Association of gut microbiota with COVID-19 susceptibility and severity: A two-sample Mendelian randomization study.

Evidence supports the observational associations of gut microbiota with the risk of COVID-19; however, it is unclear whether these associations reflect a causal relationship. This study investigated the association of gut microbiota with COVID-19 susceptibility and severity. Data were obtained from a large-scale gut microbiota data set (n = 18 340) and the COVID-19 Host Genetics Initiative (n = 2 942 817). Causal effects were estimated with inverse variance weighted (IVW), MR-Egger, and weighted median, and sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. For COVID-19 susceptibility, IVW estimates suggested that Gammaproteobacteria (odds ratio [OR] = 0.94, 95% confidence interval [CI], 0.89-0.99, p = 0.0295] and Streptococcaceae (OR = 0.95, 95% CI, 0.92-1.00, p = 0.0287) had a reduced risk, while Negativicutes (OR = 1.05, 95% CI, 1.01-1.10, p = 0.0302), Selenomonadales (OR = 1.05, 95% CI, 1.01-1.10, p = 0.0302), Bacteroides (OR = 1.06, 95% CI, 1.01-1.12, p = 0.0283), and Bacteroidaceae (OR = 1.06, 95% CI, 1.01-1.12, p = 0.0283) were associated with an increased risk (all p < 0.05, nominally significant). For COVID-19 severity, Subdoligranulum (OR = 0.80, 95% CI, 0.69-0.92, p = 0.0018), Cyanobacteria (OR = 0.85, 95% CI, 0.76-0.96, p = 0.0062), Lactobacillales (OR = 0.87, 95% CI, 0.76-0.98, p = 0.0260), Christensenellaceae (OR = 0.87, 95% CI, 0.77-0.99, p = 0.0384), Tyzzerella3 (OR = 0.89, 95% CI, 0.81-0.97, p = 0.0070), and RuminococcaceaeUCG011 (OR = 0.91, 95% CI, 0.83-0.99, p = 0.0247) exhibited negative correlations, while RikenellaceaeRC9 (OR = 1.09, 95% CI, 1.01-1.17, p = 0.0277), LachnospiraceaeUCG008 (OR = 1.12, 95% CI, 1.00-1.26, p = 0.0432), and MollicutesRF9 (OR = 1.14, 95% CI, 1.01-1.29, p = 0.0354) exhibited positive correlations (all p < 0.05, nominally significant). Sensitivity analyses validated the robustness of the above associations. These findings suggest that gut microbiota might influence the susceptibility and severity of COVID-19 in a causal way, thus providing novel insights into the gut microbiota-mediated development mechanism of COVID-19.

Sleep and day-to-day PTSD symptom variability: an ecological momentary assessment and actigraphy monitored study in trauma-exposed young adults.

BACKGROUND: Disrupted sleep and post-traumatic stress disorder (PTSD) are bi-directionally linked and have been found to mutually reinforce each other on a day-to-day basis. However, most of the previous research has focused on subjective measures of sleep only. OBJECTIVE: Here, we investigated the temporal relationship between sleep and PTSD symptoms using both subjective (sleep diary) and objective measures of sleep (actigraphy). METHODS: Forty-one non-treatment seeking, trauma exposed young adults (age M = 24.68, SD = 8.15) with a range of PTSD symptom severities (PTSS, 0-53 on PCL-5) were recruited. Participants completed two surveys per day over four weeks to measure day-time PTSD symptoms (i.e. PTSS and number of intrusions) and night-time sleep subjectively, while wearing an actigraphy watch to measure sleep objectively. RESULTS: Linear mixed models revealed that subjectively reported sleep disruptions were associated with elevated next-day PTSS and increasing number of intrusive memories both within and between participants. Similar results were found for daytime PTSD symptoms on night-time sleep. However, these associations were not found using objective sleep data. Exploratory moderator analyses including sex (male vs. female) found that these associations differed in strength between sexes but were generally in the same direction. DISCUSSION: These results were in line with our hypothesis with regards to the sleep diary (subjective sleep), but not actigraphy (objective sleep). Several factors which have implications on both PTSD and sleep, such as the COVID-19 pandemic and/ or sleep-state misperception, may be potential reasons behind those discrepancies. However, this study had limited power and needs to be replicated in larger samples. Nonetheless, these results add to the current literature about the bi-directional relationship between sleep and PTSD and have clinical implications for treatment strategies.

Elevated day-time PTSD symptom severity (PTSS) and more frequent intrusive memories were generally associated with subjectively reported disruptions in sleep and vice versa, but not with objective measures of sleep.While longer subjective sleep duration predicted reductions in PTSS and shorter sleep onset latency predicted reduced numbers of intrusions the next day, reduced daytime PTSS was only associated with reductions in distress associated with nightmares during the following night.Exploratory analyses showed that sex (men vs. women) moderated the bi-directional relationships between night-time sleep and day-time PTSD symptoms with longer sleep onset latency and lower sleep efficiency being related to worse PTSD symptoms the next day in women, but was not associated with men.