Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2.

Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used 'omic" assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4+ T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8+ T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

Testing the test strips: laboratory performance of fentanyl test strips.

BACKGROUND: The overdose crisis driven by synthetic opioids continues to escalate in the USA. We evaluated the efficacy of multiple manufacturing lots of a fentanyl test strip (FTS) to detect fentanyl and fentanyl analogs and assessed cross-reactivity with possible interferences. METHODS: Drug standards were dissolved in water in a laboratory setting and serially diluted. Drug dilutions were tested using five different manufacturing lots of BTNX Rapid Response (20 ng/mL cutoff) lateral flow chromatographic immunoassay strips to assess lot-to-lot variability for FTS sensitivity and cross-reactivity for the analytes of interest. RESULTS: All five manufacturing lots cross-reacted with fentanyl and eleven fentanyl analogs. Diphenhydramine, lidocaine, MDMA, and methamphetamine were found to cause false positives with the strips. There was notable lot-to-lot variability in the sensitivity of the strips for fentanyl, fentanyl analogs, and known interferences. DISCUSSION: FTS remains an important overdose prevention tool, but lot-to-lot variability in performance complicates robust instructions that balance the prevention of false positives and false negatives. Continued lot-to-lot performance assessment is recommended to ensure health education for FTS remains accurate. More sophisticated drug checking technologies and services are needed in the community landscape to augment personal FTS use to facilitate informed consumption and overdose risk mitigation.

Brief Report: The Role of Substance Use in Structural Heart Disease Among Women Living With HIV.

BACKGROUND: People living with HIV have increased risk of cardiovascular disease, but few studies focus on women with HIV (WWH) and few account for the use of multiple substances. SETTING: We recruited WWH from San Francisco shelters, free meal programs, street encampments, and a safety net HIV clinic. METHODS: Between 2016 and 2019, participants completed 6 monthly interviews, specimen collection, and a transthoracic echocardiogram. We assessed associations between 3 echocardiographic indices of cardiac hypertrophy (concentric hypertrophy, concentric remodeling, and eccentric hypertrophy) and study factors, including cardiovascular risk factors, substance use, and HIV-specific factors (CD4 + count, viral load, HIV medication). RESULTS: Among 62 participants, the average age was 53 years and 70% were ethnic minority women. Just over 70% had elevated blood pressure. Toxicology-confirmed substance use included tobacco (63%), cannabis (52%), cocaine (51%), methamphetamine (29%), and alcohol (26%). Concentric hypertrophy was detected in 26% of participants. It was positively associated with cocaine use [adjusted relative risk (aRR) = 32.5, P < 0.01] and negatively associated with cannabis use (aRR = 0.07, P < 0.01). Concentric remodeling was detected in 40% of participants. It was positively associated with cocaine use (aRR = 11.2, P < 0.01) and negatively associated with cannabis use (aRR = 0.17, P = 0.02). Eccentric hypertrophy was not significantly associated with factors studied here. CONCLUSIONS: Routine evaluation of stimulant use as a contributing factor to cardiovascular risk may improve risk assessment in WWH. Whether cannabis use mitigates the impact of cocaine use on structural heart disease among WWH merits further investigation.