Delineating immune variation between adult and children COVID-19 cases and associations with disease severity

Abstract The SARS-CoV-2 pandemic has emphasized the need to explore how variations in the immune system relate to the severity of the disease. This study aimed to explore inter-individual variation in response to SARS-CoV-2 infection by comparing T cell, B cell, and innate cell immune subsets among primary infected children and adults (i.e., those who had never experienced SARS-CoV-2 infection nor received vaccination previously), with varying disease severity after infection. We also examined immune subset kinetics in convalescent individuals compared to those with persistent infection to identify possible markers of immune dysfunction. Distinct immune subset differences were observed between infected adults and children, as well as among adult cases with mild, moderate, and severe disease. IgM memory B cells were absent in moderate and severe cases whereas frequencies of B cells with a lack of surface immunoglobulin expression were significantly higher in severe cases. Interestingly, these immune subsets remained stable during recovery implying that these subsets could be associated with underlying baseline immune variation. Our results offer insights into the potential immune markers associated with severe COVID-19 and provide a foundation for future research in this area

Objective cognitive performance and subjective complaints in patients with chronic Q fever or Q fever fatigue syndrome.

Primary aim of this study was to compare cognitive performance of patients with chronic Q fever or Q fever fatigue syndrome (QFS) to matched controls from the general population, while taking performance validity into account. Second, we investigated whether objective cognitive performance was related to subjective cognitive complaints or psychological wellbeing. Cognitive functioning was assessed with a neuropsychological test battery measuring the domains of processing speed, episodic memory, working memory and executive functioning. Tests for performance validity and premorbid intelligence were also included. Validated questionnaires were administered to assess self-reported fatigue, depressive symptoms and cognitive complaints. In total, 30 patients with chronic Q fever, 32 with QFS and 35 controls were included. A high percentage of chronic Q fever patients showed poor performance validity (38%) compared to controls (14%, p = 0.066). After exclusion of participants showing poor performance validity, no significant differences between patients and controls were found in the cognitive domains. QFS patients reported a high level of cognitive complaints compared to controls (41.2 vs 30.4, p = 0.023). Cognitive complaints were not significantly related to cognitive performance in any of the domains for this patient group. The high level of self-reported cognitive complaints in QFS patients does not indicate cognitive impairment. A large proportion of the chronic Q fever patients showed suboptimal mental effort during neuropsychological assessment. More research into the underlying explanations is needed. Our findings stress the importance of assessing cognitive functioning by neuropsychological examination including performance validity, rather than only measuring subjective cognitive complaints

Impact of Q-fever fatigue syndrome on patients' work status.

BACKGROUND: Chronic illnesses can increase the risk of unemployment, but evidence on the specific impact of Q-fever fatigue syndrome (QFS) on work is lacking. AIMS: The aim of this study was to describe and quantify the impact of QFS on work. METHODS: Changes in work status from 1 year prior to 4 years after acute Q-fever infection of QFS patients were retrospectively collected with a self-report questionnaire measuring employment status and hours of paid work per week. In addition, information on work ability, job satisfaction and need for recovery after work was collected in 2016. Data were compared to participants from the general population. RESULTS: The proportion of employed QFS patients from 1 year prior to 4 years after acute infection decreased from 78 to 41%, while remaining relatively constant in the general population (82 to 78%). Working QFS patients showed a decrease in mean hours of paid work from 35 to 22 h per week, which is significantly steeper compared to the general population (31-28 h per week) (P < 0.001). QFS patients showed a significantly lower work ability (P < 0.001), lower job satisfaction (P = 0.006) and greater need for recovery (P < 0.001) compared to the general population. CONCLUSIONS: The number of QFS patients with paid work decreased over the years, while patients who continue to work experience lower work ability, job satisfaction and increased need for recovery. Occupational physicians should be aware of the occurrence and severity of the impact of QFS on work, even after many years

Impact of Q-fever on physical and psychosocial functioning until 8 years after Coxiella burnetii infection: An integrative data analysis.

BACKGROUND: This study aimed to determine short- and long-term physical and psychosocial impact of Coxiella burnetii infection in three distinct entities: Q-fever fatigue syndrome (QFS), chronic Q-fever, and patients with past acute Q-fever without QFS or chronic Q-fever. METHODS: Integrative data analysis was performed, combining original data from eight studies measuring quality of life (QoL), fatigue, physical and social functioning with identical validated questionnaires, from three months to eight years after onset infection. Linear trends in each outcome were compared between Q-fever groups using multilevel linear regression analyses to account for repeated measures within patients. RESULTS: Data included 3947 observations of 2313 individual patients (228 QFS, 135 chronic Q-fever and 1950 patients with past acute Q-fever). In the first years following infection, physical and psychosocial impact was highest among QFS patients, and remained high without significant improvements over time. In chronic Q-fever patients, QoL and physical functioning worsened significantly over time. Levels of fatigue and social participation in patients with past acute Q-fever improved significantly over time. CONCLUSION: The impact differs greatly between the three Q-fever groups. It is important that physicians are aware of these differences, in order to provide relevant care for each patient group

Children and Adults With Mild COVID-19: Dynamics of the Memory T Cell Response up to 10 Months.

Upon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-γ T cell responses in infected children (83%) and adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially in those with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-γ T cell response correlated with S1-SARS-CoV-2-specific serum antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens. Frequencies of SARS-CoV-2-specific T cells were significantly reduced at 10 months after symptom onset, while S1-SARS-CoV-2-specific IgG concentrations were still detectable in 90% of all children and adults

SARS-CoV-2 RNA and antibody dynamics in a Dutch household study with dense sampling frame.

This study investigated the dynamics of SARS-CoV-2 infection and diagnostics in 242 household members of different ages and with different symptom severity after SARS-CoV-2 exposure early in the pandemic (March–April 2020). Households with a SARS-CoV-2 confirmed positive case and at least one child in the Netherlands were followed for 6 weeks. Naso (NP)- and oropharyngeal (OP) swabs, oral fluid and feces specimens were analyzed for SARS-CoV-2 RNA and serum for SARS-CoV-2-specific antibodies. The dynamics of the presence of viral RNA and the serological response was modeled to determine the sampling time-frame and sample type with the highest sensitivity to confirm or reject a SARS-CoV-2 diagnosis. In children higher viral loads compared to adults were detected at symptom onset. Early in infection, higher viral loads were detected in NP and OP specimens, while RNA in especially feces were longer detectable. SARS-CoV-2-specific antibodies have 90% probability of detection from 7 days (total Ig) and 18 days (IgG) since symptom onset. For highest probability of detection in SARS-CoV-2 diagnostics early in infection, RT-PCR on NP and OP specimens are more sensitive than on oral fluid and feces. For SARS-CoV-2 diagnostics late after infection, RT-PCR on feces specimens and serology are more valuable