New data published today in Clinical Infectious Diseases indicates that early implementation of shorter treatment regimens for drug-resistant tuberculosis (TB) in the United States was successful.

The data come from a cohort of 70 US patients who were started on the 6-month, all-oral bedaquiline, pretomanid, and linezolid (BPaL) regimen for rifampin-resistant TB (RR-TB) in October 2019, shortly after the US Food and Drug Administration approved the regimen. The data on treatment outcomes were collected and analyzed by the BPaL Implementation Group (BIG). Because data from several trials indicated a high rate of adverse events with 1,200 milligrams (mg) of linezolid, most of the US patients treated with the BPaL regimen were started with a 600-mg linezolid dose based on the determination of their provider and had the dosage adjusted by therapeutic drug monitoring (TDM).

Of the 70 patients (65.7% male, 90% non–US-born, 77.9% non-White), 68 (97.1%) completed BPaL treatment. Fifty-five patients (80.9%) who completed BPaL had at least 6 months of follow-up without relapse, 36 (52.9%) had at least 12 months, and 19 (27.9%) had at least 24 months. Two patients (2.9%) were lost to follow-up after treatment completion, three (4.4%) after 6 months of treatment, and two (2.9%) experienced relapse.

Using an initial 600-mg linezolid dose daily adjusted by TDM and careful clinical and laboratory monitoring for side effects, supportive care, and expert consultation throughout BPaL treatment, three patients with hematologic toxicity (4.4%) and four with neurotoxicity (5.9%) required a change in linezolid dose or frequency. The median BPaL duration was 6 months.

Early implementation of new tuberculosis treatments is feasible, serving as a model for future innovations.

The study authors say the BPaL regimen has "transformed" treatment for drug-resistant TB in the United States. Previous RR-TB regimens were as long as 24 months, with poorer outcomes. From 2014 through 2018, only 62% of the 618 US patients with RR-TB completed the treatment, with 8% dying before treatment completion.

"The BIG cohort demonstrates that, with collaborative efforts among providers and public health programs, early implementation of new tuberculosis treatments is feasible, serving as a model for future innovations," they wrote.

Working the night shift or binge drinking may double the risk of COVID-19 infection, according to a study of nurses published this week in Alcohol: Clinical and Experimental Research. Poor sleep quality and binge drinking have been associated with COVID-19 infections, likely because both promote a pro-inflammatory state.

Because nurses were regularly exposed to COVID during the pandemic, had a high-stress job, and work during overnight shifts, the authors of the study hypothesized that shift work and alcohol misuse would be associated with COVID-19 infections.

Results were based on 750 responses from members of the American Nurses Association, who were asked to complete an online survey about alcohol use, sleep patterns, chronotype, and history of COVID-19 infections. A chronotype is someone's preferred sleep pattern, such as being an early bird or night owl. The online survey was available from May 2020 to April 2021.

The mean age of study participants was 39 years. Ninety percent of respondents were women.

Twenty-five percent of the respondents met the criteria for alcohol misuse, with 5% classified as binge drinkers, or drinking more than six drinks in one sitting. Alcohol misuse was more than one drink per day for women, two drinks per day for men, or drinking more than four and five drinks in one sitting for women and men, respectively.

Late chronotype [sleep patterns] and binge alcohol were associated with an increased risk of COVID-19 infection.

The authors found the night shift was associated with more than double the odds of COVID-19 infection compared with the standard shift (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.18 to 6.07). Binge drinkers had twice the odds of COVID-19 infection of those with low-risk features (OR, 2.08; 95% CI; 0.75 to 5.79).

"Late chronotype and binge alcohol were associated with an increased risk of COVID-19 infection, which strongly suggests alcohol and circadian misalignment are both cofactors in COVID-19 disease in exposed individuals," the authors concluded. "This study supports further examination of key mechanisms that relate to increased susceptibility of COVID-19 infection with alcohol and circadian misalignment to mitigate the impact of COVID-19 infection on frontline healthcare workers."

Australian First Nations (FN) people, who, like other indigenous populations, are at high risk for poor COVID-19 outcomes, have robust immune responses to the Pfizer/BioNTech vaccine,  finds a study published yesterday in Nature Immunology.

A University of Melbourne-led team evaluated immune responses in 97 COVID-naïve adults (58 FN people and 39 nonindigenous people from Darwin, Northern Territory) in 2021 or 2022. The researchers performed sampling before the first dose, 6 to 28 days after dose 1, before dose 2, 28 days after dose 2, 6 months after dose 2, and 28 days after dose 3.

Median participant age was 44 years, and 47% and 74% of participants in the Australian FN group and the nonindigenous people, respectively, were women.

Lower response in those with chronic conditions

Australian FN people elicited effective immune responses to vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike–specific B cells, and CD4⁺ and CD8⁺ T cells.

In FN participants, RBD immunoglobulin G (IgG) antibody levels were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells, and follicular helper T cells were observed in vaccinated participants with chronic conditions such as diabetes and kidney disease and were strongly tied to altered glycosylation of IgG and increased interleukin-18 plasma levels.

We saw high levels of antibodies binding to the virus following two vaccine doses.

These changed immune responses were also seen in nonindigenous people with chronic conditions, which the study authors said indicates the changes were related to the conditions rather than to ethnicity. Vaccine-induced antibody responses against the SARS-CoV-2 Delta and Omicron variants were lower but rose substantially after the third dose, similar to those in previous studies among nonindigenous people.

"We saw high levels of antibodies binding to the virus following two vaccine doses," said lead author Wuji Zhang, a PhD candidate, in a University of Melbourne's Peter Doherty Institute for Infection and Immunity news release. "T cells against the spike protein, which often recognise small sections of the virus and are similar across different variants, were also seen in higher numbers and showed 'memory signatures' following vaccination."