Factors influencing the immune response over 15 months after SARS-CoV-2 infection: A longitudinal population-wide study in the Faroe Islands.

BACKGROUND: The durability of SARS-CoV-2 antibody response and the resulting immunity to COVID-19 is unclear. OBJECTIVES: To investigate long-term humoral immunity to SARS-CoV-2. METHODS: In this nationwide, longitudinal study, we determined antibody response in 411 patients aged 0-93 years from two waves of infections (March to December 2020) contributing 1063 blood samples. Each individual had blood drawn on 4-5 occasions 1-15 months after disease onset. We measured total anti-SARS-CoV-2 receptor-binding domain (RBD) antibody using a qualitative RBD sandwich ELISA, IgM, IgG and IgA levels using an quantitative in-house ELISA-based assay  and neutralizing antibodies (NAbs) using an in-house ELISA-based pseudoneutralizing assay. IgG subclasses were analyzed in a subset of samples by ELISA-based assay. We used nonlinear models to study the durability of SARS-CoV-2 antibody responses and its influence over time. RESULTS: After 15 months, 94% still had detectable circulating antibodies, mainly the IgG isotype, and 92% had detectable NAbs. The distribution of IgG antibodies varied significantly over time, characterized by a biphasic pattern with an initial decline followed by a plateau after approximately 7 months. However, the NAbs remained relatively stable throughout the period. The strength of the antibody response was influenced by smoking and hospitalization, with lower IgG levels in smokers and higher levels in hospitalized individuals. Antibody stability over time was mainly associated with male sex and older age with higher initial levels but more marked decrease. CONCLUSIONS: The humoral immune response to SARS-CoV-2 infection varies depending on behavioral factors and disease severity, and antibody stability over 15 months was associated with sex and age.

Association between maternal weight gain and birth weight.

OBJECTIVE: To investigate the association between maternal weight gain and birth weight less than 3,000 g and greater than or equal to 4,000 g in underweight (body mass index [BMI] less than 19.8 kg/m(2)), normal weight (BMI 19.8-26.0 kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI greater than 29.0 kg/m(2)) women, with emphasis on the use of the American Institute of Medicine (IOM) recommendations in Denmark. METHODS: We analyzed data from 2,248 women with singleton, term pregnancies. The relationship between weight gain and risk of birth weight less than 3,000 g and greater than or equal to 4,000 g was examined in the four BMI groups, and use of IOM recommendations was tested by logistic regression analyses. RESULTS: We found an inverse relationship between maternal weight gain and the proportion of infants with a birth weight less than 3,000 g. Birth weight greater than or equal to 4,000 g increased with an increasing weight gain in underweight and normal-weight women, but the association was less apparent in overweight and obese women. Underweight women seemed to benefit from gaining more weight than recommended by the IOM, because the odds ratio (OR) of birth weight less than 3,000 g was 0.3 (95% confidence interval [CI] 0.1-0.9) and the OR was 1.7 for birthweight greater than or equal to 4,000 g (95% CI 0.8-3.6). The normal-weight women had an increased risk of birth weight less than 3,000 g (OR 2.4, 95% CI 1.5-3.7) if weight gain was below the recommended range, and the OR of birth weight greater than or equal to 4,000 g was 1.9 (95% CI 1.5-2.5) when the women gained more than recommended. CONCLUSION: The IOM recommendations may provide a basis for Danish recommendations to pregnant women, although the upper recommended limit for underweight women may have to be increased.

Determination of a saliva cotinine cut-off to distinguish pregnant smokers from pregnant non-smokers.

BACKGROUND: Objective validation of smoking status is necessary. Earlier studies have used saliva cotinine concentrations between 14.2 and 30 ng/ml as cut-off values to distinguish pregnant smokers from non-smokers. However, these cut-offs derive from studies including men and non-pregnant women. This constitutes a problem, as recent studies have reported an accelerated metabolism in pregnant smokers. The aim of this study was to determine the optimum cut-off cotinine level distinguishing pregnant smokers from pregnant non-smokers. METHODS: An observational study of 620 pregnant women, 359 self-reported smokers and 261 self-reported non-smokers, with complete data on smoking status and saliva cotinine. The study was conducted at a large university hospital in Copenhagen, Denmark. Saliva was sampled at the first antenatal visit to the midwife and analyzed for cotinine level by gas chromatography. Participants completed a questionnaire immediately after the first visit. RESULTS: A saliva cotinine cut-off level of 13 ng/ml, corresponding to a sensitivity of 0.99 and specificity 0.98, was found to be the optimum cut-off value separating pregnant smokers from non-smokers. The sum of the sensitivity and specificity was at its maximum, 1.981. A 95% bootstrap confidence interval for the optimum cut-off was (8-14 ng/ml). CONCLUSION: From the present data we recommend that in future studies on smoking cessation and pregnancy a cut-off level of 13 ng/ml should be applied to distinguish between pregnant smokers and non-smokers.

The effect of environmental tobacco smoke during pregnancy on birth weight.

BACKGROUND: This study explores whether pregnant nonsmokers' exposure to environmental tobacco smoke (ETS) affects the average birth weight at term. METHODS: The population studied consists of pregnant nonsmokers participating in a study called Smoke-free Newborn Study. The participants (n = 1612) answered a questionnaire during 12th to 16th gestational week about their exposure to ETS at home and outside the home. RESULTS: Pregnant nonsmokers exposed to ETS both at home and outside the home gave birth to children with a birth weight of 78.9 g (95% CI -143.7 to -14.1) (P=0.02) lower than the weight of children born to women unexposed to ETS. There was no significant reduction in birth weight among women exposed to ETS at home only or outside the home only. A nonsignificant dose-response association was seen between increasing daily exposure to ETS and reduction in birth weight. CONCLUSION: Nonsmoking pregnant women who were exposed to ETS at home as well as outside the home gave birth to children with a 79 g reduction in birth weight compared to children of unexposed women. The fact that exposure to ETS has an effect on the birth weight is regarded as essential. The authors recommend that pregnant women should not be exposed to passive smoking, and that it should be considered whether workplace legislation should be instituted in order to protect pregnant women against the adverse effects of passive smoking.

Multimodal intervention raises smoking cessation rate during pregnancy.

BACKGROUND: The aim was to study the effect of a multimodal smoking cessation intervention regimen on a number of pregnant smokers. METHODS: A prospective intervention study was designed where participants were allocated to intervention or control based on their birth date. The study included 647 pregnant smokers. The intervention group (n = 327) received initial individual smoking cessation counseling supplemented by an invitation to join, individually or in a group, a smoking cessation program with nicotine replacement therapy as a voluntary option. Intervention was designed as an integral part of the midwives' prenatal care. All pregnant smokers in the usual care group (n = 320) received standard counseling from a midwife. Outcome was self-reported smoking cessation in the 37th week of pregnancy and the reported cessation was validated by cotinine saliva concentration. RESULTS: Self-reported cessation rates during pregnancy were significantly higher in the intervention group (14%) than in the group receiving usual care (5.0%) (p < 0.0001) (Fisher's exact test). Cotinine-validated cessation rates during pregnancy were significantly higher among the former (7%) than the latter (2%) (p = 0.003). The adjusted odds ratio (OR) for smoking cessation was 4.20 (95% CI 2.13-8.03). Logistic regression analysis showed a significant positive association of smoking cessation with low caffeine consumption in pregnancy, many years in school, no exposure to passive smoking outside the home, and previous attempts to stop smoking. CONCLUSIONS: A multimodal intervention regimen with initial individual counseling supplemented by an invitation to join a smoking cessation program with nicotine replacement therapy as a voluntary option markedly increased cessation rates during pregnancy.