Prevalence and predictors of long COVID among non-hospitalised adolescents and young adults: a prospective controlled cohort study (preprint)

The prevalence and predictors of long COVID in young people remain unresolved. We aimed to determine the point prevalence of long COVID in non-hospitalised adolescents and young adults six months after the acute infection, to determine the risk of developing long COVID adjusted for possible confounders, and to explore a broad range of potential risk factors (prespecified outcomes). We conducted a prospective controlled cohort study of 404 SARS-CoV-2-positive and 105 SARS-CoV-2-negative non-hospitalised individuals aged 12–25 years (ClinicalTrial ID: NCT04686734). Data acquisition was completed February 2022. Assessments included pulmonary, cardiac and cognitive functional testing, biomarker analyses, and completion of a questionnaire, and were performed at inclusion (early convalescent stage) and six months follow-up. The WHO case definition of long COVID was applied. The point prevalence of long COVID at six months was 49% and 47% in the SARS-CoV-2-positive and negative group, respectively. SARS-CoV-2-positivity did not predict development of long COVID (relative risk 1.06, 95% CI 0.83 to 1.37). The main predictor was symptom severity at inclusion, which correlated strongly to personality traits. Low physical activity and loneliness were also predictive, while biological markers were not. In conlusion, our study aims were met, and the findings suggest that persistent symptoms were not driven by the infection, but were associated with psychosocial factors.

Serum Neurofilament Light is Elevated in COVID-19 Positive Adults in the ICU and is Associated with Co-Morbid Cardiovascular Disease, Neurological Complications, and Acuity of Illness (preprint)

In critically ill COVID-19 patients, the risk of long-term neurological consequences is just beginning to be appreciated. While recent studies have identified that there is an increase in structural injury to the nervous system in critically ill COVID-19 patients, there is little known about the relationship of COVID-19 neurological damage to the systemic inflammatory diseases also observed in COVID-19 patients. The purpose of this pilot observational study was to examine the relationships between serum neurofilament light protein (NfL, a measure of neuronal injury) and co-morbid cardiovascular disease (CVD) and neurological complications in COVID-19 positive patients admitted to the intensive care unit (ICU). In this observational study of one-hundred patients who were admitted to the ICU in Tucson, Arizona between April and August 2020, 89 were positive for COVID-19 (COVID-pos) and 11 were COVID-negative (COVID-neg). A healthy control group (n=8) was examined for comparison. The primary outcomes and measures were subject demographics, serum NfL, presence and extent of CVD, diabetes, sequential organ failure assessment score (SOFA), presence of neurological complications, and blood chemistry panel data. COVID-pos patients in the ICU had significantly higher mean levels of Nfl (229.6+163 pg/ml) compared to COVID-neg ICU patients (19.3+5.6 pg/ml), Welchs t-test, p =.01 and healthy controls (12.3+3.1 pg/ml), Welchs t-test p =.005. Levels of Nfl in COVID-pos ICU patients were significantly higher in patients with concomitant CVD and diabetes (n=35, log Nfl 1.6+.09), and correlated with higher SOFA scores (r=.5, p =.001). These findings suggest that in severe COVID-19 disease, the central neuronal and axonal damage in these patients may be driven, in part, by the level of systemic cardiovascular disease and peripheral inflammation. Understanding the contributions of systemic inflammatory disease to central neurological degeneration in these COVID-19 survivors will be important to the design of interventional therapies to prevent long-term neurological and cognitive dysfunction.

Critical Illness Polyneuropathy and Myopathy in COVID-19 Patients: A Prospective Observational Intensive Care Unit Cross-Sectional Cohort Study (preprint)

Background: Several reports on neurological complications associated with SARS-CoV-2 infection have been published. However, systematic description on intensive care unit acquired weakness (ICUAW) are still missing. Methods: The objective was to determine the incidence and characteristics of critical illness polyneuropathy (CIN) and myopathy (CIM) in patients with severe COVID-19. We also aimed to describe the electrophysiological features and their relation to plasma biomarkers for neuronal injury. This was a prospective observational intensive care unit cohort study. All adult patients admitted to the general intensive care unit (ICU) at Uppsala University Hospital, Uppsala, Sweden, between March 13 and June 8, 2020 were screened for inclusion. Patients with PCR confirmed COVID-19 were included. All patients were admitted to intensive care treatment due to severe COVID-19, including intravenous anaesthesia, opioid anaelgesia, neuromuscular blockade and mechanical ventilation. Associations of clinical, electrophysiological (sensory and motor conduction studies and electromyography) and biomarker data [neurofilament light chain (NfL), glial fibrillary acidic protein (GFAp) and tau] were studied between COVID-19 patients who developed CIN/CIM and those who did not. Results: 111 COVID-19 patients were included, 11 (11 males, mean age: 64 years) developed CIN/CIM whereas 100 (74 males, mean age: 61 years) did not (non-CIN/CIM). The CIN/CIM incidence was higher in COVID-19 patients compared to a general ICU-population treated during 2019 (9.9% vs 3.4%). In particular CIN was more frequent in the COVID-19 ICU cohort (50%) compared with the non-COVID-19 ICU cohort (0%, p=0.008). NfL and GFAp levels were higher in the CIN/CIM group both at the early (<9 days) and late time points (>11 days) compared with the non-CIN/CIM group (both p=0.001) and correlated with nerve amplitudes. Conclusions: CIN/CIM, in particular CIN, were more prevalent among COVID-19 patients than an ICU treated control cohort and should be considered in the differential diagnostic workup and the further rehabilitation of COVID-19 patients. COVID-19 patients who later developed ICUAW had significantly higher NfL and GFAp in the early phase of ICU care, which suggests their potential as predictive biomarkers. Trial registration: The study protocol was registered (ClinicalTrialsID:NCT04316884). Mechanisms for Organ Dysfunction in Covid-19 (UMODCOVID19) March 18, 2020.

Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19 (preprint)

ObjectiveTo test the hypotheses that blood concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. MethodsForty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa). Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. ResultsIn total, 21 % (n = 10) of the patients were admitted to an intensive care unit, whereas the overall mortality rate was 13 % (n = 6). Non-survivors had higher serum concentrations of NfL than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10-7) and unadjusted analyses (p = 0.001). Serum concentrations of GFAp were significantly higher in non-survivors than survivors in adjusted analyses (p = 0.02). The NfL concentrations in non-survivors increased over repeated measurements, whereas the concentrations in survivors were stable. Significantly higher concentrations of NfL were found in patients reporting fatigue, while reduced concentrations were found in patients experiencing cough, myalgia and joint pain. ConclusionIncreased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.

Proteomic blood profiling in mild, severe and critical COVID-19 patients (preprint)

The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in the majority of individuals leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. The purpose of this study is to explore the proteomic differences between mild, severe and critical COVID-19 positive patients. Blood protein profiling was performed on 59 COVID-19 mild (n=26), severe (n=9) or critical (n=24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/. Our results demonstrate that dynamic changes in blood proteins that associate with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.

Steroid-responsive severe encephalopathy in SARS-CoV-2 infection (preprint)

SARS-CoV-2 infection has the potential for targeting central nervous system and several neurological symptoms have been described in patients with severe respiratory distress. Here we described the case of an otherwise healthy 60-year old subject with SARS-CoV-2 infection but only mild respiratory abnormalities who developed severe progressive encephalopathy associated with mild pleocytosis and hyperproteinorrachia. MRI was negative whereas EEG showed theta waves on the anterior brain regions. Serum and CSF analyses excluded other known infectious or autoimmune disorders. The patient dramatically improved after high-doses steroid treatment suggesting an inflammatory-mediated brain involvement related to SARS-CoV-2 infection