COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial.

IMPORTANCE: This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

Undetectable JC virus CSF PCR in patients with JC virus-induced progressive multifocal leukoencephalopathy.

The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC polyomavirus (JCPyV) PCR in CSF does not always rule out JCPyV-related PML. In this narrative review, we sought to examine the characteristic of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and provide alternative approaches in this scenario.

Joint Initiative Between Infectious Diseases and Podiatry in Outpatient Settings Improves Outcomes and Adherence to Treatment.

BACKGROUND: A joint infectious disease-podiatry clinic (JIDPC) in which an infectious diseases physician and a podiatrist see patients with diabetic foot infections together once a week was initiated in January 2017. This study was designed to investigate if the JIDPC can improve patient adherence and reduce recurrent infections. METHODS: A retrospective analysis of patients with diabetic foot infection admitted to Wheeling Hospital from March 2013 to December 2018 was performed. Initially, the patients were followed by infectious diseases and podiatry in their clinics separately (preintervention group). Beginning January 2017, they were followed together at the JIDPC (postintervention group). Recurrent infection, mortality, and loss to follow-up were compared using logistic regression models. RESULTS: Surgeries were performed in 52.5% of preintervention group participants (n = 99) and 81.9% of postintervention group participants (n = 55; P < .001). The preintervention group was more likely to be lost to follow-up (30.3% vs 9.1%; odds ratio [OR], 4.35 [confidence interval (CI), 1.58-11.99]), but the association was attenuated with further adjustment for surgery (OR 3.35 [CI, 1.17-9.62]). The risk of infection recurrence in 6 months was significantly higher in the preintervention group (36.1% vs 20.8%; OR, 2.16 [CI, 0.99-4.71]), but with further adjustment for surgery, this was not significant (P = .067; OR, 2.17 [CI, 0.95-4.94]). Mortality and 90-day readmission were not significantly different. CONCLUSIONS: Implementation of JIDPCs may decrease the incidence of recurrent infections among patients with diabetic foot infections.

Risk factors for acquisition of multidrug-resistant Acinetobacter baumannii among cancer patients.

BACKGROUND: Data regarding multidrug-resistant (MDR) Acinetobacter baumannii infections among cancer patients are limited. METHODS: We conducted a case-control study to investigate the risk factors for acquisition of MDR A baumannii and the outcomes among cancer patients. Cases were inpatients with malignancy who had MDR A baumannii from any cultures between 2008 and 2011. Controls were inpatients with malignancy but no MDR A baumannii. RESULTS: A total of 31 case patients were matched with 62 control patients. Hematologic malignancy (P = .036), need for dialysis (P = .01), admission for other reasons except elective surgery (P = .03), transfer from other health care facilities (P = .02), prolonged intensive care unit stay (P = .004), mechanical ventilation (P < .001), pressor use (P = .001), tube feeding (P < .001), transfusion (P = .009), and prior antimicrobial use (P < .001) were identified as significant risk factors in univariate analysis. Need for dialysis (odds ratio [OR], 18.23; P = .04) and prolonged intensive care unit stay (OR, 19.28; P = .01) remained significant in multivariate analysis. Lengths of stay were 28 days for the case patients and 10 days for the control patients (P = .001). The 90-day mortality rates were 41.9% and 29.0%, respectively (P = .20). CONCLUSIONS: Acquisition of MDR A baumannii among cancer patients appears to be associated with general nosocomial infection risk factors rather than underlying malignancies.