ABSTRACT
Background: Post-COVID Syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence >3 months, subacute symptom onset, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS. Method(s): COVIDOM is a population-based cohort study of PCR-confirmed cases of SARS-CoV-2 infection, recruited through local public health authorities in three German regions. Standardised interviews and in-depth onsite examinations were scheduled 6-12 months post infection. Based upon 12 long-term symptom complexes, we developed a comprehensive PCS severity score in a training cohort and validated the score in two independent subcohorts. Result(s): In the training sub-cohort (n=667, 56% female), 90% of participants were treated as outpatients for acute COVID-19. Neurological ailments (61.5%) and fatigue (57.1%) persisted most frequently. Across all sub-cohorts, higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index, all p<0.001). Similarly, participants with a higher PCS score consistently showed increased blood inflammatory markers and Ddimer as well as lower diffusing capacity in lung function (all p<0.01). Significant early predictors of the PCS score included the number and intensity of acute symptoms, resilience, and general anxiousness. Conclusion(s): PCS severity can be quantified by an easy-to-use score summarising individual disease burden and reflecting pathological processes. The PCS score promises to facilitate diagnosis of PCS, studies of its natural course, and of therapeutic interventions.
ABSTRACT
COVID-19 convalescents often experience persistent symptoms such as fatigue, neurologic complications or dyspnea, often referred to as "long COVID". To elucidate molecular mechanisms underlying ongoing dyspnea in COVID-19 convalescents, we analyzed single-cell RNA sequencing data from nasal swabs collected during acute infection, and three, six and twelve months post infection together with matching healthy controls. Patients with and without persisting symptoms and with varying severity during the acute phase were included. Post infection, we observed a time-dependent decrease in immune cells. Transcriptional analysis of nasal epithelial cells provided evidence of an impaired cilia assembly, organization and function in COVID-19 convalescents with dyspnea compared to healthy controls and convalescents without ongoing respiratory symptoms. Moreover, differences in the differentiation trajectories of ciliated cells were evident between patients with and without dyspnea, with less diverse differentiation endpoints in the dyspnea patients than in healthy controls or convalescents without respiratory impairment. Overall, our analyses revealed a potential deficiency of ciliated cells in COVID-19 convalescents with dyspnea compared to convalescents without ongoing respiratory symptoms or compared with healthy controls. Ciliated cells clear the lung from particles and mucus. If these cells are functionally impaired, pathogens remain in the airways, causing respiratory problems and infections. Thus, it is reasonable to assume, that impaired ciliated cell function contributes to the persistent respiratory symptoms seen in COVID-19 convalescents.
ABSTRACT
Background: Adrenal insufficiency (AI) is a rare condition caused by an inadequate production of glucocorticoids. Preliminary data in adults suggest that AI could be associated with an increased susceptibility to infections;moreover, AI patients are at risk to develop a severe course of infectious diseases and to experience a life-threatening adrenal crisis. The aim of our study is to evaluate the severity and the outcome of COVID-19 in pediatric AI patients in comparison to subjects affected with other endocrinopathies not involving adrenal gland. Patients and Methods: This was a retrospective, multicenter study involving 11 Italian tertiary-centers of pediatric endocrinology. Data regarding symptoms, severity and duration of the disease, the need to increase the dose or receive parenteral administration of hydrocortisone and the outcome were collected through a telephone interview and review of patient's medical files. From March 2020 to October 2021, 80 children with a history of COVID-19 were collected: 49 subjects affected by AI (42 primary AI, 7 central AI) and 31 subjects as controls. Result(s): Mean age was comparable between patients and controls (11.4+/-4.4 years vs 10+/-3.5 years, respectively). The frequency of signs/symptoms during COVID-19 in AI patients was as follows: fever 68%, rhinorrhea 34%, headache 34%, sore-throat 30%, cough 28%, anosmia/ageusia 21%. Less common symptoms were characterized by arthralgia, abdominal pain, diarrhea and vomiting. The severity of infection was comparable between patients and controls: paucisymptomatic 40.8% vs 25.8%;mild 55.1% vs 61.3%;severe 4.1% vs 12.9%, respectively (Chi-square=0.19). Time between the first positive nasopharyngeal swab and the first negative one in patients vs controls was: <=15 days, 39% vs 56.6%;>15 days, 61% vs 43.3%, showing a tendency to longer infection in AI children, although this difference did not reach statistical significance (Chi-square=0.14). In 64% of AI patients the dose of hydrocortisone was increased during the infection and in 6.4% parenteral hydrocortisone was needed. 94% of AI subjects did not require hospitalization while only 6% were hospitalized with a complete recovery in 100% of cases. Within the entire cohort of AI subjects, 2 children (4%) experienced an adrenal crisis during infection. No fatal events occurred. Conclusion(s): Our data, suggest that children with AI adequately treated are not at increased risk of severe course of COVID-19. In comparison to controls, subjects with AI have a slightly longer duration of the disease, although this data need to be confirmed on larger sample of patients.
ABSTRACT
PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).