COVID-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial

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. Log 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

A radiologic syndrome after high dose chemotherapy and autologous bone marrow transplantation, with clinical and pathologic features of systemic candidiasis

Background. The use of high dose chemotherapy in the treatment of solid tumors is associated with prolonged neutropenia and, consequently, in some patients, systemic candidiasis. The authors describe their experience with a clinicoradiologic syndrome developing after high dose chemotherapy was administered to patients with breast cancer. Methods. The authors evaluated the clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal candidiasis developed. Results. Three patients had positive blood cultures for candida tropicalis. One of these patients and two others had fungal organisms identified with special stains of an organ aspirate. Most patients were asymptomatic, and most of them were treated successfully with antifungal agents, although untreated patients also recovered. There were no fatalities due to the candidiasis. Conclusions. A radiographic syndrome resembling hepatic, splenic, or renal candidiasisis is described, which occurred after high dose chemotherapy was administered and autologous bone marrow transplantation was performed on patients with breast cancer. This syndrome has a favorable prognosis. Conclusions as to the more indolent nature of this syndrome cannot be made; however, this topic warrants further investigation

Risk factors for severe illness in hospitalized Covid-19 patients at a regional hospital

BACKGROUND: The Covid-19 pandemic threatens to overwhelm scarce clinical resources. Risk factors for severe illness must be identified to make efficient resource allocations. OBJECTIVE: To evaluate risk factors for severe illness. DESIGN: Retrospective, observational case series. SETTING: Single-institution. PARTICIPANTS: First 117 consecutive patients hospitalized for Covid-19 from March 1 to April 12, 2020. EXPOSURE: None. MAIN OUTCOMES AND MEASURES: Intensive care unit admission or death. RESULTS: In-hospital mortality was 24.8% and average total length of stay was 11.82 days (95% CI: 10.01 to 13.63 days). 30.8% of patients required intensive care unit admission and 29.1% required mechanical ventilation. Multivariate regression identified the amount of supplemental oxygen required at admission (OR: 1.208, 95% CI: 1.011–1.443, p = .037), sputum production (OR: 6.734, 95% CI: 1.630–27.812, p = .008), insulin dependent diabetes mellitus (OR: 11.873, 95% CI: 2.218–63.555, p = .004) and chronic kidney disease (OR: 4.793, 95% CI: 1.528–15.037, p = .007) as significant risk factors for intensive care unit admission or death. Of the 48 patients who were admitted to the intensive care unit or died, this occurred within 3 days of arrival in 42%, within 6 days in 71%, and within 9 days in 88% of patients. CONCLUSIONS: At our regional medical center, patients with Covid-19 had an average length of stay just under 12 days, required ICU care in 31% of cases, and had a 25% mortality rate. Patients with increased sputum production and higher supplemental oxygen requirements at admission, and insulin dependent diabetes or chronic kidney disease may be at increased risk for severe illness. A model for predicting intensive care unit admission or death with excellent discrimination was created that may aid in treatment decisions and resource allocation. Early identification of patients at increased risk for severe illness may lead to improved outcomes in patients hospitalized with Covid-19