50 of 2020-Week 2 2021) of the second pandemic phase, although the waves were not mainly initiated by children. The waves' kinetics differed even in nearby cities. Low PCR-positive rates were confined to areas of lower population density. PCR-positive rates were higher among middle-aged males compared with women and among very old females compared with males. From Week 25, seroprevalence rates slowly increased to 50%, indicating ongoing virus activity. In conclusion, the SARS-CoV-2 pandemics is characterized by many local but interacting epidemics, initiated and driven by different social groups. Children may not be the main initiators of virus spreading but older children may significantly affect the course of the pandemic. High population density is associated with higher SARS-CoV-2 incidence.

Retarded decline of the share of SARS-CoV-2-positive children in North Rhine-Westphalia, Germany.

Knowledge on the mechanisms of viral spread, of time-related changes, and age-specific factors of severe acute respiratory syndrome coronavirus 2 infections is important to develop recommendations aimed at controlling the pandemic. In this context, longitudinal data on proportions of positive results in different age groups are rare. Data on total positive counts and on shares of positive counts deriving from a private (MVZ) and a University (RWTH) laboratory were analyzed retrospectively and compared with public data on total positive counts of the Robert Koch Institute (RKI). Data were covered for Weeks 9-24 of the year 2020 and all patient ages. Total positive counts were lower in children compared to adults. Proportions of children and adults tested positive were 3%-5% and 5%-7%, respectively. RKI and MVZ data showed similar time-related patterns. Patients of 20-60 years of age did account for the initial virus spread (maximum infection rates at Weeks 9-11). Thereafter, infection rates decreased in older patients whereas children did not show a comparable time-related decrease. Pediatric data generated in outpatient settings and hospitals differed markedly which should be considered in further studies. In summary, compared with adults children are less affected by severe acute respiratory syndrome coronavirus 2 infections and are unlikely to account for the initial viral spread. However, children show sustained viral activity and may serve as a viral reservoir.

Favorable COVID-19 course despite significant comorbidities in a ruxolitinib-treated patient with primary myelofibrosis.

COVID-19 carries a high risk of severe disease course, particularly in patients with comorbidities. Therapy of severe COVID-19 infection has relied on supportive intensive care measures. More specific approaches including drugs that limit the detrimental "cytokine storm", such as Janus-activated kinase (JAK) inhibitors, are being discussed. Here, we report a compelling case of a 55-yo patient with proven COVID-19 pneumonia, who was taking the JAK1/2 inhibitor ruxolitinib in-label for co-existing primary myelofibrosis for 15 months prior to coronavirus infection. The patient had significant comorbidities, including chronic kidney disease, arterial hypertension, and obesity, and our previous cohort suggested that he was thus at high risk for acute respiratory distress syndrome (ARDS) and death from COVID-19. Since abrupt discontinuation of ruxolitinib may cause fatal cytokine storm and ARDS, ruxolitinib treatment was continued and was well tolerated, and the patient´s condition remained stable, without the need for mechanical ventilation or vasopressors. The patient became negative for SARS-CoV-2 and was discharged home after 15 days. In conclusion, our report provides clinical evidence that ruxolitinib treatment is feasible and can be beneficial in patients with COVID-19 pneumonia, preventing cytokine storm and ARDS.

Universal Mass Vaccination Against Rotavirus: Indirect Effects on Rotavirus Infections in Neonates and Unvaccinated Young Infants Not Eligible for Vaccination.

BACKGROUND: Rotavirus (RV)-associated infections account for high numbers of hospitalizations in neonates and young infants. Universal mass vaccination (UMV) has been shown to prevent the burden of disease in vaccinated children. METHODS: The present study investigated the long-term effects of UMV on RV-associated hospitalizations in children with particular focus on neonates and young infants (≤42 days old) not eligible for vaccination. Ten years of Austrian surveillance data were compared, including 10 960 laboratory-confirmed RV cases before (prevaccination period [PreVP]) and after (postvaccination period [PostVP]) introduction of UMV. RESULTS: A postvaccination decrease in hospitalized community-acquired RV infections by 89.3% was seen in all age groups, including unvaccinated neonates and young infants. Of the latter, 27.6% had a nosocomial RV infection in PreVP, and 19.3% in PostVP. Overall, the proportion of nosocomial RV infections increased from 5.5% in PreVP to 13.0% in PostVP. Breakthrough infections, usually after incomplete RV vaccination, could be identified in 6.2% of patients. CONCLUSIONS: Unvaccinated neonates and infants ≤42 days old may indirectly benefit from UMV by reduction of RV infections. Breakthrough infections underline the importance of early and complete protection by the vaccine. In older patients, heightened awareness of nosocomial RV infections is warranted. Identification of RV reservoirs is also needed.

A simple clinical score to reduce unnecessary testing for Puumala hantavirus.

BACKGROUND: Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), an endemic form of transient acute renal injury (AKI). Serological testing is the mainstay of diagnosis. It was the aim of the present study to assist decision-making for serological testing by constructing a simple tool that predicts the likelihood of PUUV positivity. METHODS: We conducted a comparative cohort study of all PUUV-tested cases at Aachen University tertiary care center in Germany between mid-2013 and mid-2021. N = 293 qualified for inclusion; N = 30 had a positive test result and clinical NE; N = 263 were negative. Two predictive point scores, the Aachen PUUV Score (APS) 1 and 2, respectively, were derived with the aid of logistic regression and receiver operating characteristic (ROC) analysis by determining the presence of four admission parameters. For internal validation, the internal Monte Carlo method was applied. In addition, partial external validation was performed using an independent historic cohort of N = 41 positive cases of NE. RESULTS: APS1 is recommended for clinical use as it estimated the probability of PUUV positivity in the entire medical population tested. With a range from 0 to 6 points, it yielded an area under the curve of 0.94 by allotting 2 points each for fever or headache and 1 point each for AKI or LDH>300 U/L. A point sum of 0-2 safely predicted negativity for PUUV, as was confirmed in the NE validation cohort. CONCLUSION: Here, we present a novel, easy-to-use tool to guide the diagnostic management of suspected PUUV infection/NE and to safely avoid unnecessary serological testing, as indicated by point sum class 0-2. Since 67% of the cohort fell into this stratum, half of the testing should be avoidable in the future.

Failure to detect an association between aggressive periodontitis and the prevalence of herpesviruses.

BACKGROUND: Herpes simplex virus type 1 (HSV-1), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have been suspected to play a causal role in periodontitis pathogenesis. The aim of this study was to determine the prevalence of these viruses in subgingival plaque samples of Caucasian patients with generalized aggressive periodontitis compared to periodontally healthy controls. METHODS: A total of 65 patients with aggressive periodontitis and 65 unmatched controls from Germany were investigated in the study. Subgingival plaque samples were analysed for the presence of HSV-1, EBV and HCMV by quantitative real-time polymerase chain reaction assays. Viral antibody titres were determined quantitatively by immunosorbent assays. RESULTS: DNA of HSV-1 and HCMV were detected in 1.5% of the patients and controls, whereas EBV DNA was present in 10.8% and 13.9% respectively. Detection rates of serum IgG against HSV-1 (76.1% versus 73.9%), EBV (98.5% versus 96.9%), HCMV (47.7% versus 46.2%) and IgM levels against HSV-1 (6.2% versus 1.5%), EBV (0% versus 0%), HCMV (0% versus 1.5%) did not significantly differ between patients and controls. CONCLUSION: The data of our study do not suggest any contribution of HSV-1, EBV or HCMV to aggressive periodontitis in a German population. Ethnic and methodological aspects might have caused conflicting results of previous studies.

Humoral immune response to SARS-CoV-2 mRNA vaccines is associated with choice of vaccine and systemic adverse reactions.

Purpose: Although the fast development of safe and effective messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 has been a success, waning humoral immunity has led to the recommendation of booster immunization. However, knowledge of the humoral immune response to different booster strategies and the association with adverse reactions is limited. Materials and Methods: We investigated adverse reactions and anti-spike protein immunoglobulin G (IgG) concentrations among health care workers who received primary immunization with mRNA-1273 and booster immunization with mRNA-1273 or BNT162b2. Results: Adverse reactions were reported by 85.1% after the first dose, 94.7% after the second dose, 87.5% after a third dose of BNT162b2, and 86.0% after a third dose of mRNA-1273. They lasted for a median of 1.8, 2.0, 2.5, and 1.8 days, respectively; 6.4%, 43.6%, and 21.0% of the participants were unable to work after the first, second, and third vaccination, respectively, which should be considered when scheduling vaccinations among essential workers. Booster immunization induced a 13.75-fold (interquartile range, 9.30-24.47) increase of anti-spike protein IgG concentrations with significantly higher concentrations after homologous compared to heterologous vaccination. We found an association between fever, chills, and arthralgia after the second vaccination and anti-spike protein IgG concentrations indicating a linkage between adverse reactions, inflammation, and humoral immune response. Conclusion: Further investigations should focus on the possible advantages of homologous and heterologous booster vaccinations and their capability of stimulating memory B-cells. Additionally, understanding inflammatory processes induced by mRNA vaccines might help to improve reactogenicity while maintaining immunogenicity and efficacy.

Two at one blow: reemergence of tularemia in Upper Austria.

After field dressing a rabbit in the state of Upper Austria, Austria two members of a family were infected with tularemia in November 2010. The patients were a man in his forties and his father-in-law in his sixties. Tularemia is a rare disease in Austria. In the last 10 years between 2 and 8 cases have been reported annually. Of the total of 40 cases none was reported in the state of Upper Austria. Thus, this case report documents the reemergence of tularemia in Upper Austria.

Large inter-individual variability of cellular and humoral immunological responses to mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in health care workers.

PURPOSE: Studies on the immune responses to severe acute respiratory syndrome coronavirus 2 vaccines are necessary to evaluate the ongoing vaccination programs by correlating serological response data and clinical effectiveness data. We performed a longitudinal immunological profiling of health care workers vaccinated with mRNA-1273 (Moderna, Cambridge, MA, USA). Half of these vaccinees had experienced a mild coronavirus disease 2019 (COVID-19) infection in the spring of 2020 ("COVID-recovered" cohort), whereas the other half of the vaccinees had no previous COVID-19 infection ("COVID-naive" cohort). MATERIALS AND METHODS: Serum was drawn at multiple time points and subjected to assays measuring anti-Spike immunoglobulin G (IgG), avidity of anti-Spike IgG, avidity of anti-receptor binding domain (RBD) IgG, virus neutralizing activity, and interferon-γ release from stimulated lymphocytes. RESULTS: Between both cohorts and within each cohort, we found remarkable inter-individual differences regarding cellular and humoral immune responses to the Moderna mRNA-1273 vaccine. CONCLUSION: First, our study indicates that the success of mRNA-1273 vaccinations should be verified by serological assays in order to identify "low-responders" to vaccination. Second, the kinetics of anti-S IgG and neutralizing activity correlate well with clinical effectiveness data, thus explaining incipient protection against infection 2 weeks after the first dose of mRNA-1273 in COVID-naive vaccinees. Third, our IgG-avidity data indicate that this incipient protection is mediated by low-avidity anti-RBD IgG and low-avidity anti-S IgG.

Severity of adverse reactions is associated with T-cell response in mRNA-1273 vaccinated health care workers.

Knowledge about mRNA-1273 elicited T-cell response is limited. We investigated adverse reactions and interferon gamma release by specific T-cells among mRNA-1273 vaccinated health care workers. Seven to 13 weeks after complete vaccination low levels of specific T-cells were detected not correlating with antibody response. Severity of symptoms after first and number of symptoms after second immunization were associated with T-cell response. Assessment of T-cell response in addition to antibody response is crucial because even few specific T-cells could add to protection against infection. Investigation of mRNA-1273 induced inflammatory processes might help improve reactogenicity and immunogenicity.

Two novel SARS-CoV-2 surrogate virus neutralization assays are suitable for assessing successful immunization with mRNA-1273.

BACKGROUND: Due to large vaccination efforts with novel vaccines there is an increasing need for laboratory tests assessing successful immunizations with SARS-CoV-2 vaccines. Unfortunately classical neutralization assays are laborious, time-consuming and require an adequate biosafety level laboratory. Recently, convenient ELISA-based surrogate neutralization assays (sVNTs) for determination of neutralizing SARS-CoV-2 antibodies have been developed. STUDY DESIGN: Our study compares the two novel ELISA-based SARS-CoV-2 surrogate neutralization assays "cPass SARS-CoV-2 Surrogate Virus Neutralization Test Kit" (GenScript Biotech, USA) and the "TECO SARS-CoV-2 Neutralization Antibody Assay" (TECOmedical, Switzerland) using 93 sera drawn from health care workers (HCVs) 2-3 weeks following the second vaccination with mRNA-1273 and 40 control sera from the pre-SARS-CoV-2 era before 2019. RESULTS: We found a sensitivity of 100% and 91,4% and a specificity of 100% and 100% for the GenScript assay and the TECO assay, respectively. Both sVNTs show a high correlation with anti-S IgG. Moreover, both sVNTs correlate well with each other. CONCLUSIONS: Surrogate neutralization assays based on the RBD as bait feature a high specificity and sensitivity for identifying humoral neutralizing activity in individuals vaccinated with the spike-based vaccine mRNA-1273. Although these assays appear well-suited for confirming successful vaccinations with spike-based vaccines, additional studies should compare both assays regarding other purposes such as screening COVID-recovered patients or individuals vaccinated with inactivated whole virus vaccines.

Possible Alterations of Imaging Patterns in Computed Tomography for Delta-VOC of SARS-CoV-2.

BACKGROUND: So far, typical findings for COVID-19 in computed tomography (CT) have been described as bilateral, multifocal ground glass opacities (GGOs) and consolidations, as well as intralobular and interlobular septal thickening. On the contrary, round consolidations with the halo sign are considered uncommon and are typically found in fungal infections, such as invasive pulmonary aspergillosis. The authors recently observed several patients with COVID-19 pneumonia presenting with round, multifocal consolidations accompanied by a halo sign. As this may indicate alterations of CT morphology based on the virus variant, the aim of this study was to investigate this matter in more detail. METHODS: 161 CT scans of patients with confirmed SARS-CoV-2 infection (RT-PCR within 2 days of CT) examined between January 2021 and September 15, 2021 were included. Follow-up examinations, patients with invasive ventilation at the time of CT, and patients with insufficient virus typing for variants of concern (VOC) were excluded. CT scans were assessed for vertical and axial distribution of pulmonary patterns, degree of involvement, uni- vs. bilaterality, reticulations, and other common findings. The mean density of representative lesions was assessed in Hounsfield units. Results were compared using Mann-Whitney U-tests, Student's t-rests, descriptive statistics, and Fisher's exact tests. RESULTS: 75 patients did not meet the inclusion criteria. Therefore, 86/161 CT scans of unique patients were analyzed. PCR VOC testing confirmed manifestation of the Delta-VOC SARS-CoV-2 in 22 patients, 39 patients with Alpha-VOC and the remaining 25 patients with Non-VOC SARS-CoV-2 infections. Three patients with the Delta-VOC demonstrated multiple pulmonary masses or nodules with surrounding halo sign, whereas no patients with either Alpha-VOC (p = 0.043) or non-VOC (p = 0.095) demonstrated these findings. All three patients were admitted to normal wards and had no suspicion of a pulmonary co-infection. Patients with Delta-VOC were less likely to have ground glass opacities compared to Alpha-VOC (7/22 or 31.8 % vs. 4/39 or 10.3 %; p < 0.001), whereas a significant difference has not been observed between Delta-VOC and non-VOC (5/25 or 20 %; p = 0.348). The mean representative density of lesions did not show significant differences between the studied cohorts. CONCLUSION: In this study 3 out of 22 patients (13.6 %) with Delta-VOC presented with bilateral round pulmonary masses or nodules with surrounding halo signs, which has not been established as a notable imaging pattern in COVID-19 pneumonia yet. Compared to the other cohorts, a lesser percentage of patients with Delta-VOC presented with ground glass opacities. Based on these results Delta-VOC might cause a divergence in CT-morphologic phenotype. KEY POINTS: · Until recently, CT-morphologic signs of COVID-19 pneumonia have been presumed to be uncontroversially understood. Yet, recently the authors observed diverging pulmonary alterations in patients infected with Delta-VOC.. · These imaging alterations included round pulmonary masses or nodules with surrounding halo sign.. · These imaging alterations have not yet been established as typical for COVID-19 pneumonia, yet.. · Based on these results, Delta-VOC could impose a divergence of CT-morphologic phenotype.. CITATION FORMAT: · Yüksel C, Sähn M, Kleines M et al. Possible Alterations of Imaging Patterns in Computed Tomography for Delta-VOC of SARS-CoV-2 . Fortschr Röntgenstr 2022; 194: 1229 - 1241.

Evaluation of the QuantiFERON SARS-CoV-2 interferon-É£ release assay in mRNA-1273 vaccinated health care workers.

Current studies focus on cellular and humoral immunity induced by novel SARS-CoV-2 vaccines. Non-responders to vaccinations are not uncommonly encountered in clinical medicine (e.g. in the field of hepatitis B). Whereas vaccine-induced humoral immunity against SARS-CoV-2 is compromised by emerging Variants of Concern (VOCs), cellular immunity against SARS-CoV-2 is emerging as resilient against VOCs. Thus commercially available test kits for diagnostic laboratories designed to evaluate cellular immune responses to SARS-CoV-2 are urgently needed. Here we evaluated the novel QuantiFERON SARS-CoV-2 assay (Qiagen) measuring INF-É£ release induced by two spike-derived peptide pools (Ag1 and Ag2) in a cohort of health care workers vaccinated with the mRNA-1273 vaccine and confirmed humoral response. Our study indicates the usefulness of this novel assay for routine laboratories to evaluate cellular immunity against SARS-CoV-2 in response to mRNA-1273 vaccination.

Determination of SARS-CoV-2 antibodies with assays from Diasorin, Roche and IDvet.

There is an ongoing need for highly reliable serological assays to detect individuals with past SARS-CoV-2 infection. Using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR, we investigated the sensitivity and specificity of the Liaison SARS-CoV-2 S1/S2 IgG assay (DiaSorin), the Elecsys Anti-SARS-CoV-2 assay (Roche), and the ID Screen SARS-CoV-2-N IgG indirect kit (IDVet). We determined a sensitivity of 95.5 %, 95.5 %, and 100 % and a specificity of 90.5 %, 96.2 %, and 92.5 % for the DiaSorin assay, the Roche assay, and the IDVet assay, respectively. We conclude that serologic assays combining very high sensitivity and specificity are still not commercially available for SARS-CoV-2. For maximizing sensitivity and specificity of SARS-CoV-2 serological diagnostics, the combination of two assays may be helpful.

Comparison of the SARS-CoV-2 Rapid antigen test to the real star Sars-CoV-2 RT PCR kit.

There is an ongoing need for reliable antigen assays for timely and easy detection of individuals with acute SARS-CoV-2 infection. Using 75 swabs from patients previously tested positive by SARS-CoV-2 PCR and 75 swabs from patients previously tested negative by SARS-CoV-2 PCR, we investigated the sensitivity and specificity of the SARS-CoV-2 Rapid Antigen Test (Roche). We determined a specificity of 96 %. The assay's sensitivity with samples with a cycle threshold of < 25, 25 - <30, 30 - <35, and> = 35 was 100 %, 95 %, 44.8 % and 22.2 %, respectively. We conclude that sensitivity and specificity of the antigen assay is inferior to the PCR assay. However, the antigen assay may be a quick and easy to perform alternative for differentiation of individuals contagious for SARS-CoV-2 from non-contagious individuals.

Development of Fast and Portable Frequency Magnetic Mixing-Based Serological SARS-CoV-2-Specific Antibody Detection Assay.

A novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in December 2019, causing an ongoing, rapidly spreading global pandemic. Worldwide, vaccination is now expected to provide containment of the novel virus, resulting in an antibody-mediated immunity. To verify this, serological antibody assays qualitatively as well as quantitatively depicting the amount of generated antibodies are of great importance. Currently available test methods are either laboratory based or do not have the ability to indicate an estimation about the immune response. To overcome this, a novel and rapid serological magnetic immunodetection (MID) point-of-care (PoC) assay was developed, with sensitivity and specificity comparable to laboratory-based DiaSorin Liaison SARS-CoV-2 S1/S2 IgG assay. To specifically enrich human antibodies against SARS-CoV-2 in immunofiltration columns (IFCs) from patient sera, a SARS-CoV-2 S1 antigen was transiently produced in plants, purified and immobilized on the IFC. Then, an IgG-specific secondary antibody could bind to the retained antibodies, which was finally labeled using superparamagnetic nanoparticles. Based on frequency magnetic mixing technology (FMMD), the magnetic particles enriched in IFC were detected using a portable FMMD device. The obtained measurement signal correlates with the amount of SARS-CoV-2-specific antibodies in the sera, which could be demonstrated by titer determination. In this study, a MID-based assay could be developed, giving qualitative as well as semiquantitative results of SARS-CoV-2-specific antibody levels in patient's sera within 21 min of assay time with a sensitivity of 97% and a specificity of 92%, based on the analysis of 170 sera from hospitalized patients that were tested using an Food and Drug Administration (FDA)-certified chemiluminescence assay.

Accuracy of Chest CT for Differentiating COVID-19 from COVID-19 Mimics.

PURPOSE: To determine the performance of radiologists with different levels of expertise regarding the differentiation of COVID-19 from other atypical pneumonias. Chest CT to identify patients suffering from COVID-19 has been reported to be limited by its low specificity for distinguishing COVID-19 from other atypical pneumonias ("COVID-19 mimics"). Meanwhile, the understanding of the morphologic patterns of COVID-19 has improved and they appear to be fairly specific. MATERIALS AND METHODS: Between 02/2020 and 04/2020, 60 patients with COVID-19 pneumonia underwent chest CT in our department. Cases were matched with a comparable control group of 60 patients of similar age, sex, and comorbidities, who underwent chest CT prior to 01/2020 for atypical pneumonia caused by other pathogens. Included were other viral, fungal, and bacterial pathogens. All 120 cases were blinded to patient history and were reviewed independently by two radiologists and two radiology residents. Readers rated the probability of COVID-19 pneumonia according to the COV-RADS classification system. Results were analyzed using Clopper-Pearson 95 % confidence intervals, Youden's Index for test quality criteria, and Fleiss' kappa statistics. RESULTS: Overall, readers were able to correctly identify the presence of COVID-19 pneumonia in 219/240 (sensitivity: 91 %; 95 %-CI; 86.9 %-94.5 %), and to correctly attribute CT findings to COVID-19 mimics in 159/240 ratings (specificity: 66.3 %; 59.9 %-72.2 %), yielding an overall diagnostic accuracy of 78.8 % (378/480; 74.8 %-82.3 %). Individual reader accuracy ranged from 74.2 % (89/120) to 84.2 % (101/120) and did not correlate significantly with reader expertise. Youden's Index was 0.57. Between-reader agreement was moderate (κ = 0.53). CONCLUSION: In this enriched cohort, radiologists were able to distinguish COVID-19 from "COVID-19 mimics" with moderate diagnostic accuracy. Accuracy did not correlate with reader expertise. KEY POINTS: · In a scenario of direct comparison (no negative findings), CT allows the differentiation of COVID-19 from other atypical pneumonias ("COVID mimics") with moderate accuracy.. · Reader expertise did not significantly influence these results.. · Despite similar patterns and distributions of pulmonary findings, radiologists were able to estimate the probability of COVID-19 pneumonia using the COV-RADS classification in a standardized manner in the larger proportion of cases.. CITATION FORMAT: · Sähn M, Yüksel C, Keil S et al. Accuracy of Chest CT for Differentiating COVID-19 from COVID-19 Mimics. Fortschr Röntgenstr 2021; 193: 1081 - 1091.

Time on previous renal replacement therapy is associated with worse outcomes of COVID-19 in a regional cohort of kidney transplant and dialysis patients.

ABSTRACT: Chronic renal replacement therapy by either a kidney transplant (KTX) or hemodialysis (HD) predisposes patients to an increased risk for adverse outcomes of COVID-19. However, details on this interaction remain incomplete. To provide further characterization, we undertook a retrospective observational cohort analysis of the majority of the hemodialysis and renal transplant population affected by the first regional outbreak of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) in Germany. In a region of 250,000 inhabitants we identified a total of 21 cases with SARS-CoV-2 among 100 KTX and 260 HD patients, that is, 7 KTX with COVID-19, 14 HD with COVID-19, and 3 HD with asymptomatic carrier status. As a first observation, KTX recipients exhibited trends for a higher mortality (43 vs 18%) and a higher proportion of acute respiratory distress syndrome (ARDS) (57 vs 27%) when compared to their HD counterparts. As a novel finding, development of ARDS was significantly associated with the time spent on previous renal replacement therapy (RRT), defined as the composite of dialysis time and time on the transplant (non-ARDS 4.3 vs ARDS 10.6 years, P = .016). Multivariate logistic regression analysis showed an OR of 1.7 per year of RRT. The association remained robust when analysis was confined to KTX patients (5.1 vs 13.2 years, P = .002) or when correlating the time spent on a renal transplant alone (P = .038). Similarly, longer RRT correlated with death vs survival (P = .0002). In conclusion our data suggest renal replacement vintage as a novel risk factor for COVID-19-associated ARDS and death. The findings should be validated by larger cohorts.

Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19.

BACKGROUND: Some patients with Corona Virus Disease 2019 (COVID-19) develop a severe clinical course with acute respiratory distress syndrome (ARDS) and fatal outcome. Clinical manifestations and biomarkers in early stages of disease with relevant predictive impact for outcomes remain largely unexplored. We aimed to identify parameters which are significantly different between subgroups. DESIGN: 125 patients with COVID-19 were analysed. Patients with ARDS (N = 59) or non-ARDS (N = 66) were compared, as well as fatal outcome versus survival in the two groups. KEY RESULTS: ARDS and non-ARDS patients did not differ with respect to comorbidities or medication on developing a fatal outcome versus survival. Body mass index was higher in patients with ARDS versus non-ARDS (p = 0.01), but not different within the groups in survivors versus non-survivors. Interleukin-6 levels on admission were higher in patients with ARDS compared to non-ARDS as well as in patients with fatal outcome versus survivors, whereas lymphocyte levels were lower in the different subgroups (all p<0.05). There was a highly significant 3.5-fold difference in fever load in non-survivors compared to survivors (p<0.0001). Extrapulmonary viral spread was detected more often in patients with fatal outcome compared to survivors (P = 0.01). Further the detection of SARS-CoV-2 in serum showed a significantly more severe course and an increased risk of death (both p<0.05). CONCLUSIONS: We have identified early risk markers for a severe clinical course, like ARDS or fatal outcome. This data might help develop a strategy to address new therapeutic options early in patients with COVID-19 and at high risk for fatal outcome.

Comparison of four new commercial serologic assays for determination of SARS-CoV-2 IgG.

BACKGROUND: Facing the ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for serological assays identifying individuals with past coronavirus disease 2019 (COVID-19). STUDY DESIGN: Our study is the first to compare four new commercially available assays using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR: the anti SARS-CoV-2 ELISA (IgG) (Euroimmun, Germany), the EDI New Coronavirus COVID-19 IgG ELISA, (Epitope diagnostics (EDI), USA), the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Germany), and the SARS-CoV-2 Virachip IgG (Viramed, Germany). RESULTS: We found a sensitivity of 86.4 %, 100 %, 86.4 %, and 77.3 % and a specificity of 96,2 %, 88,7 %, 100 %, and 100 % for the Euroimmun assay, the EDI assay, the Mikrogen assay, and the Viramed assay, respectively. CONCLUSIONS: Commercially available SARS-CoV-2 IgG assays have a sufficient specificity and sensitivity for identifying individuals with past SARS-CoV-2 infection.