Association between IgG responses against the nucleocapsid proteins of alphacoronaviruses and COVID-19 severity.

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to contain the COVID-19 pandemic. Using a multiplex approach, serum IgG responses against the whole SARS-CoV-2 proteome and the nucleocapsid proteins of endemic human coronaviruses (HCoVs) were measured in SARS-CoV-2-infected donors and healthy controls. COVID-19 severity strongly correlated with IgG responses against the nucleocapsid (N) of SARS-CoV-2 and possibly with the number of viral antigens targeted. Furthermore, a strong correlation between COVID-19 severity and serum responses against N of endemic alpha- but not betacoronaviruses was detected. This correlation was neither caused by cross-reactivity of antibodies, nor by a general boosting effect of SARS-CoV-2 infection on pre-existing humoral immunity. These findings raise the prospect of a potential disease progression marker for COVID-19 severity that allows for early stratification of infected individuals.

Agreement between cardiac output measurements by pulse wave analysis using the Pressure Recording Analytical Method and transthoracic echocardiography in patients with veno-venous extracorporeal membrane oxygenation therapy: An observational method comparison.

BACKGROUND: Measuring cardiac output (CO) is important in patients treated with veno-venous extracorporeal membrane oxygenation (vvECMO) because vvECMO flow and CO need to be balanced. Uncalibrated pulse wave analysis with the Pressure Recording Analytical Method (PRAM) may be suitable to measure CO in patients with vvECMO therapy. OBJECTIVE: To assess the agreement between CO measured by PRAM (PRAM-CO; test method) and CO measured by transthoracic echocardiography (TTE-CO; reference method). DESIGN: A prospective observational method comparison study. SETTING: The ICU of a German university hospital between March and December 2021. PATIENTS: Thirty one adult patients with respiratory failure requiring vvECMO therapy: 29 of the 31 patients (94%) were treated for COVID-19 related respiratory failure. MAIN OUTCOME MEASURES: PRAM-CO and TTE-CO were measured simultaneously at two time points in each patient with at least 20 min between measurements. A radial or femoral arterial catheter-derived blood pressure waveform was used for PRAM-CO measurements. TTE-CO measurements were conducted using the pulsed wave Doppler-derived velocity time integral of the left ventricular outflow tract (LVOT) and the corresponding LVOT diameter. PRAM-CO and TTE-CO were compared using Bland-Altman analysis and the percentage error (PE). We defined a PE of <30% as clinically acceptable. RESULTS: Mean ±â€ŠSD PRAM-CO was 6.86 ±â€Š1.49 l min -1 and mean TTE-CO was 6.94 ±â€Š1.58 l min -1 . The mean of the differences between PRAM-CO and TTE-CO was 0.09 ±â€Š0.73 l min -1 with a lower 95% limit of agreement of -1.34 l min -1 and an upper 95% limit of agreement of 1.51 l min -1 . The PE was 21%. CONCLUSIONS: The agreement between PRAM-CO and TTE-CO is clinically acceptable in adult patients with vvECMO therapy.

Association between somatic symptom disorder and symptoms with daily life impairment after SARS-CoV-2 infection - results from a population-based cross-sectional study

Background Post-COVID syndrome (PCS) is defined by symptom persistence accompanied by daily life impairment (DLI). The association of somatic symptom disorder (SSD) and symptoms with DLI after SARS-CoV-2 infection in the general population is unclear to date. The main objective of the study was to investigate the association of possible SSD, depression, anxiety, and participant-reported symptoms with DLI in a local population sample. Methods Anonymised cross-sectional study. A symptom questionnaire, including the scales Patient Health Questionnaire PHQ-15 (somatisation module), SSD-12 (psychological distress in SSD), PHQ-2 (depression), GAD-2 (anxiety), and FAS (fatigue assessment scale) was sent in 02/2022 to all adult residents of the district Bad Tölz-Wolfratshausen, Germany, who were registered for SARS-CoV-2-infection between 03/2020 and 11/2021 (8925 delivered). Associations between DLI, symptoms and scales were estimated using binary logistic regression models and network analysis. Results 2828 questionnaires (31.7%) were complete. 1486 (52.5%) reported persistent symptoms, and 509 (18.0%) perceived DLI. DLI was strongest associated with self-reported fatigue (OR 7.86;95%CI 5.63–10.97), dyspnea (3.93;2.73–5.67), impaired concentration (3.05;2.17–4.30), SSD-12 (4.36;2.57–7.41), and PHQ-2 (2.48;1.57–3.92). Self-reported fatigue showed the strongest correlation (rp = 0.248) and closest proximity to DLI in network analysis. Conclusion PCS appears as a complex clinical picture in which SSD might play an important role when DLI is present. The pychological burden might partly be explained by the persistent symptoms, which are difficult to treat up to now. Screening for SSD could help in differential diagnostic decision-making to ensure that patients receive appropriate psychosocial interventions for disease coping.

Association between somatic symptom disorder and symptoms with daily life impairment after SARS-CoV-2 infection - results from a population-based cross-sectional study.

BACKGROUND: Post-COVID syndrome (PCS) is defined by symptom persistence accompanied by daily life impairment (DLI). The association of somatic symptom disorder (SSD) and symptoms with DLI after SARS-CoV-2 infection in the general population is unclear to date. The main objective of the study was to investigate the association of possible SSD, depression, anxiety, and participant-reported symptoms with DLI in a local population sample. METHODS: Anonymised cross-sectional study. A symptom questionnaire, including the scales Patient Health Questionnaire PHQ-15 (somatisation module), SSD-12 (psychological distress in SSD), PHQ-2 (depression), GAD-2 (anxiety), and FAS (fatigue assessment scale) was sent in 02/2022 to all adult residents of the district Bad Tölz-Wolfratshausen, Germany, who were registered for SARS-CoV-2-infection between 03/2020 and 11/2021 (8925 delivered). Associations between DLI, symptoms and scales were estimated using binary logistic regression models and network analysis. RESULTS: 2828 questionnaires (31.7%) were complete. 1486 (52.5%) reported persistent symptoms, and 509 (18.0%) perceived DLI. DLI was strongest associated with self-reported fatigue (OR 7.86; 95%CI 5.63-10.97), dyspnea (3.93; 2.73-5.67), impaired concentration (3.05; 2.17-4.30), SSD-12 (4.36; 2.57-7.41), and PHQ-2 (2.48; 1.57-3.92). Self-reported fatigue showed the strongest correlation (rp = 0.248) and closest proximity to DLI in network analysis. CONCLUSION: PCS appears as a complex clinical picture in which SSD might play an important role when DLI is present. The pychological burden might partly be explained by the persistent symptoms, which are difficult to treat up to now. Screening for SSD could help in differential diagnostic decision-making to ensure that patients receive appropriate psychosocial interventions for disease coping.

Association between IgG responses against the nucleocapsid proteins of alphacoronaviruses and COVID-19 severity

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to contain the COVID-19 pandemic. Using a multiplex approach, serum IgG responses against the whole SARS-CoV-2 proteome and the nucleocapsid proteins of endemic human coronaviruses (HCoVs) were measured in SARS-CoV-2-infected donors and healthy controls. COVID-19 severity strongly correlated with IgG responses against the nucleocapsid (N) of SARS-CoV-2 and possibly with the number of viral antigens targeted. Furthermore, a strong correlation between COVID-19 severity and serum responses against N of endemic alpha- but not betacoronaviruses was detected. This correlation was neither caused by cross-reactivity of antibodies, nor by a general boosting effect of SARS-CoV-2 infection on pre-existing humoral immunity. These findings raise the prospect of a potential disease progression marker for COVID-19 severity that allows for early stratification of infected individuals.

Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data.

OBJECTIVES: To estimate the treatment incidence of post-COVID syndrome (postinfectious sequelae present at least 12 weeks following infection) in the context of ambulatory care in Bavaria, Germany, and to establish whether related diagnoses occur more frequently than in patients with no known history of COVID-19. DESIGN: Retrospective cohort analysis of routinely collected claims data. SETTING: Ambulatory care in Bavaria, Germany, observed from January 2020 to March 2022 (data accessed May 2022). PARTICIPANTS: 391 990 patients with confirmed COVID-19 diagnosis, 62 659 patients with other respiratory infection and a control group of 659 579 patients with no confirmed or suspected diagnosis of COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome is diagnosis of post-COVID syndrome documented in ambulatory care. Secondary outcomes are: chronic fatigue syndrome, psychological disorder, fatigue, mild cognitive impairment, disturbances of taste and smell, dyspnoea, pulmonary embolism and myalgia. RESULTS: Among all patients with confirmed COVID-19, 14.2% (95% CI 14.0% to 14.5%) received a diagnosis of a post-COVID syndrome, and 6.7% (95% CI 6.5% to 6.9%) received the diagnosis in at least two quarterly periods during a 2-year follow-up. Compared with patients with other respiratory infections and with controls, patients with COVID-19 more frequently received a variety of diagnoses including chronic fatigue syndrome (1.6% vs 0.6% and 0.3%, respectively), fatigue (13.3% vs 9.2% and 6.0%), dyspnoea (9.9% vs 5.1% and 3.2%) and disturbances of taste and smell (3.2% vs 1.2% and 0.5%). The treatment incidence of post-COVID syndrome was highest among adults aged 40-59 (19.0%) and lowest among children aged below 12 years (2.6%). CONCLUSIONS: Our results demonstrate a moderately high incidence of post-COVID syndrome 2 years after COVID-19 diagnosis. There is an urgent need to find efficient and effective solutions to help patients with dyspnoea, fatigue, cognitive impairment and loss of smell. Guidelines and treatment algorithms, including referral criteria, and occupational and physical therapy, require prompt and coherent implementation.

COVID-19 vaccine hesitancy in people with migratory backgrounds: a cross-sectional study among Turkish- and German-speaking citizens in Munich.

BACKGROUND: This study aimed to investigate the knowledge, attitudes, behaviors, and COVID-19 vaccine hesitancy of people with migratory backgrounds among Turkish- and German-speaking patients in Munich. METHODS: Primary outcomes were the intention to get vaccinated for COVID-19 and COVID-19 knowledge levels (25 true/false items). Other variables included demographics, attitudes to COVID-19 and vaccination (7 items), and behaviors regarding COVID-19 (7 items). The attitude and behavior questions had 5-point Likert scales. Of the 10 Turkish-speaking family physicians in Munich, six agreed to administer Turkish or German questionnaires to consecutive patients in February 2021. Furthermore, participants with either citizenship, country of origin, native language, or place of birth being non-German were categorized as "Having a migratory background." Data from 420 respondents were analyzed. RESULTS: Women constituted 41.4% (n = 174), the mean age was 42.2 ± 15.5 years, 245 (58.3%) preferred the Turkish questionnaire, 348 (82.9%) had a migratory background, and 197 (47.9%) intended to be vaccinated. The mean knowledge, attitude, and behavioral scores were 21.5 ± 3.2 (max = 25), 3.7 ± 0.8 (max = 5), and 4.0 ± 0.5 (max = 5). While 42.3% (n = 145) of the participants with a migratory background considered getting vaccinated, this proportion was 76.5% (n = 52) for non-immigrant Germans (Chi-square = 26.818, p < 0.001). Non-migratory background (odds ratio (OR): 3.082), high attitude scores (OR: 2.877), male sex (OR: 2.185), years of schooling (OR: 1.064), and age (OR: 1.022) were positively associated with vaccination intention. CONCLUSIONS: We suggest initiating or supporting projects run by persons or groups with immigrant backgrounds to attempt to elaborate and change their vaccination attitudes.

COVID-19 assessment in family practice-A clinical decision rule based on self-rated symptoms and contact history.

The study aimed to evaluate the diagnostic accuracy of contact history and clinical symptoms and to develop decision rules for ruling-in and ruling-out SARS-CoV-2 infection in family practice. We performed a prospective diagnostic study. Consecutive inclusion of patients coming for COVID-PCR testing to 19 general practices. Contact history and self-reported symptoms served as index test. PCR testing of nasopharyngeal swabs served as reference standard. Complete data were available from 1141 patients, 605 (53.0%) female, average age 42.2 years, 182 (16.0%) COVID-PCR positive. Multivariable logistic regression showed highest odds ratios (ORs) for "contact with infected person" (OR 9.22, 95% CI 5.61-15.41), anosmia/ageusia (8.79, 4.89-15.95), fever (4.25, 2.56-7.09), and "sudden disease onset" (2.52, 1.55-4.14). Patients with "contact with infected person" or "anosmia/ageusia" with or without self-reported "fever" had a high probability of COVID infection up to 84.8%. Negative response to the four items "contact with infected person, anosmia/ageusia, fever, sudden disease onset" showed a negative predictive value (NPV) of 0.98 (95% CI 0.96-0.99). This was present in 446 (39.1%) patients. NPV of "completely asymptomatic," "no contact," "no risk area" was 1.0 (0.96-1.0). This was present in 84 (7.4%) patients. To conclude, the combination of four key items allowed exclusion of SARS-CoV-2 infection with high certainty. With the goal of 100% exclusion of SARS-CoV-2 infection to prevent the spread of SARS-CoV-2 to the population level, COVID-PCR testing could be saved only for patients with negative response in all items. The decision rule might also help for ruling-in SARS-CoV-2 infection in terms of rapid assessment of infection risk.

SARS-CoV-2 infection and cardiovascular or pulmonary complications in ambulatory care: A risk assessment based on routine data.

BACKGROUND: Risk factors of severe COVID-19 have mainly been investigated in the hospital setting. We investigated pre-defined risk factors for testing positive for SARS-CoV-2 infection and cardiovascular or pulmonary complications in the outpatient setting. METHODS: The present cohort study makes use of ambulatory claims data of statutory health insurance physicians in Bavaria, Germany, with polymerase chain reaction (PCR) test confirmed or excluded SARS-CoV-2 infection in first three quarters of 2020. Statistical modelling and machine learning were used for effect estimation and for hypothesis testing of risk factors, and for prognostic modelling of cardiovascular or pulmonary complications. RESULTS: A cohort of 99 811 participants with PCR test was identified. In a fully adjusted multivariable regression model, dementia (odds ratio (OR) = 1.36), type 2 diabetes (OR = 1.14) and obesity (OR = 1.08) were identified as significantly associated with a positive PCR test result. Significant risk factors for cardiovascular or pulmonary complications were coronary heart disease (CHD) (OR = 2.58), hypertension (OR = 1.65), tobacco consumption (OR = 1.56), chronic obstructive pulmonary disease (COPD) (OR = 1.53), previous pneumonia (OR = 1.53), chronic kidney disease (CKD) (OR = 1.25) and type 2 diabetes (OR = 1.23). Three simple decision rules derived from prognostic modelling based on age, hypertension, CKD, COPD and CHD were able to identify high risk patients with a sensitivity of 74.8% and a specificity of 80.0%. CONCLUSIONS: The decision rules achieved a high prognostic accuracy non-inferior to complex machine learning methods. They might help to identify patients at risk, who should receive special attention and intensified protection in ambulatory care.

The diversity of opinion among general practitioners regarding the threat and measures against COVID-19 - Cross-sectional survey.

BACKGROUND: After the 'first wave' in spring 2020, opinions regarding the threat and measures against COVID-19 seemed to vary among German general practitioners (GPs). OBJECTIVES: To systematically investigate opinions and to identify subgroups of GPs sharing similar views. METHODS: A questionnaire was sent to all 210 practices accredited for undergraduate teaching of family medicine at the Medical Faculty of the Technical University of Munich. Questions addressed personal opinions regarding risks, dilemmas, restrictions and their relaxation associated with COVID-19, and personal fears, symptoms of depression and anxiety. Patterns of strong opinions ('archetypes') were identified using archetypal analysis, a statistical method seeking extremal points in the multidimensional data. RESULTS: One hundred and sixty-one GPs sent back a questionnaire (response rate 77%); 143 (68%) with complete data for all 38 relevant variables could be included in the analysis. We identified four archetypes with subgroups of GPs tending in the direction of these archetypes: a small group of 'Sceptics' (n = 12/8%) considering threats of COVID-19 as overrated and measures taken as exaggerated; 'Hardliners' (n = 34/24%) considering threats high and supporting strong measures; 'Balancers' (n = 77/54%) who also rated the threats high but were more critical about potentially impairing the quality of life of elderly people and children; and 'Anxious' GPs (n = 20/14%) tending to report more fear, depressive and anxiety symptoms. CONCLUSION: Among the participants in this survey, opinions regarding the threat and the measures taken against COVID-19 during the 'first wave' in Germany in spring 2020 varied greatly.