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

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.

Targeted Screening for Chronic Q Fever, the Netherlands.

Early detection of and treatment for chronic Q fever might prevent potentially life-threatening complications. We performed a chronic Q fever screening program in general practitioner practices in the Netherlands 10 years after a large Q fever outbreak. Thirteen general practitioner practices located in outbreak areas selected 3,419 patients who had specific underlying medical conditions, of whom 1,642 (48%) participated. Immunofluorescence assay of serum showed that 289 (18%) of 1,642 participants had a previous Coxiella burnetii infection (IgG II titer >1:64), and 9 patients were suspected of having chronic Q fever (IgG I y titer >1:512). After medical evaluation, 4 of those patients received a chronic Q fever diagnosis. The cost of screening was higher than estimated earlier, but the program was still cost-effective in certain high risk groups. Years after a large Q fever outbreak, targeted screening still detected patients with chronic Q fever and is estimated to be cost-effective.

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

[This corrects the article DOI: 10.3389/fimmu.2022.817876.].

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.

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.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory. Methods: To determine whether a memory T cell response is being developed, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker analyses of peripheral blood samples from unvaccinated children and adults with mild-to-moderate COVID-19. Results: 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 several cases 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. Conclusions: Our data indicate that an antigen-specific T cell and antibody response is developed after mild SARS-CoV-2 infection in children and adults. It remains to be elucidated to what extent this SARS-CoV-2-specific response can contribute to an effective recall response after reinfection.

High Infection Secondary Attack Rates of Severe Acute Respiratory Syndrome Coronavirus 2 in Dutch Households Revealed by Dense Sampling.

BACKGROUND: Indoor environments are considered one of the main settings for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Households in particular represent a close-contact environment with high probability of transmission between persons of different ages and roles in society. METHODS: Households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands (March-May 2020) were included. At least 3 home visits were performed during 4-6 weeks of follow-up, collecting naso- and oropharyngeal swabs, oral fluid, feces and blood samples from all household members for molecular and serological analyses. Symptoms were recorded from 2 weeks before the first visit through to the final visit. Infection secondary attack rates (SAR) were estimated with logistic regression. A transmission model was used to assess household transmission routes. RESULTS: A total of 55 households with 187 household contacts were included. In 17 households no transmission took place; in 11 households all persons were infected. Estimated infection SARs were high, ranging from 35% (95% confidence interval [CI], 24%-46%) in children to 51% (95% CI, 39%-63%) in adults. Estimated transmission rates in the household were high, with reduced susceptibility of children compared with adolescents and adults (0.67; 95% CI, .40-1.1). CONCLUSION: Estimated infection SARs were higher than reported in earlier household studies, presumably owing to our dense sampling protocol. Children were shown to be less susceptible than adults, but the estimated infection SAR in children was still high. Our results reinforce the role of households as one of the main multipliers of SARS-CoV-2 infection in the population.

[The role of children in the transmission of SARS-CoV-2]. / De rol van kinderen in de transmissie van SARS-CoV-2.

OBJECTIVE: To determine whether children play a role in the transmission of SARS-CoV-2 to other children and adults, and to gain insight into symptomatic and asymptomatic infections in children. DESIGN: Analysis of national COVID-19 notifications and prospective observational study in families with children. METHOD: Information about COVID-19 patients and their contacts was obtained from the registration systems used by the public health services. In an ongoing study, patients with COVID-19 were asked to participate if they have a family with children. On two occasions nose-throat swabs and blood were collected for PCR analysis and determination of antibodies against SARS-CoV-2. RESULTS: The notifications suggest that transmission finds place mainly between adults and to a lesser extent between parents and children. For the family study, data were available from 54 households with a total of 227 participants. In families of a confirmed COVID-19 patient, children between 1 and 11 years were less often positive in PCR and serology than older children and adults. CONCLUSION: The study gives no indications that children play an important role in the transmission of SARS-CoV-2. Children can indeed become infected, but transmission mainly takes place between adult peers and from adult family members to children. Transmission among children or from children to adults, as is known in influenza, appears to be less common. Ongoing studies should provide important information for further decision-making on control measures, such as closure of schools.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Media Reports as a Source for Monitoring Impact of Influenza on Hospital Care: Qualitative Content Analysis.

BACKGROUND: The Netherlands, like most European countries, has a robust influenza surveillance system in primary care. However, there is a lack of real-time nationally representative data on hospital admissions for complications of influenza. Anecdotal information about hospital capacity problems during influenza epidemics can, therefore, not be substantiated. OBJECTIVE: The aim of this study was to assess whether media reports could provide relevant information for estimating the impact of influenza on hospital capacity, in the absence of hospital surveillance data. METHODS: Dutch news articles on influenza in hospitals during the influenza season (week 40 of 2017 until week 20 of 2018) were searched in a Web-based media monitoring program (Coosto). Trends in the number of weekly articles were compared with trends in 5 different influenza surveillance systems. A content analysis was performed on a selection of news articles, and information on the hospital, department, problem, and preventive or response measures was collected. RESULTS: The trend in weekly news articles correlated significantly with the trends in all 5 surveillance systems, including severe acute respiratory infections (SARI) surveillance. However, the peak in all 5 surveillance systems preceded the peak in news articles. Content analysis showed hospitals (N=69) had major capacity problems (46/69, 67%), resulting in admission stops (9/46, 20%), postponement of nonurgent surgical procedures (29/46, 63%), or both (8/46, 17%). Only few hospitals reported the use of point-of-care testing (5/69, 7%) or a separate influenza ward (3/69, 4%) to accelerate clinical management, but most resorted to ad hoc crisis management (34/69, 49%). CONCLUSIONS: Media reports showed that the 2017/2018 influenza epidemic caused serious problems in hospitals throughout the country. However, because of the time lag in media reporting, it is not a suitable alternative for near real-time SARI surveillance. A robust SARI surveillance program is important to inform decision making.

Explaining the long-term impact of chronic Q fever and Q fever fatigue syndrome on psychosocial functioning: A comparison with diabetes and the general population.

OBJECTIVE: After Q fever infection, 1-5% of patients develop chronic Q fever, while about 20% develops Q fever fatigue syndrome (QFS). This study examines whether these two conditions have a long-term impact on psychosocial functioning compared to the general population and patients with type 2 diabetes (DM) and investigate which mediating factors influence outcomes. METHODS: Cross-sectional study was performed, measuring psychosocial functioning including quality of life (depression and satisfaction with life), anxiety, social functioning and relationship satisfaction in patients with proven or probable chronic Q fever or QFS, 5-9 years after acute Q fever infection. Multivariate linear regression was used to analyse differences between groups, correct for confounders and identify relevant mediators (fatigue, physical or cognitive functioning, illness perception). RESULTS: Quality of life and social functioning of chronic Q-fever and QFS patients was significantly lower and anxiety significantly higher compared to DM patients and the general population. The impact was completely mediated by fatigue in both Q fever groups. Physical and cognitive functioning and illness perception partially mediated the impact. CONCLUSIONS: Health care workers need to be aware of the long-term impact of chronic Q fever and QFS on psychosocial functioning of patients in order to provide proper guidance.