Project description:With the recent approval of highly effective coronavirus disease 2019 (COVID-19) vaccines, functional and lasting immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently under investigation as antibody levels in plasma were shown to decline during convalescence. Since the absence of antibodies does not equate to absence of immune memory, we evaluate the presence of SARS-CoV-2-specific memory B cells in convalescent individuals. Here, we report a longitudinal assessment of humoral immune responses on 32 donors up to 8 months post-symptom onset. Our observations indicate that anti-Spike and anti-receptor binding domain (RBD) immunoglobulin M (IgM) in plasma decay rapidly, whereas the reduction of IgG is less prominent. Neutralizing activity also declines rapidly when compared to Fc-effector functions. Concomitantly, the frequencies of RBD-specific IgM+ B cells wane significantly when compared to RBD-specific IgG+ B cells, which remain stable. Our results add to the current understanding of immune memory following SARS-CoV-2 infection, which is critical for secondary infection prevention and vaccine efficacy.
Project description:The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. That non-classical monocytes may be a source of inflammation in PASC warrants further study.
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months.MethodsThe study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus.ResultsAntibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs).ConclusionsCoronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.
Project description:BackgroundSouth Africa is one of the most 'unequal' societies in the world. Despite apartheid ending more than 20 years ago, material inequalities remain interwoven with ethnic/racial inequalities. There is limited research on the prevalence/predictors of common mental disorders (CMD) among young people. Adolescence is a unique time-point during which intervention may lead to improved mental health and reduced social problems later. The study objective was to assess mental health disparities in a representative sample of adolescents growing up in South Africa.MethodsCross-sectional associations of race/ethnicity and material disadvantage with CMD and Post Traumatic Stress Disorder (PTSD) were assessed in a stratified random sample representative of school-attendees, aged 14-15 years, in a large metropolitan area of Cape Town. Validated instruments assessed mental disorders; these included: Harvard Trauma Questionnaire (PTSD); Short Moods and Feelings Questionnaire (depression); Zung self-rated anxiety scale (anxiety). Self-ascribed ethnicity was determined using procedures similar to the South African census and previous national surveys.ResultsResponse rate was 88% (1034 of 1169 individuals). Adolescents experienced a high prevalence of depression (41%), anxiety (16%) and PTSD (21%). A gradient between material disadvantage and CMD/ PTSD was evident across all ethnic/racial groups. Respondents self-identifying as 'black' or 'coloured' were disadvantaged across most indicators. After adjusting for confounders, relative to white children, relative risk (RR) of CMD in black children was 2.27 (95% CI:1.24, 4.15) and for PTSD was RR: 2.21 (95% CI:1.73, 2.83). Relative risk of CMD was elevated in children self-identifying as 'coloured' (RR: 1.73, 95% CI:1.11, 2.70). Putative mediators (violence, racially motivated bullying, social support, self-esteem) partially accounted for differences in CMD and fully for PTSD.ConclusionsAdolescent mental health inequalities in Cape Town are associated with material disadvantage and self-identification with historically disadvantaged groups.
Project description:BackgroundIn South Africa, there are limited data on the burden of diarrhoea at a community level, specifically in older children and adults. This community survey estimated rates of and factors associated with diarrhoea across all ages and determined the proportion of cases presenting to healthcare facilities.MethodsHouseholds were enrolled from an existing urban health and demographic surveillance site. A household representative was interviewed to determine associated factors and occurrence of diarrhoea in the household, for all household members, in the past 2 weeks (including symptoms and health seeking behaviour). Diarrhoeal rate of any severity was calculated for < 5 years, 5-15 years and > 15 years age groups. Factors associated with diarrhoea and health seeking behaviour were investigated using binomial logistic regression.ResultsDiarrhoeal rate among respondents (2.5 episodes/person-year (95% CI, 1.8-3.5)) was significantly higher than for other household members (1.0 episodes/person-year (95% CI, 0.8-1.4); IRR = 2.4 (95% CI, 1.5-3.7) p < 0.001). Diarrhoeal rates were similar between age groups, however younger children (< 5 years) were more likely to present to healthcare facilities than adults (OR = 5.9 (95% CI, 1.1-31.4), p = 0.039). Oral rehydration solution was used in 44.8% of cases. Having a child between 5 and 15 years in the household was associated with diarrhoea (OR = 2.3 (95% CI, 1.3-3.9), p = 0.003) and, while 26.4% of cases sought healthcare, only 4.6% were hospitalised and only 3.4% of cases had a stool specimen collected. While the majority of cases were mild, 13.8% of cases felt they required healthcare but were unable to access it.ConclusionDiarrhoeal rate was high across all age groups in this community; however, older children and adults were less likely to present to healthcare, and are therefore underrepresented through facility-based clinical surveillance. Current diarrhoeal surveillance represents a fraction of the overall cases occurring in the community.
Project description:Nasopharyngeal colonization is the first step in the pathway to Streptococcus pneumoniae (Spn) infection, a leading cause of childhood morbidity and mortality. We investigated the effect of Spn colonization at ages 2 and 4 mo on growth at age 6 mo among 389 infants living in rural South India by using data from an Spn carriage study nested within a randomized, double-blind, placebo-controlled community trial designed to evaluate the impact of newborn vitamin A supplementation on Spn carriage in the first 6 mo of life. Primary outcomes were weight, length, and anthropometric indices of nutritional status. Growth data at age 6 mo were available for 84% (389 of 464) of infants in the Spn carriage study. Carriage at age 2 mo was associated with increased odds of stunting [OR: 3.07 (95% CI: 1.29, 7.36) P = 0.012] and lower weight [β: -266 g (95% CI: -527, -5) P = 0.045], length [β: -1.31 cm (95% CI: -2.32, -0.31) P = 0.010], and length-for-age Z scores [β: -0.59; (95% CI: -1.05, -0.13) P = 0.012] at age 6 mo. Spn carriage at age 4 mo did not affect growth. Carriage of invasive serotypes at age 2 mo was associated with decreases in mean weight [β: -289 g; (95% CI: -491, -106) P = 0.002] and length [β:-0.38 cm (95% CI: -1.49, -0.01) P = 0.047] at age 6 mo. Newborn vitamin A supplementation did not modify the association between Spn carriage and growth. Results suggest that pneumococcal carriage at age 2 mo is an independent risk factor for poor growth in young infants. Future studies need to clarify the role of Spn carriage on growth retardation in low-income countries.
Project description:BACKGROUND AND PURPOSE:As survival rates have increased for intracerebral hemorrhage (ICH) patients, there is limited information regarding recovery beyond 3-6 months. This study was conducted to examine recovery curves using the modified Rankin Scale (mRS) and Barthel Index (BI) up to 12 months post-injury. METHODS:We prospectively enrolled 173 patients admitted with ICH who were subsequently evaluated using the mRS and BI at discharge as well as 3, 6, and 12 months. Repeated measures nonparametric testing was conducted to assess functional trajectories across time. RESULTS:The mRS scores showed significant improvement between discharge (median 4) and 3 (median 4), 6 (median 4), and 12 months (median 3) (p values <0.001). However, the mRS scores did not differ between follow-up time-points (i.e., 3-6, 6-12 months). There was significant improvement in scores using the BI (p values <0.001), showing improvement between discharge (mean 43.0) and 3 (mean 73.0), 6 (mean 78.2), and 12 months (mean 83.4). Additionally, there were differences in the BI between 3 and 12 months (p = 0.013), as well as between 6 and 12 months (p = 0.025). CONCLUSIONS:The BI may be a more sensitive measure of long-term recovery post-injury than the mRS, which shows minimal improvement for some survivors after 3 months. BI scores indicate survivors continually improve till 12 months post-injury. These results may have implications for the prognostication of ICH and design of clinical trial outcome measures.
Project description:BackgroundPrevalence of antenatal depression in low and middle income countries is high. However studies examining the association between maternal antenatal depression and early childhood development from these countries are scarce. The objective of the study was to examine the association between antenatal depressive symptoms assessed serially during pregnancy and child neurodevelopment outcomes in mother-child dyads part of a randomized control trial of maternal B12 supplementation during pregnancy.MethodSubjects were 203 women who had participated in the placebo-controlled, randomized trial of vitamin B12 supplementation during pregnancy and 6 weeks post-partum on whom serial assessments of depressive symptoms in each of the trimesters were available. Cognitive, receptive language, expressive language, fine motor skills and gross motor skills were assessed at 30 months using the Bayley's Scale of Infant Development-3rd edition (BSID-III). Antenatal depressive symptoms were assessed at three trimesters using the Kessler's 10 Psychological Distress Scale (K10). Women were classified into three categories: not depressed (K10 <6 in all trimesters), with intermittent depressive symptoms (K10 ≥6 in at least one trimester) and with persistent depressive symptoms (K10 score ≥6 in at least 2 trimesters).Results112 (55.2%) of the women did not have depressive symptoms, 58 (28.6%) had intermittent depressive symptoms and 33 (16.2%) had persistent depressive symptoms. The children of women with intermittent antenatal depressive symptoms scored lower on the receptive language domain on BSID-III compared to children of women who were not depressed on univariate analysis, but not on bivariate regression analysis. Women with persistent depressive symptoms had lower educational attainment (p = 0.004), lower social support (p = 0.006) and used more emotional coping strategies (p = 0.005) compared to the not depressed group.ConclusionsA significant number of women in south India had antenatal depressive symptoms. Findings from this study suggest a possible association between antenatal depressive symptoms and receptive language in children. Larger studies including women with clinical depression are needed to confirm these findings.
Project description:BackgroundThere is much data available concerning the initiation of the immune response after SARS-CoV-2 infection, but long-term data are scarce.MethodsWe thus longitudinally evaluated and compared the total and neutralizing immune response of 61 patients to SARS-CoV-2 infection up to eight months after diagnosis by RT-PCR using several commercial assays.ResultsAmong the 208 samples tested, the percentage of seropositivity was comparable between assays up to four months after diagnosis and then tended to be more heterogeneous between assays (p < 0.05). The percentage of patients with a neutralizing titer decreased from 82% before two months postdiagnosis to 57% after six months. This decrease appeared to be more marked for patients under 65 years old and those not requiring hospitalization. The percentage of serology reversion at 6 months was from 11% with the WANTAI total assay to over 39% with the ABBOTT IgG assay. The neutralizing antibody titers decreased in parallel with the decrease of total antibody titers, with important heterogeneity between assays.ConclusionsIn conclusion, serological tests show equivalent sensitivity in the first months after the diagnosis of SARS-CoV-2 infection, but their performance later, postinfection, must be considered when interpreting the results.