Laboratory parameters related to disease severity and physical performance after reconvalescence of acute COVID-19 infection.

Research into the molecular basis of disease trajectory and Long-COVID is important to get insights toward underlying pathophysiological processes. The objective of this study was to investigate inflammation-mediated changes of metabolism in patients with acute COVID-19 infection and throughout a one-year follow up period. The study enrolled 34 patients with moderate to severe COVID-19 infection admitted to the University Clinic of Innsbruck in early 2020. The dynamics of multiple laboratory parameters (including inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), neopterin] as well as amino acids [tryptophan (Trp), phenylalanine (Phe) and tyrosine (Tyr)], and parameters of iron and vitamin B metabolism) was related to disease severity and patients' physical performance. Also, symptom load during acute illness and at approximately 60 days (FU1), and one year after symptom onset (FU2) were monitored and related with changes of the investigated laboratory parameters: During acute infection many investigated laboratory parameters were elevated (e.g., inflammatory markers, ferritin, kynurenine, phenylalanine) and enhanced tryptophan catabolism and phenylalanine accumulation were found. At FU2 nearly all laboratory markers had declined back to reference ranges. However, kynurenine/tryptophan ratio (Kyn/Trp) and the phenylalanine/tyrosine ratio (Phe/Tyr) were still exceeding the 95th percentile of healthy controls in about two thirds of our cohort at FU2. Lower tryptophan concentrations were associated with B vitamin availability (during acute infection and at FU1), patients with lower vitamin B12 levels at FU1 had a prolonged and more severe impairment of their physical functioning ability. Patients who had fully recovered (ECOG 0) presented with higher concentrations of iron parameters (ferritin, hepcidin, transferrin) and amino acids (phenylalanine, tyrosine) at FU2 compared to patients with restricted ability to work. Persistent symptoms at FU2 were tendentially associated with IFN-γ related parameters. Women were affected by long-term symptoms more frequently. Conclusively, inflammation-mediated biochemical changes appear to be related to symptoms of patients with acute and Long Covid.

Body Composition and Physical Performance 1 Year After COVID-19.

OBJECTIVE: Long-term consequences after COVID-19 include physical complaints, which may impair physical recovery and quality of life. DESIGN: We assessed body composition and physical ability in patients 12 months after COVID-19. Consecutively recruited patients recovering from mild to severe COVID-19 were assessed using bioelectrical impedance analysis, 6-min-walk test, additional scales for physical performance and health-related quality of life. RESULTS: Overall physical recovery was good (i.e., Glasgow Outcome Scale-Extended ≥7 in 96%, Modified Rankin Scale ≤1 in 87%, Eastern Cooperative Oncology Group ≤1 in 99%). Forty-four percent of the 69 patients experienced a significant body mass index increase in the year after COVID-19 (≥1 kg/m 2 ), whereas skeletal muscle mass index was reduced in only 12%. Patients requiring intensive care treatment ( n = 15, 22%) during acute COVID-19 more often had a body mass index increase ( P = 0.002), worse 6-min-walk test-performance ( P = 0.044), and higher body fat mass ( P = 0.030) at the 1-yr follow-up when compared with patients with mild ( n = 22, 32%) and moderate ( n = 32, 46%) acute COVID-19. Body mass index increase was also more frequent in patients who had no professional rehabilitation ( P = 0.014). CONCLUSIONS: Although patients with severe COVID-19 had increased body mass index and body fat and performed worse in physical outcome measures 1 yr after COVID-19, overall physical recovery was satisfying. Translating these findings to variants beyond the Alpha strain of severe acute respiratory syndrome coronavirus 2 virus needs further studies.

Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae.

PURPOSE: Olfactory dysfunction (OD) commonly accompanies coronavirus disease 2019 (COVID-19). We investigated the kinetics of OD resolution following SARS-CoV-2 infection (wild-type and alpha variant) and its impact on quality of life, physical and mental health. METHODS: OD prevalence was assessed in an ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and an observational cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up). Co-occurrence of OD with other symptoms and effects on quality of life, physical and mental health were analyzed by multi-dimensional scaling, association rule mining and semi-supervised clustering. RESULTS: Both in the ambulatory COVID-19 survey study (72%) and the observational ambulatory and hospitalized cohort (41%) self-reported OD was frequent during acute COVID-19. Recovery from self-reported OD was slow (survey: median 28 days, observational cohort: 90 days). By clustering of the survey data, we identified a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorders (median recovery: 90 days) but low frequency of post-acute fatigue, respiratory or neurocognitive symptoms. This smell and taste disorder cluster was characterized by a high rating of physical performance, mental health, and quality of life as compared with convalescents affected by prolonged fatigue or neurocognitive complaints. CONCLUSION: Our results underline the heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype is characterized by good clinical, physical, and mental recovery and may pose a minor challenge for public health. STUDY REGISTRATION: ClinicalTrials.gov: NCT04661462 (survey study), NCT04416100 (observational cohort).

The Impact of Iron Dyshomeostasis and Anaemia on Long-Term Pulmonary Recovery and Persisting Symptom Burden after COVID-19: A Prospective Observational Cohort Study.

Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort study "Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (CovILD)" encompasses serial extensive clinical, laboratory, functional and imaging evaluations at 60, 100, 180 and 360 days after COVID-19 onset. We included 108 individuals with mild-to-critical acute COVID-19, whereas 75% presented with severe acute disease. At 60 days post-COVID-19 follow-up, hyperferritinaemia (35% of patients), iron deficiency (24% of the cohort) and anaemia (9% of the patients) were frequently found. Anaemia of inflammation (AI) was the predominant feature at early post-acute follow-up, whereas the anaemia phenotype shifted towards iron deficiency anaemia (IDA) and combinations of IDA and AI until the 360 days follow-up. The prevalence of anaemia significantly decreased over time, but iron dyshomeostasis remained a frequent finding throughout the study. Neither iron dyshomeostasis nor anaemia were related to persisting structural lung impairment, but both were associated with impaired stress resilience at long-term COVID-19 follow-up. To conclude, iron dyshomeostasis and anaemia are frequent findings after COVID-19 and may contribute to its long-term symptomatic outcome.

Chest CT of Lung Injury 1 Year after COVID-19 Pneumonia: The CovILD Study.

Background The long-term pulmonary sequelae of COVID-19 is not well known. Purpose To characterize patterns and rates of improvement of chest CT abnormalities 1 year after COVID-19 pneumonia. Materials and Methods This was a secondary analysis of a prospective, multicenter observational cohort study conducted from April 29 to August 12, 2020, to assess pulmonary abnormalities at chest CT approximately 2, 3, and 6 months and 1 year after onset of COVID-19 symptoms. Pulmonary findings were graded for each lung lobe using a qualitative CT severity score (CTSS) ranging from 0 (normal) to 25 (all lobes involved). The association of demographic and clinical factors with CT abnormalities after 1 year was assessed with logistic regression. The rate of change of the CTSS at follow-up CT was investigated by using the Friedmann test. Results Of 142 enrolled participants, 91 underwent a 1-year follow-up CT examination and were included in the analysis (mean age, 59 years ± 13 [SD]; 35 women [38%]). In 49 of 91 (54%) participants, CT abnormalities were observed: 31 of 91 (34%) participants showed subtle subpleural reticulation, ground-glass opacities, or both, and 18 of 91 (20%) participants had extensive ground-glass opacities, reticulations, bronchial dilation, microcystic changes, or a combination thereof. At multivariable analysis, age of more than 60 years (odds ratio [OR], 5.8; 95% CI: 1.7, 24; P = .009), critical COVID-19 severity (OR, 29; 95% CI: 4.8, 280; P < .001), and male sex (OR, 8.9; 95% CI: 2.6, 36; P < .001) were associated with persistent CT abnormalities at 1-year follow-up. Reduction of CTSS was observed in participants at subsequent follow-up CT (P < .001); during the study period, 49% (69 of 142) of participants had complete resolution of CT abnormalities. Thirty-one of 49 (63%) participants with CT abnormalities showed no further improvement after 6 months. Conclusion Long-term CT abnormalities were common 1 year after COVID-19 pneumonia. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leung in this issue.

Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients' performance: a prospective observational cohort study.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology. METHODS: We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing. RESULTS: We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia. DISCUSSION: Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04416100.