This study demonstrated significant associations between low vitamin D status and markers of inflammation (including the ratio of IL-6 to IL-10) within elderly adults. These findings suggest that an adequate vitamin D status may be required for optimal immune function, particularly within the older adult population.

BACKGROUND Vitamin B12 deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method. METHODS In elderly subjects (n = 700; age range 63–97 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L. RESULTS Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86–0.93), and this was significantly better (P ≤ 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75–0.85), and MMA, 0.78 (0.72–0.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20–30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin. CONCLUSIONS This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B12 status.

doi: medRxiv preprint Word Count: 3156 2 2 ABSTRACT 2 7Background: Reliable estimates of the incubation period are important for decision making around the 2 8 control of infectious diseases. Knowledge of the incubation period distribution can be used directly to 2 9 inform decision-making or as inputs into mathematical models. 3 0Objectives: The aim of this study was to conduct a rapid systematic review and meta-analysis of 3 1 estimates of the incubation periods of COVID-19. 3 2 Design: Rapid systematic review and meta-analysis of observational research 3 3 Data sources: Publications on the electronic databases PubMed, Google Scholar, MedRxiv and BioRxiv 3 4were searched. The search was not limited to peer-reviewed published data, but also included pre-print 3 5 articles. 6Study appraisal and synthesis methods: Studies were selected for meta-analysis if they reported either 3 7 the parameters and confidence intervals of the distributions fit to the data, or sufficient information to 3 8 facilitate calculation of those values. The majority of studies suitable for inclusion in the final analysis 3 9 modelled incubation period as a lognormal distribution. We conducted a random effects meta-analysis of 4 0 the parameters of this distribution. 4 1 Results: The incubation period distribution may be modelled with a lognormal distribution with pooled 4 2 mu and sigma parameters of 1.63 (1.51, 1.75) and 0.50 (0.45, 0.55) respectively. The corresponding mean 4 3

Background: Understanding the extent of virus transmission that can occur before symptom onset is vital for targeting control measures against the global pandemic of COVID-19.Objective: Estimation of (1) the proportion of pre-symptomatic transmission of COVID-19 that can occur and (2) timing of transmission relative to symptom onset. Design: Secondary analysis of published dataData sources: Meta-analysis of COVID-19 incubation period and a rapid systematic review of serial interval and generation time, which are published separately.Methods: Simulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset were calculated and the proportion of pre-symptomatic transmission was estimated. Results:A total of 23 estimates of serial interval and five estimates of generation time from 17 publications were included. These came from nine different data source categories (presented here in descending order of the proportion of pre-symptomatic transmission):Hong Kong, Tianjin, pooled data from Hong Kong and Shenzhen, Singapore, Mainland China excluding Hubei, mixed sources, Shenzhen, northern Italy and Wuhan. Transmission time relative to symptom onset ranged from a mean of 2.05 days before symptom onset for Hong Kong to 1.72 days after symptom onset for Wuhan. Proportion of pre-symptomatic transmission ranged from 33.7% in Wuhan to 72.7% in Hong Kong. Based on individual estimates, transmission time relative to symptom onset ranged from mean of 2.95 days before symptom onset to 1.72 days after symptom onset and proportion of pre-symptomatic transmission ranged from 33.7% to 79.9%. Simple unweighted pooling of estimates based on serial intervals resulted in a mean time of transmission of 0.67 days before symptoms, and an estimated 56.1% of transmission occurring in the pre-symptomatic period. Conclusions:Contact rates between symptomatic infectious and susceptible people are likely to influence the proportion of pre-symptomatic transmission. There is substantial potential for pre-symptomatic transmission of COVID-19 in a range of different contexts. Our work suggests that transmission of SARS-CoV-2 is most likely in the day before symptom onset whereas estimates suggesting most pre-symptomatic transmission highlighted a mean transmission times almost 3 days before symptom onset. These findings highlight the urgent need for extremely rapid and effective case detection, contact tracing and quarantine measures if strict social distancing measures are to be eased.

UVB-induced skin synthesis is considered the key source of vitamin D, yet exposure to UVB is poorly accounted for in epidemiological studies. The aim of this study was to examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with accurately measured ambient UVB dose, sun enjoyment, supplements, and other factors. An all-Irish cohort of community-dwelling participants aged >60 y [median age: 73; 67% female; median 25(OH)D: 54.5 nmol/L] was used. Participants from this large, cross-sectional study completed a questionnaire to provide information on demographic factors and lifestyle (including supplement use and sun enjoyment). The Tropospheric Emission Monitoring Internet Service database was used to extract the daily ambient UVB dose at wavelengths that could induce vitamin D synthesis (D-UVB) over Ireland (latitude: 51°N-55°N). Blood sampling occurred throughout the year. Ambient exposure at the place of residence was calculated for each participant individually. Associations between determinants and serum 25(OH)D concentration were examined in a multivariate model. Random forest analysis was used to establish prediction models of vitamin D deficiency, and area under the curve (AUC) is shown. In total, 5138 individuals were included. Median D-UVB was 63 mJ/cm, which varied between seasons and latitudes, despite the small latitude differential. Vitamin D supplementation (β = 27.7; < 10 × 10), D-UVB (β = 1.58 per 1000 mJ/cm; < 10 × 10), and sun enjoyment (β = 6.6; < 0.001) were strongly positively associated with serum 25(OH)D. Those who avoided sunshine were largely at risk of deficiency (<40 nmol/L), whereas those who enjoyed sunshine tended to be vitamin D sufficient (≥50 nmol/L). D-UVB and sun enjoyment improved prediction of deficiency in non-supplement-taking individuals; the overall AUC improved by 3.5%. D-UVB and sun enjoyment are important predictors of vitamin D status, even in this elderly population at northern latitudes. Accurate estimation of ambient UVB can help to further clarify the role of other determinants of vitamin D status and inform sunshine recommendation guidelines.