Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Tyrol, Austria: Updated analysis involving 22,607 blood donors covering the period October 2021 to April 2022 (preprint)

Background Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. Methods We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Results Median age of participants was 45.3 years (IQR: 30.9-55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8–86.0%) to 95.8% (94.9–96.4%) and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271–296) to 1437 (1360–1518) BAU/mL. The percentages of participants in categories with undetectable levels, and detectable levels at <500, 500–<1000, 1000–<2000, 2000–<3000, and ≥3,000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2–19.9; p- value < 0.001). Conclusion Anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.

Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae (preprint)

Background Olfactory dysfunction (OD) often accompanies acute coronavirus disease 2019 (COVID-19) and its sequelae. Herein, we investigated OD during COVID-19 recovery in the context of other symptoms, quality of life, physical and mental health. Methods Symptom recovery patterns were analyzed in a bi-national, ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and a multi-center observational cross-sectional cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up) with multi-dimensional scaling, association rule mining and partitioning around medoids clustering. Results Both in the ambulatory collective (72%, n = 655/906) and the cross-sectional ambulatory and hospitalized cohort (41%, n = 44/108) self-reported OD was frequent during acute COVID-19, displayed a slow recovery pace (ambulatory: 28 days, cross-sectional: 90 days median recovery time) and commonly co-occurred with taste disorders. In the ambulatory collective, a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorder (>90 days) was identified. This post-acute smell and taste disorder phenotype was characterized by a low frequency of other leading post-acute symptoms including fatigue, respiratory and neurocognitive complaints. Despite a protracted smell and taste dysfunction, this subset had high ratings of physical performance, mental health, and quality of life. Conclusion Our results underline the clinical heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype may represent a distinct COVID-19 recovery pathway characterized by a good recovery of other COVID-19 related symptoms. Study registration ClinicalTrials.gov: NCT04661462 (ambulatory collective), NCT04416100 (cross-sectional cohort).

Who is at risk of poor mental health following COVID-19 outpatient management? (preprint)

BackgroundCOVID-19 convalescents are at risk of developing a de novo mental health disorder or of worsening of a pre-existing one. The objectives of our study was to phenotype individuals at highest risk of mental health disorders among COVID-19 outpatients. MethodsWe conducted a binational online survey study with adult non-hospitalized COVID-19 convalescents (Austria/AT: n=1157, Italy/IT: n= 893). Primary endpoints were positive screening for depression and anxiety (PHQ-4, Patient Health Questionnaire) and self-perceived overall mental health and quality of life rated with 4 point Likert scales. Psychosocial stress was surveyed with a modified PHQ stress module. Associations of the mental health with socio-demographic variables, COVID-19 course and recovery data were assessed by multi-parameter random forest and serial univariable modeling. Mental disorder risk subsets were defined by self-organizing map and hierarchical clustering algorithms. The survey analyses are publicly available (https://im2-ibk.shinyapps.io/mental_health_dashboard/). ResultsIn the study cohorts, 4.6 (IT)/6% (AT) of participants reported depression and/or anxiety before to infection. At a median of 79 days (AT)/96 days (IT) post COVID-19 onset, 12.4 (AT)/19.3% (IT) of subjects were screened positive for anxiety and 17.3 (AT)/23.2% (IT) for depression. Over one-fifth of the respondents rated their overall mental health (AT: 21.8%, IT: 24.1%) or quality of life (AT: 20.3%, IT: 25.9%) as fair or poor. In both study collectives, psychosocial stress, high numbers of acute and persistent COVID-19 complaints and the presence of acute neurocognitive symptoms (impaired concentration, confusion, forgetfulness) were the strongest correlates of deteriorating mental health and poor quality of life. In clustering analysis, these variables defined a high risk subset with particularly high propensity of post-COVID-19 mental health impairment and decreased quality of life. Pre-existing depression or anxiety was associated with an increased symptom burden during acute COVID-19 and recovery. ConclusionOur study revealed a bidirectional relationship between COVID-19 symptoms and mental health. We put forward specific acute symptoms of the disease as red flags of mental health deterioration which should prompt general practitioners to identify COVID-19 patients who may benefit from early psychological and psychiatric intervention. Trial registrationClinicalTrials.gov: NCT04661462.

Phenotyping of acute and persistent COVID-19 features in the outpatient setting: exploratory analysis of an international cross-sectional online survey (preprint)

BACKGROUNDLong COVID, defined as presence of COVID-19 related symptoms 28 days or more after the onset of acute SARS-CoV-2 infection, is an emerging challenge to healthcare systems. The objective of this study was to phenotype recovery trajectories of non-hospitalized COVID-19 individuals. METHODSWe performed an international, multi-center, exploratory online survey study on demographics, comorbidities, COVID-19 symptoms and recovery status of non-hospitalized SARS-CoV-2 infected adults (Austria: n=1157), and Italy: n= 893). RESULTSWorking age subjects (Austria median: 43 yrs (IQR: 31 - 53), Italy: 45 yrs (IQR: 35 - 55)) and females (65.1% and 68.3%) predominated the study cohorts. Course of acute COVID-19 was characterized by a high symptom burden (median 13 (IQR: 9 - 18) and 13 (7 - 18) out of 44 features queried), a 47.6 - 49.3% rate of symptom persistence beyond 28 days and 20.9 - 31.9% relapse rate. By cluster analysis, two acute symptom phenotypes could be discerned: the non-specific infection phenotype and the multi-organ phenotype (MOP), the latter encompassing multiple neurological, cardiopulmonary, gastrointestinal and dermatological features. Clustering of long COVID subjects yielded three distinct subgroups, with a subset of 48.7 - 55 % long COVID individuals particularly affected by post-acute MOP symptoms. The number and presence of specific acute MOP symptoms and pre-existing multi-morbidity was linked to elevated risk of long COVID. CONCLUSIONThe consistent findings of two independent cohorts further delineate patterns of acute and post-acute COVID-19 and emphasize the importance of symptom phenotyping of home-isolated COVID-19 patients to predict protracted convalescence and to allocate medical resources. Key PointsO_ST_ABSQuestionC_ST_ABSWhich acute symptom patterns of acute COVID-19 are associated with prolonged symptom persistence, symptom relapse or physical performance impairment? FindingsIn this multicenter international comparative survey study on non-hospitalized SARS- CoV-2 infected adults (Austria: n = 1157, Italy: n = 893) we identified distinct and reproducible phenotypes of acute and persistent features. Acute multi-organ symptoms including neurological and cardiopulmonary manifestations are linked to elevated risk of long COVID. MeaningThese findings suggest to employ symptom phenotyping of home-isolated COVID-19 patients to predict protracted convalescence and to allocate medical resources.