Validation of dried blood spot sampling for detecting SARS-CoV-2 antibodies and total immunoglobulins in a large cohort of asymptomatic young adults.

BACKGROUND: Detecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. METHODS: We compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. RESULTS: Baseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. CONCLUSIONS: This is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.

Chronic Adolescent Social Instability Stress Leads to Impaired Recognition Memory and Increased Hippocampal FKBP5 and CRHR2 Expression in Adulthood

Background: Recently published studies indicate that the Covid-19 pandemic has dramatically increased rates of anxiety, depression, and suicide in adolescents and young adults. Human and animal studies strongly indicate that early life stress leads to lasting changes to cognition and psychiatric outcomes, but less is known about how chronic adolescent stress may alter brain function across the lifespan. Methods: The current study examines the effects of chronic social instability stress (SIS) on male and female mice from 4 to 11 weeks of age. SIS mice (n=52) experienced twice weekly cage changes, preventing the formation of stable social hierarchies, while control mice (n=48) remained with their original cage mates. Mice were subsequently assessed throughout adulthood for changes in behavior associated with anxiety, affect, aggression, motivation, and recognition memory. At 66 weeks of age, levels hippocampal mRNA expression of genes associated with human early life stress were also compared (CRHR1, CRHR2, FKBP5, SLCA4). Results: Mice exposed to SIS showed decreased novel object recognition (p=0.002) and responded more during the progressive ratio task (p=0.033). At 66 weeks, SIS mice had increased hippocampal FKBP5 (p=0.03) and CRHR2 (p=0.005) expression relative to controls;furthermore, these measures negatively correlated with novel object recognition (FKBP: p=0.007;CRHR2: p=0.04). Conclusions: Chronic adolescent social instability stress led to persistent memory deficits and increased hedonic seeking in adulthood, possibly due to hippocampal damage resultant from lasting alterations to the stress cascade. Future studies will determine the cellular, molecular and circuit-level changes underlying these effects. Supported By: Support from an institutional grant from USC department of Psychiatry and Keck School of Medicine Keywords: Early Life Stress, FKBP5, Memory Deficit

We're Not Gonna Fall: Depressive Complaints, Personal Resilience, Team Social Climate, and Worries about Infections among Hospital Workers during a Pandemic

Maintaining hospital workers' psychological health is essential for hospitals' capacities to sustain organizational functioning during the COVID-19 pandemic. Workers' personal resilience can be an important factor in preserving psychological health, but how this exactly works in high stakes situations, such as the COVID-19 pandemic, requires further exploration. Similarly, the role of team social climate as contributor to individual psychological health seems obvious, but how it exactly prevents workers from developing depressive complaints in prolonged crises remains under investigated. The present paper therefore applies conservation of resources theory to study the relationships between resilience, team social climate, and depressive complaints, specifically focusing on worries about infections as an important explanatory mechanism. Based on questionnaire data of 1126 workers from five hospitals in the Netherlands during the second peak of the pandemic, this paper estimates a moderated-mediation model. This model shows that personal resilience negatively relates to depressive complaints (beta = -0.99, p < 0.001, 95%CI = -1.45--0.53), partially as personal resilience is negatively associated with worries about infections (beta = -0.42, p < 0.001, 95%CI = -0.50--0.33) which in turn are positively related to depressive complaints (beta = 0.75, p < 0.001, 95% CI = 0.31-1.19). Additionally, team social climate is associated with a lower effect of worries about being infected and infecting others on depressive complaints (beta = -0.88, p = 0.03, 95% CI = -1.68--0.09). These findings suggest that resilience can be an important individual level resource in preventing depressive complaints. Moreover, the findings imply that hospitals have an important responsibility to maintain a good team social climate to shield workers from infection related worries building up to depressive complaints.

The use of routine blood tests to assist the diagnosis of COVID-19 in symptomatic hospitalized patients.

INTRODUCTION: Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19. METHOD: A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient's clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation. RESULTS: Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of -0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR. DISCUSSION: Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.

Does vitamin D supplementation prevent SARS-CoV-2 infection in military personnel? Review of the evidence.

For most individuals residing in Northwestern Europe, maintaining replete vitamin D status throughout the year is unlikely without vitamin D supplementation and deficiency remains common. Military studies have investigated the association with vitamin D status, and subsequent supplementation, with the risk of stress fractures particularly during recruit training. The expression of nuclear vitamin D receptors and vitamin D metabolic enzymes in immune cells additionally provides a rationale for the potential role of vitamin D in maintaining immune homeostasis. One particular area of interest has been in the prevention of acute respiratory tract infections (ARTIs). The aims of this review were to consider the evidence of vitamin D supplementation in military populations in the prevention of ARTIs, including SARS-CoV-2 infection and consequent COVID-19 illness. The occupational/organisational importance of reducing transmission of SARS-CoV-2, especially where infected young adults may be asymptomatic, presymptomatic or paucisymptomatic, is also discussed.