High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort.

End-stage renal disease (ESRD) patients are a population with high rates of COVID-19 and mortality. These patients present a low response to anti-SARS-CoV-2 immunization, which is associated with immune dysfunction. ESRD patients also present high plasma titers of Fibroblast Growth Factor 23 (FGF23), a protein hormone that reduces immune response in vivo and in vitro. Increased FGF23 levels associate with higher infection-related hospitalizations and adverse infectious outcomes. Thus, we evaluated whether ESRD patients with high FGF23 titers have an increased rate of SARS-CoV-2 infection. METHODS: We performed a prospective cohort of ESRD patients in hemodialysis who had measurements of plasma intact FGF23 in 2019. We determined COVID-19 infections, hospitalizations, and mortality between January 2020 and December 2021. RESULTS: We evaluated 243 patients. Age: 60.4 ± 10.8 years. Female: 120 (49.3%), diabetes: 110 (45.2%). During follow-up, 45 patients developed COVID-19 (18.5%), 35 patients were hospitalized, and 12 patients died (mortality rate: 26.6%). We found that patients with higher FGF23 levels (defined as equal or above median) had a higher rate of SARS-CoV-2 infection versus those with lower levels (18.8% versus 9.9%; Hazard ratio: 1.92 [1.03-3.56], p = 0.039). Multivariate analysis showed that increased plasma FGF23 was independently associated with SARS-CoV-2 infection and severe COVID-19. DISCUSSION: Our results suggest that high plasma FGF23 levels are a risk factor for developing COVID-19 in ESRD patients. These data support the potential immunosuppressive effects of high circulating FGF23 as a factor implicated in the association with worse clinical outcomes. Further data are needed to confirm this hypothesis.

Electroencephalography spectral edge frequency and suppression rate-guided sedation in patients with COVID-19: A randomized controlled trial.

Background: Sedation in coronavirus disease 2019 (COVID-19) patients has been identified as a major challenge. We aimed to investigate whether the use of a multiparameter electroencephalogram (EEG) protocol to guide sedation in COVID-19 patients would increase the 30-day mechanical ventilation-free days (VFD). Methods: We conducted a double-blind randomized clinical trial. We included patients with severe pneumonia due to COVID-19 who required mechanical ventilation (MV) and deep sedation. We randomized to the control (n = 25) or multiparameter group (n = 25). Sedation in the intervention group was administered following the standard institutional protocols together with a flow chart designed to reduce the propofol administration dose if the EEG suppression rate was over 2% or the spectral edge frequency 95 (SEF95) was below 10 Hz. We performed an intention-to-treat analysis to evaluate our primary outcome (30-day VFD). Results: There was no difference in VFD at day 30 (median: 11 [IQR 0-20] days in the control group vs. 0 [IQR 0-21] days in the BIS multiparameter group, p = 0.87). Among secondary outcomes, we documented a 17% reduction in the total adjusted propofol administered during the first 5 days of the protocol [median: 2.3 (IQR 1.9-2.8) mg/k/h in the control group vs. 1.9(IQR 1.5-2.2) mg/k/h in the MP group, p = 0.005]. This was accompanied by a higher average BIS value in the intervention group throughout the treatment period. Conclusion: A sedation protocol guided by multivariate EEG-derived parameters did not increase the 30-day VFD. However, the intervention led to a reduction in total propofol administration.

Emergence of SARS-CoV-2 Variants in the World: How Could This Happen?

The COVID-19 pandemic has had a significant global impact, with more than 280,000,000 people infected and 5,400,000 deaths. The use of personal protective equipment and the anti-SARS-CoV-2 vaccination campaigns have reduced infection and death rates worldwide. However, a recent increase in infection rates has been observed associated with the appearance of SARS-CoV-2 variants, including the more recently described lineage B.1.617.2 (Delta variant) and lineage B.1.1.529/BA.1 (Omicron variant). These new variants put the effectiveness of international vaccination at risk, with the appearance of new outbreaks of COVID-19 throughout the world. This emergence of new variants has been due to multiple predisposing factors, including molecular characteristics of the virus, geographic and environmental conditions, and the impact of social determinants of health that favor the genetic diversification of SARS-CoV-2. We present a literature review on the most recent information available on the emergence of new variants of SARS-CoV-2 in the world. We analyzed the biological, geographical, and sociocultural factors that favor the development of these variants. Finally, we evaluate the surveillance strategies for the early detection of new variants and prevent their distribution outside these regions.

Dysregulated Immune Responses in COVID-19 Patients Correlating With Disease Severity and Invasive Oxygen Requirements.

The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.

Implementation of a Palliative Hospital-Centered Spiritual and Psychological Telehealth System During COVID-19 Pandemic.

BACKGROUND: The severity of the COVID-19 pandemic has resulted in limited provision of palliative care and hospital teams have had to rise to the challenge of how to deliver care safely to people with palliative needs. Telehealth interventions have been seen as a useful resource with potential to improve clinical effectiveness. OBJECTIVE: To describe the implementation of a spiritual and psychological palliative telehealth system during the pandemic. METHODS: Pilot study based on the implementation of a telehealth system designed to support hospitalized patients referred to a mobile palliative care team, through synchronic videoconferences, and including patients' relatives. The implementation included protocol development, physical infrastructure, and training. The intervention consisted of spiritual and psychological telehealth sessions performed remotely by the chaplain and psychologist of a palliative care team. RESULTS: During the study period 59 patients were recruited, median age of 70 years, 57.6% females. The primary diagnosis was severe COVID-19 (50.8%), advanced cancer (32.2%) and advanced chronic illness (16.9%). A total of 211 telehealth sessions were carried out, 82% psychological and 18% spiritual. The main criteria for psychological sessions were being related to seriously ill patients with withdrawal or withholding of life-support treatment (60.1%). The main criteria for spiritual sessions were being a patient with spiritual suffering or requesting spiritual assistance (73.6%). An electronic user satisfaction survey indicated high satisfaction rates. CONCLUSION: This report demonstrates that it is possible to provide spiritual and psychological palliative care to hospitalized patients and families during pandemic restrictions through interdisciplinary telehealth delivery.