Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

Infection with novel SARS-CoV-2 carries significant morbidity and mortality in patients with pulmonary compromise, such as lung cancer, autoimmune disease, and pneumonia. For early stages of mild to moderate disease, care is entirely supportive.Antiviral drugs such as remdesivir may be of some benefit but are reserved for severe cases given limited availability and potential toxicity. Repurposing of safer, established medications that may have antiviral activity is a possible approach for treatment of earlier-stage disease. Tetracycline and its derivatives (e.g. doxycycline and minocycline) are nontraditional antibiotics with a well-established safety profile, potential efficacy against viral pathogens such as dengue fever and chikungunya, and may regulate pathways important in initial infection, replication, and systemic response to SARS-CoV-2. We present a series of four high-risk, symptomatic, COVID-19+ patients, with known pulmonary disease, treated with doxycycline with subsequent rapid clinical improvement. No safety issues were noted with use of doxycycline.Doxycycline is an attractive candidate as a repurposed drug in the treatment of COVID-19 infection, with an established safety profile, strong preclinical rationale, and compelling initial clinical experience described here.The reviews of this paper are available via the supplemental material section.

Sexual Dimorphism of Resting-State Network Connectivity in Healthy Ageing.

OBJECTIVES: The onset of many illnesses is confounded with age and sex. Increasing age is a risk factor for the development of many illnesses, and sexual dimorphism influences brain anatomy, function, and cognition. Here, we examine frequency-specific connectivity in resting-state networks in a large sample (n = 406) of healthy aged adults. METHOD: We quantify frequency-specific connectivity in three resting-state networks known to be implicated in age-related decline: the default mode, dorsal attention, and salience networks, using multiband functional magnetic resonance imaging. Frequency-specific connectivity was quantified in four bands: low (0.015-0.027 Hz), moderately low (0.027-0.073 Hz), moderately high (0.073-0.198 Hz), and high (0.198-0.5 Hz) frequency bands, using mean intensity and spatial extent. Differences in connectivity between the sexes in each of the three networks were examined. RESULTS: Each network showed the largest intensity and spatial extent at low frequencies and smallest extent at high frequencies. Males showed greater connectivity than females in the salience network. Females showed greater connectivity than males in the default mode network. DISCUSSION: Results in this healthy aged cohort are compatible with those obtained in young samples, suggesting that frequency-specific connectivity, and differences between the sexes, are maintained into older age. Our results indicate that sex should be considered as an influencing factor in studies of resting-state connectivity.