How to exclude pulmonary embolism in patients hospitalized with COVID-19: a comparison of predictive scores.

BACKGROUND: Pulmonary embolism (PE) is an important complication of Coronavirus disease 2019 (COVID-19). COVID-19 is associated with respiratory impairment and a pro-coagulative state, rendering PE more likely and difficult to recognize. Several decision algorithms relying on clinical features and D-dimer have been established. High prevalence of PE and elevated Ddimer in patients with COVID-19 might impair the performance of common decision algorithms. Here, we aimed to validate and compare five common decision algorithms implementing age adjusted Ddimer, the GENEVA, and Wells scores as well as the PEGeD- and YEARS-algorithms in patients hospitalized with COVID-19. METHODS: In this single center study, we included patients who were admitted to our tertiary care hospital in the COVID-19 Registry of the LMU Munich. We retrospectively selected patients who received a computed tomography pulmonary angiogram (CTPA) or pulmonary ventilation/perfusion scintigraphy (V/Q) for suspected PE. The performances of five commonly used diagnostic algorithms (age-adjusted D-dimer, GENEVA score, PEGeD-algorithm, Wells score, and YEARS-algorithm) were compared. RESULTS: We identified 413 patients with suspected PE who received a CTPA or V/Q confirming 62 PEs (15%). Among them, 358 patients with 48 PEs (13%) could be evaluated for performance of all algorithms. Patients with PE were older and their overall outcome was worse compared to patients without PE. Of the above five diagnostic algorithms, the PEGeD- and YEARS-algorithms performed best, reducing diagnostic imaging by 14% and 15% respectively with a sensitivity of 95.7% and 95.6%. The GENEVA score was able to reduce CTPA or V/Q by 32.2% but suffered from a low sensitivity (78.6%). Age-adjusted D-dimer and Wells score could not significantly reduce diagnostic imaging. CONCLUSION: The PEGeD- and YEARS-algorithms outperformed other tested decision algorithms and worked well in patients admitted with COVID-19. These findings need independent validation in a prospective study.

Validation of the SACOV-19 score for identifying patients at risk of complicated or more severe COVID-19: a prospective study.

PURPOSE: Identification of patients at risk of complicated or more severe COVID-19 is of pivotal importance, since these patients might require monitoring, antiviral treatment, and hospitalization. In this study, we prospectively evaluated the SACOV-19 score for its ability to predict complicated or more severe COVID-19. METHODS: In this prospective multicenter study, we included 124 adult patients with acute COVID-19 in three German hospitals, who were diagnosed in an early, uncomplicated stage of COVID-19 within 72 h of inclusion. We determined the SACOV-19 score at baseline and performed a follow-up at 30 days. RESULTS: The SACOV-19 score's AUC was 0.816. At a cutoff of > 3, it predicted deterioration to complicated or more severe COVID-19 with a sensitivity of 94% and a specificity of 55%. It performed significantly better in predicting complicated COVID-19 than the random tree-based SACOV-19 predictive model, the CURB-65, 4C mortality, or qCSI scores. CONCLUSION: The SACOV-19 score is a feasible tool to aid decision making in acute COVID-19.

Evidence for increased SARS-CoV-2 susceptibility and COVID-19 severity related to pre-existing immunity to seasonal coronaviruses.

The importance of pre-existing immune responses to seasonal endemic coronaviruses (HCoVs) for the susceptibility to SARS-CoV-2 infection and the course of COVID-19 is the subject of an ongoing scientific debate. Recent studies postulate that immune responses to previous HCoV infections can either have a slightly protective or no effect on SARS-CoV-2 pathogenesis and, consequently, be neglected for COVID-19 risk stratification. Challenging this notion, we provide evidence that pre-existing, anti-nucleocapsid antibodies against endemic α-coronaviruses and S2 domain-specific anti-spike antibodies against ß-coronavirus HCoV-OC43 are elevated in patients with COVID-19 compared to pre-pandemic donors. This finding is particularly pronounced in males and in critically ill patients. Longitudinal evaluation reveals that antibody cross-reactivity or polyclonal stimulation by SARS-CoV-2 infection are unlikely to be confounders. Thus, specific pre-existing immunity to seasonal coronaviruses may increase susceptibility to SARS-CoV-2 and predispose individuals to an adverse COVID-19 outcome, guiding risk management and supporting the development of universal coronavirus vaccines.

Evidence for increased SARS-CoV-2 susceptibility and COVID-19 severity related to pre-existing immunity to seasonal coronaviruses

Wratil et al. find specific antibody responses against seasonal human coronaviruses, which cause the common cold, to be elevated in patients with COVID-19 compared to pre-pandemic blood donors. This specific immunity is likely pre-existing in patients and increases their susceptibility to SARS-CoV-2 and severity of COVID-19.

Genomic epidemiology reveals multiple introductions of SARS-CoV-2 followed by community and nosocomial spread, Germany, February to May 2020.

BackgroundIn the SARS-CoV-2 pandemic, viral genomes are available at unprecedented speed, but spatio-temporal bias in genome sequence sampling precludes phylogeographical inference without additional contextual data.AimWe applied genomic epidemiology to trace SARS-CoV-2 spread on an international, national and local level, to illustrate how transmission chains can be resolved to the level of a single event and single person using integrated sequence data and spatio-temporal metadata.MethodsWe investigated 289 COVID-19 cases at a university hospital in Munich, Germany, between 29 February and 27 May 2020. Using the ARTIC protocol, we obtained near full-length viral genomes from 174 SARS-CoV-2-positive respiratory samples. Phylogenetic analyses using the Auspice software were employed in combination with anamnestic reporting of travel history, interpersonal interactions and perceived high-risk exposures among patients and healthcare workers to characterise cluster outbreaks and establish likely scenarios and timelines of transmission.ResultsWe identified multiple independent introductions in the Munich Metropolitan Region during the first weeks of the first pandemic wave, mainly by travellers returning from popular skiing areas in the Alps. In these early weeks, the rate of presumable hospital-acquired infections among patients and in particular healthcare workers was high (9.6% and 54%, respectively) and we illustrated how transmission chains can be dissected at high resolution combining virus sequences and spatio-temporal networks of human interactions.ConclusionsEarly spread of SARS-CoV-2 in Europe was catalysed by superspreading events and regional hotspots during the winter holiday season. Genomic epidemiology can be employed to trace viral spread and inform effective containment strategies.

Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.

Prediction of COVID-19 deterioration in high-risk patients at diagnosis: an early warning score for advanced COVID-19 developed by machine learning.

PURPOSE: While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization. METHODS: We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16). RESULTS: The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (n = 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface. CONCLUSION: We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19.

[Update 2021: COVID-19 from the perspective of gastroenterology]. / Update 2021: COVID-19 aus Sicht der Gastroenterologie.

During COVID 19 pandemic patients typically present with respiratory symptoms. However, in a significant number of patients the gastrointestinal tract is also involved in the disease. Up to 20 % of patients suffering from gastrointestinal symptoms. New insights in pathophysiological aspects might open new therapeutic concepts. This up-date includes current data regarding epidemiology of gastrointestinal symptoms in COVID 19, its role for prognosis and specific risks in relation to immunosuppressive therapies and underlying diseases.

Dynamics of SARS-CoV-2 shedding in the respiratory tract depends on the severity of disease in COVID-19 patients.

A fraction of COVID-19 patients progress to a severe disease manifestation with respiratory failure and the necessity of mechanical ventilation. Identifying patients at risk is critical for optimised care and early therapeutic interventions. We investigated the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding relative to disease severity.We analysed nasopharyngeal and tracheal shedding of SARS-CoV-2 in 92 patients with diagnosed COVID-19. Upon admission, standardised nasopharyngeal swab or sputum samples were collected. If patients were mechanically ventilated, endotracheal aspirate samples were additionally obtained. Viral shedding was quantified by real-time PCR detection of SARS-CoV-2 RNA.45% (41 out of 92) of COVID-19 patients had a severe disease course with the need for mechanical ventilation (severe group). At week 1, the initial viral shedding determined from nasopharyngeal swabs showed no significant difference between nonsevere and severe cases. At week 2, a difference could be observed as the viral shedding remained elevated in severely ill patients. A time-course of C-reactive protein, interleukin-6 and procalcitonin revealed an even more protracted inflammatory response following the delayed drop of virus shedding load in severely ill patients. A significant proportion (47.8%) of patients showed evidence of prolonged viral shedding (>17 days), which was associated with severe disease courses (73.2%).We report that viral shedding does not differ significantly between severe and nonsevere COVID-19 cases upon admission to the hospital. Elevated SARS-CoV-2 shedding in the second week of hospitalisation, a systemic inflammatory reaction peaking between the second and third week, and prolonged viral shedding are associated with a more severe disease course.

Influence of COVID-19 Pandemic on Endoscopic Procedures in Two European Large-Capacity Endoscopy Units: "Keep Calm, Keep Safe and Scope on?"

BACKGROUND: The COVID-19-pandemic poses challenges to the medical system and especially to endoscopic staff and patients. National, European and International societies provided recommendations on how to safely perform endoscopic procedures during the current pandemic. Until now, the effect of the current pandemic on tertiary endoscopy centers has not been reported. OBJECTIVE: The aim of this was to analyze the influence of the early SARS-CoV2-pandemic on endoscopic care and work flow in 2 European tertiary endoscopy units. METHODS: Data from 2 tertiary endoscopy units (Katowice and Munich) were retrospectively collected during the early pandemic and compared to an equivalent pre-pandemic period. Data include procedures, complications, benchmarks, and influence on endoscopy training. RESULTS: During the early pandemic, we noted a highly significant decrease (49.1%) in the overall number of all endoscopies with a significant increase in therapeutic procedures. Besides, there were no significant differences in the number of urgent endoscopic retrograde cholangiopancreatography or interventional endoscopic ultrasound procedures. The exceptional situation reduced endoscopic procedures performed by trainees significantly. CONCLUSIONS: The SARS-CoV2-pandemic halved the endoscopy service of 2 tertiary centers while maintaining an urgent therapeutic service. Recommended personal safety measures in endoscopy proved to be efficient and safe in preventing SARS-CoV2 infection of staff or spreading. Unnecessarily, the SARS-CoV2 pandemic prevented routine endoscopy training.

[COVID-19 from a gastroenterological perspective]. / COVID-19 aus der Sicht der Gastroenterologie.

COVID 19, caused by SARS-CoV2, a new variant of coronaviruses, typically presents with respiratory symptoms. However, in a significat number of patients different organs are involved in the disease, often including gastrointestinal symptoms. These could include loss of appetite, vomiting, abdominal pain and diarrhea, with diarrhea being associated with a more severe course of COVID-19. Because viral RNA can be detected in fecal samples, some implications for clinical routine in diagnostic and therapeutic procedures are grown. Until yet, no clear evidence is given regarding fecal-oral transmission of SARS-CoV2.

SARS-CoV-2 prevalence in an asymptomatic cancer cohort - results and consequences for clinical routine.

BACKGROUND: Starting in December 2019, the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confronts the world with an unprecedented challenge. With no vaccine or drug being currently available to control the pandemic spread, prevention and PCR (Polymerase chain reaction) testing becomes a crucial pillar of medical systems. Aim of the present study was to report on the first results of the measures taken in a large German Department of Radiation Oncology, including PCR testing of asymptomatic cancer patients. METHODS: Pandemic-adapted hygiene regulations and prevention measures for patients and staff were implemented. A visiting ban on both wards was implemented from the beginning and medical staff and patients were required to wear face masks at all times. The waiting rooms were rearranged to ensure distance between patients of at least 1.5 m. Clinical follow up was mainly done by telephone and all patients had to complete a questionnaire regarding symptoms and contacts with COVID-19 patients before entering our department. Educational documents were created for patients to raise awareness of symptoms and avoidance strategies for interactions with other people. Indications for therapy and fractionation schemes were adapted when possible. In a subsequent step, all new asymptomatic patients were tested via nasopharyngeal swab at our screening station shortly before their simulation CT. RESULTS: All these measures and implementations have been well accepted semiquantitatively measured by the consent received from patients and staff. Regarding the PCR testing, only 1 out of 139 asymptomatic patients of our cohort so far tested positive for SARS-CoV-2, reflecting a prevalence of 0.72% in this cancer patient population. Up to this point no staff members was tested positive. The start of the treatment for the PCR-positive patient was deferred for 2 weeks. CONCLUSION: Due to the pandemic-adapted implementations, our department seems well prepared during this crisis. The initial screening helps to identify asymptomatic COVID-19 patients in order to protect other patients and our staff from infection and the observed PCR prevalence is in line with comparable studies. A regular PCR testing (e.g. twice a week) of all patients and staff would in principle be desirable but is limited due to testing capacities at present.