Impaired humoral immunity to BQ.1.1 in convalescent and vaccinated patients.

Determining SARS-CoV-2 immunity is critical to assess COVID-19 risk and the need for prevention and mitigation strategies. We measured SARS-CoV-2 Spike/Nucleocapsid seroprevalence and serum neutralizing activity against Wu01, BA.4/5 and BQ.1.1 in a convenience sample of 1,411 patients receiving medical treatment in the emergency departments of five university hospitals in North Rhine-Westphalia, Germany, in August/September 2022. 62% reported underlying medical conditions and 67.7% were vaccinated according to German COVID-19 vaccination recommendations (13.9% fully vaccinated, 54.3% one booster, 23.4% two boosters). We detected Spike-IgG in 95.6%, Nucleocapsid-IgG in 24.0%, and neutralization against Wu01, BA.4/5 and BQ.1.1 in 94.4%, 85.0%, and 73.8% of participants, respectively. Neutralization against BA.4/5 and BQ.1.1 was 5.6- and 23.4-fold lower compared to Wu01. Accuracy of S-IgG detection for determination of neutralizing activity against BQ.1.1 was reduced substantially. We explored previous vaccinations and infections as correlates of BQ.1.1 neutralization using multivariable and Bayesian network analyses. Given a rather moderate adherence to COVID-19 vaccination recommendations, this analysis highlights the need to improve vaccine-uptake to reduce the COVID-19 risk of immune evasive variants. The study was registered as clinical trial (DRKS00029414).

Evaluation of a new COVID-19 triage algorithm in the emergency department including combined antigen and PCR-testing: A case-control study.

The coronavirus disease 2019 (COVID-19) pandemic is a major challenge for global healthcare systems. Early and safe triage in the emergency department (ED) is crucial for proper therapy. However, differential diagnosis remains challenging. Rapid antigen testing (RAT) may help to improve early triage and patient safety. We performed a retrospective study of 234 consecutive patients with suspected COVID-19 who presented to our ED in November 2020. All underwent SARS-CoV-2-nasopharyngeal swab testing using both RAT and reverse transcription polymerase chain reaction (RT-PCR). The inpatient treatment was established according to an empirically developed triage algorithm. The accuracy of the suggested algorithm was analyzed based on the rate of outpatients returning within 7 days and inpatients staying for less than 48 hours. COVID-19 inpatients and outpatients were compared for symptoms, vital signs, and C-reactive protein levels. Of the 221 included patients with suspected COVID-19 infection, the diagnosis could be confirmed in 120 patients (54.3%) by a positive RT-PCR result, whereas only 72% of those had a positive antigen test. Of the 56 COVID-19 outpatients, three returned within 7 days with the need for hospital treatment due to clinical deterioration. Among the 64 COVID-19 inpatients, 4 were discharged within 48 hours, whereas 60 stayed longer (mean duration 10.2 days). The suggested triage algorithm was safe and efficient in the first 234 consecutive patients. RAT can confirm a diagnosis in 72% of PCR proven COVID-19 patients and allows early cohort isolation as an important way to save hospital capacity.

Medical and cardio-vascular emergency department visits during the COVID-19 pandemic in 2020: is there a collateral damage? A retrospective routine data analysis.

BACKGROUND: In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. METHODS: Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). RESULTS: A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was - 14% [CI (- 11)-(- 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [- 16%; CI (- 13)-(- 19)], less urgent [- 18%; CI (- 12)-(- 22)] and non-admitted cases [- 17%; CI (- 13)-(- 20)] in particular during the second wave. During the entire observation period admissions for chest pain [- 13%; CI (- 21)-2], myocardial infarction [- 2%; CI (- 9)-11] and heart failure [- 2%; CI (- 10)-6] were less affected and remained comparable to the previous year. CONCLUSIONS: ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies.

[Wave riding - 12 months of COVID-19 in a German tertiary care center]. / Wellenreiten ­ 12 Monate COVID-19 im Maximalversorger.

INTRODUCTION: With more than 1400 COVID-19 inpatients, the university hospital of Essen is the main regional caregiver during COVID-19 pandemic. We present outcome data of our inpatients during the first 12 months of pandemic and our derived clinical care concepts. METHODS: Retrospective analysis of all 1396 COVID-19 inpatients presenting between March, 1st of 2020 and February, 28th of 2021 for comorbidities, survival and complications. Group comparison between patients receiving standard care and those requiring intermediate/ intensive care. RESULTS: Mortality rate of all inpatients was 19,8 % (277/ 1396), whereas 10.6 % (93/877) of the patients with standard care and 35.5 % (184/519) of those with intermediate/intensive care died during hospital stay. Age above 60 years, obesity, need for mechanical ventilation, nitric oxide therapy, ECMO and acute renal failure as well as stroke during the clinical course were independent predictors of mortality. CONCLUSIONS: The mortality of both patient groups ranges within the numbers published by other international groups. The vast impact of usual comorbidities could be observed as well as the high rate of complications in serious ill COVID-19 patients. The mean age of both patient groups was lower than expected (60 years standard care versus 63 years intermediate/ intensive care). A maximum of patient and staff protection measures, a fast and efficient testing strategy during primary triage, standardized concepts from emergency department to intensive care units and dynamic adjustment of resources to daily changing needs can ensure a high quality of care even during peak of pandemic.

What about the others: differential diagnosis of COVID-19 in a German emergency department.

BACKGROUND: The ongoing COVID-19 pandemic remains a major challenge for worldwide health care systems and in particular emergency medicine. An early and safe triage in the emergency department (ED) is especially crucial for proper therapy. Clinical symptoms of COVID-19 comprise those of many common diseases; thus, differential diagnosis remains challenging. METHOD: We performed a retrospective study of 314 ED patients presenting with conceivable COVID-19 symptoms during the first wave in Germany. All were tested for COVID-19 with SARS-Cov-2-nasopharyngeal swabs. Forty-seven patients were positive. We analyzed the 267 COVID-19 negative patients for their main diagnosis and compared COVID-19 patients with COVID-19 negative respiratory infections for differences in laboratory parameters, symptoms, and vital signs. RESULTS: Among the 267 COVID-19 negative patients, 42.7% had respiratory, 14.2% had other infectious, and 11.2% had cardiovascular diseases. Further, 9.0% and 6.7% had oncological and gastroenterological diagnoses, respectively. Compared to COVID-19 negative airway infections, COVID-19 patients showed less dyspnea (OR 0.440; p = 0.024) but more dysgeusia (OR 7.631; p = 0.005). Their hospital stay was significantly longer (9.0 vs. 5.6 days; p = 0.014), and their mortality significantly higher (OR 3.979; p = 0.014). CONCLUSION: For many common ED diagnoses, COVID-19 should be considered a differential diagnosis. COVID-19 cannot be distinguished from COVID-19 negative respiratory infections by clinical signs, symptoms, or laboratory results. When hospitalization is necessary, the clinical course of COVID-19 airway infections seems to be more severe compared to other respiratory infections. TRIAL REGISTRATION: German Clinical Trial Registry DRKS, DRKS-ID of the study: DRKS00021675 date of registration: May 8th, 2020, retrospectively registered.

[University emergency departments in the corona pandemic-Results from the ReCovER registry]. / Universitäre Notaufnahmen in der Coronapandemie ­ Ergebnisse des ReCovER-Registers.

BACKGROUND: The current COVID-19 pandemic, despite the availability of rapid tests and the start of the vaccination campaign, continues to pose major challenges to emergency departments (ED). Structured collection of demographic, clinical, as well as treatment-related data provides the basis for establishing evidence-based processes and treatment concepts. AIM OF THE WORK: To present the systematic collection of clinical parameters in patients with suspected COVID-19 in the Registry for COVID-19 in the Emergency Room (ReCovER) and descriptive presentation of the first 1000 patients. MATERIALS AND METHODS: Data from patients with suspected COVID-19, regardless of evidence of SARS-CoV­2 infection, are continuously entered into a web-based, anonymized registry in ED at six university hospitals. RESULTS: Between 19 May 2020 and 13 January 2021, 1000 patients were entered into the registry, of whom 594 patients (59.4%) were in the SARS-CoV­2 positive group (PG) and 406 patients (40.6%) were in the negative group (NG). Patients of the PG had significantly fewer pre-existing conditions and a significantly longer latency between symptom onset and presentation to the ED (median 5 vs. 3 days), were more likely to suffer from cough, myalgia, fatigue, and loss of smell/taste and had significantly higher oxygen requirements than NG patients. The rate of severe disease progression was significantly higher in the PG, and persistent symptoms were more common after discharge (11.1 vs. 4.6%). CONCLUSIONS: The multicenter collection of comprehensive clinical data on COVID-19 suspected cases in the ED allows analysis of aspects specific to the situation in Germany in particular. This is essential for a targeted review and adaptation of internationally published strategies.

ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.

OBJECTIVES: The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19. PATIENTS AND METHODS: We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease. CONCLUSIONS: In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.

Transmembrane serine protease 2 Polymorphisms and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Type 2 Infection: A German Case-Control Study.

The transmembrane serine protease 2 (TMPRSS2) is the major host protease that enables entry of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) into host cells by spike (S) protein priming. Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. Functional variants may influence SARS-CoV-2 infection risk and severity of Coronavirus disease 2019 (COVID-19) as well. Therefore, we analyzed the role of SNPs in the gene TMPRSS2 in a German case-control study. We performed genotyping of the SNPs rs2070788, rs383510, and rs12329760 in the gene TMPRSS2 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding their demographics. The CC genotype of TMPRSS2 rs383510 was associated with a 1.73-fold increased SARS-CoV-2 infection risk, but was not correlated to severity of COVID-19. Neither TMPRSS2 rs2070788 nor rs12329760 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. In a multivariable analysis (MVA), the rs383510 CC genotype remained an independent predictor for a 2-fold increased SARS-CoV-2 infection risk. In summary, our report appears to be the first showing that the intron variant rs383510 in the gene TMPRSS2 is associated with an increased risk to SARS-CoV-2 infection in a German cohort.

SARS-CoV-2 rapid antigen test: Fast-safe or dangerous? An analysis in the emergency department of an university hospital.

The use of Antigen point of care tests (AgPOCT) might be an essential tool to fight the coronavirus disease 2019 (COVID-19) pandemic. Manufacturer information indicates a specificity of about 95% and there is a growing interest to use these tests area-wide. Therefore, it is necessary to clarify whether AgPOCT can be used safely for "rule-in" (detection of positive patients) and for "rule-out" (valid negative testing). Two thousand three hundred and seventy-five patients received polymerase chain reaction (PCR) testing and AgPOCT for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of symptoms. The positive predictive value of symptomatic and asymptomatic patients was compared with a cut-off threshold cycle (C t ) value of ≤30 and in total. Five hundrded and fifty-one patients tested positive for the SARS-CoV-2 virus by PCR, of whom 35.2% presented without symptoms. In all patients, regardless of their symptoms or C t values, a sensitivity of 68.9% and a specificity of 99.6% were calculated for AgPOCT. In patients with C t values ≤30, a sensitivity of 80.5% (95% confidence interval: ±1.62) and a specificity of 99.6% were shown for all tests (symptomatic/asymptomatic). Highly infectious patients (C t ≤ 20), regardless of symptoms, were reliably detected by the AgPOCT. In infectious patients with C t values ≤30, the test has a sensitivity of about 80% regardless of COVID-19 typical symptoms, which is apparently less than the 96.52% specificity indicated by the manufacturer. Relevant improvement in test sensitivity by querying the patients who are symptomatic and asymptomatic is also not feasible. We strongly suggest that we critically question the use of AgPOCT for "rule-out," as they only provide a supposed safety.

Which parameters support disposition decision in suspected COVID-19 cases in the emergency department (ED): a German clinical cohort study.

OBJECTIVES: One major goal of the emergency department (ED) is to decide, whether patients need to be hospitalised or can be sent home safely. We aim at providing criteria for these decisions without knowing the SARS-CoV-2 test result in suspected cases. SETTING: Tertiary emergency medicine. PARTICIPANTS: All patients were treated at the ED of the Charité during the pandemic peak and underwent SARS-CoV-2 testing. Patients with positive test results were characterised in detail and underwent a 14-day-follow-up. PRIMARY AND SECONDARY OUTCOME MEASURES: Logistic regression and classification and regression tree (CART) analyses were performed to identify predictors (primary endpoint), which confirm safe discharge. The clinical endpoint was all-cause mortality or need for mechanical ventilation during index stay or after readmission. RESULTS: The primary test population of suspected COVID-19 consisted of n=1255 cases, 45.2% were women (n=567). Of these, n=110 tested positive for SARS-CoV-2 (8.8%). The median age of SARS-CoV-2-positive cases was 45 years (IQR: 33-66 years), whereas the median age of the group tested negative for SARS-CoV-2 was 42 years (IQR: 30-60 years) (p=0.096). 43.6% were directly admitted to hospital care.CART analysis identified the variables oxygen saturation (<95%), dyspnoea and history of cardiovascular (CV) disease to distinguish between high and low-risk groups. If all three variables were negative, most patients were discharged from ED, and the incidence of the clinical endpoint was 0%. The validation cohort confirmed the safety of discharge using these variables and revealed an incidence of the clinical endpoint from 14.3% in patients with CV disease, 9.4% in patients with dyspnoea and 18.2% in patients with O2 satuaration below 95%. CONCLUSIONS: Based on easily available variables like dyspnoea, oxygen saturation, history of CV disease, approximately 25% of patients subsequently confirmed with COVID-19 can be identified for safe discharge. TRIAL REGISTRATION NUMBER: DRKS00023117.

Observational cohort study of neurological involvement among patients with SARS-CoV-2 infection.

BACKGROUND: A growing number of reports suggest that infection with SARS-CoV-2 often leads to neurological involvement; however, data on the incidence and severity are limited to mainly case reports and retrospective studies. METHODS: This prospective, cross-sectional study of 102 SARS-CoV-2 PCR positive patients investigated the frequency, type, severity and risk factors as well as underlying pathophysiological mechanisms of neurological involvement (NIV) in COVID-19 patients. RESULTS: Across the cohort, 59.8% of patients had NIV. Unspecific NIV was suffered by 24.5%, mainly general weakness and cognitive decline or delirium. Mild NIV was found in 9.8%; most commonly, impaired taste or smell. Severe NIV was present in 23.5%; half of these suffered cerebral ischaemia. Incidence of NIV increased with respiratory symptoms of COVID-19. Mortality was higher with increasing NIV severity. Notably, 83.3% with severe NIV had a pre-existing neurological co-morbidity. All cerebrospinal fluid (CSF) samples were negative for SARS-CoV-2 RNA, and SARS-CoV-2 antibody quotient did not suggest intrathecal antibody synthesis. Of the patients with severe NIV, 50% had blood-brain barrier (BBB) disruption and showed a trend of elevated interleukin levels in CSF. Antibodies against neuronal and glial epitopes were detected in 35% of the patients tested. CONCLUSION: Cerebrovascular events were the most frequent severe NIV and severe NIV was associated with high mortality. Incidence of NIV increased with respiratory symptoms and NIV and pre-existing neurological morbidities were independent risk factors for fatality. Inflammatory involvement due to BBB disruption and cytokine release drives NIV, rather than direct viral invasion. These findings might help physicians define a further patient group requiring particular attention during the pandemic.

The influence of IFITM3 polymorphisms on susceptibility to SARS-CoV-2 infection and severity of COVID-19.

BACKGROUND AND AIMS: The interferon-induced transmembrane protein 3 (IFITM3) plays an important role in the adaptive and innate immune response by inhibiting viral membrane hemifusion between the host and viral cell cytoplasm. Single nucleotide polymorphisms (SNPs) in the gene IFITM3 have been associated with susceptibility and severity of influenza or other viral infections. We aimed to analyze the role of SNPs in the gene IFITM3 in SARS-CoV-2 infection. METHODS: We performed genotyping of the SNPs rs12252 and rs34481144 in the gene IFITM3 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics. Neither IFITM3 rs12252 nor rs34481144 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. Interestingly, we observed the putative deleterious rs12252 CC genotype only in SARS-CoV-2-positive patients (N = 2). Also, we found a non-significant higher frequency of rs34481144 A-allele carriers in the patients with 'serious' COVID-19. CONCLUSIONS: In summary, we could not confirm the recently reported influence of polymorphisms in the gene IFITM3 on SARS-CoV-2 infection risk or severity of COVID-19 in a German cohort. Additional studies are needed to clarify the influence of the rs12252 CC genotype on SARS-CoV-2 infection risk and the rs34481144 A-allele on course of COVID-19.

Separating the wheat from the chaff-COVID-19 in a German emergency department: a case-control study.

BACKGROUND: COVID-19 pandemia is a major challenge to worldwide health care systems. Whereas the majority of disease presents with mild symptoms that can be treated as outpatients, severely ill COVID-19 patients and patients presenting with similar symptoms cross their ways in the emergency department. Especially, the variety of symptoms is challenging with primary triage. Are there parameters to distinguish between proven COVID-19 and without before? How can a safe and efficient management of these inpatients be achieved? METHODS: We conducted a retrospective analysis of 314 consecutive inpatient patients who presented with possible symptoms of COVID-19 in a German emergency department between March and April 2020 and were tested with a SARS-Cov-2 nasopharyngeal swab. Clinical parameters, Manchester Triage System categories, and lab results were compared between patients with positive and negative test results for SARS-Cov-2. Furthermore, we present the existing COVID-19 workflow model of the university hospital in Essen which proved to be efficient during pandemia. RESULTS: Forty-three of the 314 patients (13.7%) were tested positive for COVID-19 by SARS-Cov-2 nasopharyngeal swab. We did not find any laboratory parameter to distinguish safely between patients with COVID-19 and those with similar symptoms. Dysgeusia was the only clinical symptom that was significantly more frequent among COVID-19 patients. CONCLUSION: Dysgeusia seems to be a typical symptom for COVID-19, which occurred in 14% of our COVID-19 patients. However, no valid parameters could be found to distinguish clinically between COVID-19 and other diseases with similar symptoms. Therefore, early testing, a strict isolation policy, and proper personal protection are crucial to maintain workflow and safety of patients and ED staff for the months to come. TRIAL REGISTRATION: German Clinical Trials registry, DRKS00021675.