Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals. METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset. RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7). CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

Household Transmission of Influenza A Viruses in 2021-2022.

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. Exposures: Household contacts living with a primary case. Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder.

Disrupted sleep is a major feature in numerous clinical disorders and is related to decrements in affective memory processing. The prevalence of sleep disruption in post-traumatic stress disorder (PTSD) is suggested to be a key feature that exacerbates the impaired ability to recall extinction memories during experimental fear conditioning. We hypothesized that an intervention employing blue-wavelength light therapy (BLT) to regulate sleep and stabilize circadian rhythms in patients with PTSD (i.e., via regulated morning exposure) would be associated with PTSD symptom improvement, decreased sleep-related complaints, as well as improved consolidation and retention of extinction memories relative to a fear conditioning/extinction paradigm. Eighty-two individuals with PTSD underwent a well-validated fear conditioning/extinction protocol with subsequent assignment to receive morning BLUE (BLT) or placebo AMBER (ALT) light therapy daily for 30-min over 6-weeks. Participants returned after the intervention for post-treatment extinction recall, comprised of exposure to the previously conditioned stimuli, with the difference in skin conductance response between the "extinguished" and the "never-extinguished" stimuli at follow-up. Participants also viewed previously conditioned stimuli in a novel context during a functional magnetic resonance imaging (fMRI) scan. BLUE light therapy was associated with improvements relative to correlated decreases between PTSD symptoms and sleep-related complaints. Participants receiving BLT also sustained retention of the extinction memory, while those in the placebo amber light treatment group showed impairment, characterized by the restoration of the extinguished fear response after 6-weeks. Participants in the ALT also demonstrated greater reactivity in the left insula when viewing the previously extinguished fear-conditioned stimuli in a novel context. Daily BLUE-wavelength morning light exposure was associated with greater retention of extinction learning in patients with PTSD when compared to ALT, as supported by both autonomic and neurobiological reactivity. We speculate that improved sleep facilitated by a stabilized circadian rhythm, after fear-learning, led to greater consolidation of the fear extinction memory, decreased PTSD symptom presentation, and associated decreases in sleep-related complaints. Prominent exposure treatments for PTSD incorporate principles of fear extinction, and our findings suggest that blue light treatment may facilitate treatment gains by promoting the consolidation of extinction memories via improved sleep.