Neuropsychological functioning after COVID-19: minor differences between individuals with and without persistent complaints after SARS-CoV-2 infection.

Objective: It is unclear how self-reported severe fatigue and difficulty concentrating after SARS-CoV-2 infection relate to objective neuropsychological functioning. The study aimed to compare neuropsychological functioning between individuals with and without these persistent subjective complaints. Method: Individuals with and without persistent severe fatigue (Checklist Individual Strength (CIS) fatigue ≥ 35) and difficulty concentrating (CIS concentration ≥ 18) at least 3 months after SARS-CoV-2 infection were included. Neuropsychological assessment was performed on overall cognitive functioning, attention, processing speed, executive functioning, memory, visuo-construction, and language (18 tests). T-scores -1.5 SD below population normative data (T ≤ 35) were classified as "impaired". Results: 230 participants were included in the study, of whom 22 were excluded from the analysis due to invalid performance. Of the participants included in the analysis, 111 reported persistent complaints of severe fatigue and difficulty concentrating and 97 did not. Median age was 54 years, 59% (n = 126) were female, and participants were assessed a median of 23 months after first infection (IQR: 16-28). With bivariate logistic regression, individuals with persistent complaints had an increased likelihood of slower information processing speed performance on the Stroop word reading (OR = 2.45, 95%CI = 1.02-5.84) compared to those without persistent complaints. Demographic or clinical covariates (e.g. hospitalization) did not influence this association. With linear regression techniques, persistent complaints were associated with lower t-scores on the D2 CP, TMT B, and TMT B|A. There were no differences in performance on the other neuropsychological tests. Conclusions: Individuals with subjective severe fatigue and difficulty concentrating after COVID-19 do not typically demonstrate cognitive impairment on extensive neuropsychological testing.

Neurobiological basis and risk factors of persistent fatigue and concentration problems after COVID-19: study protocol for a prospective case-control study (VeCosCO).

INTRODUCTION: The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation, could be the underlying pathophysiological mechanism for persisting complaints.To unravel factors associated with persisting complaints, VeCosCO will compare individuals with and without persistent fatigue and cognitive complaints >3 months after infection with SARS-CoV-2. The study consists of two work packages. The first work package aims to (1) investigate the relation between persisting complaints and neuropsychological functioning; (2) determine risk factors and at-risk phenotypes for the development of persistent fatigue and cognitive complaints, including the presence of postexertional malaise and (3) describe consequences of persistent complaints on quality of life, healthcare consumption and physical functioning. The second work package aims to (1) determine the presence of neuroinflammation with [18F]DPA-714 whole-body positron emission tomography (PET) scans in patients with persisting complaints and (2) explore the relationship between (neuro)inflammation and brain structure and functioning measured with MRI. METHODS AND ANALYSIS: This is a prospective case-control study in participants with and without persistent fatigue and cognitive complaints, >3 months after laboratory-confirmed SARS-CoV-2 infection. Participants will be mainly included from existing COVID-19 cohorts in the Netherlands covering the full spectrum of COVID-19 acute disease severity. Primary outcomes are neuropsychological functioning, postexertional malaise, neuroinflammation measured using [18F]DPA-714 PET, and brain functioning and structure using (f)MRI. ETHICS AND DISSEMINATION: Work package 1 (NL79575.018.21) and 2 (NL77033.029.21) were approved by the medical ethical review board of the Amsterdam University Medical Centers (The Netherlands). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in peer-reviewed journals and shared with the key population.

Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19.

Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis.

In-depth Characterization of Vaccine Breakthrough Infections With SARS-CoV-2 Among Health Care Workers in a Dutch Academic Medical Center.

Severe acute respiratory syndrome coronavirus 2 infection after coronavirus disease 2019 vaccination raises concerns about the emergence of vaccine escape variants. Here we characterize 14 breakthrough infections among 5860 fully vaccinated Dutch health care workers ≥14 days after the final dose of vaccination with either BNT162b2, mRNA-1273, or Ad26.COV2.S. These breakthrough infections presented with regular B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants and high viral loads, despite normal vaccine-induced B- and T-cell immune responses detected by live virus neutralization assays and ELISpot. High-risk exposure settings, such as in households, indicate a potential risk of viral transmission despite full vaccination.