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BackgroundA multitude of diagnostic and predictive algorithms have been designed for COVID-19. However, currently no score can accurately quantify and track day-to-day disease severity in hospitalised patients with COVID-19. We aimed to design such a score to improve pathophysiological insight in COVID-19.MethodsDevelopment of the Severity of COronavirus Disease Assessment (SCODA) score was based on the 4C Mortality score but patient demographic variables that remain constant during admission were excluded. Instead, parameters associated with breathing and oxygenation were added to reflect the daily condition. The SCODA score was subsequently applied to the BEAT-COVID cohort to describe COVID-19 severity over time and to determine the timing of clinical recovery for each patient, an important marker in pathophysiological studies. The BEAT-COVID study included patients with PCR confirmed COVID-19 who were hospitalized between April 2020 and March 2021 in the Leiden University Medical Center, The Netherlands.ResultsThe SCODA score consists of 6 clinical and 2 routine lab parameters. 191 patients participated in the BEAT-COVID study. Median age was 66, and 74.4% was male. The modal timepoint at which recovery was clinically initiated occurred on days 8 and 24 since symptom onset for non-ICU and ICU-patients, respectively.ConclusionsWe developed a daily score which can be used to track disease severity of patients admitted due to COVID-19. This score is useful for improving insight in COVID-19 pathophysiology, its clinical course and to evaluate interventions. In a future stage this score can also be used in other (emerging) infectious respiratory diseases.

Background: A multitude of diagnostic and predictive algorithms have been designed for COVID-19. However, currently no score can accurately quantify and track day-to-day disease severity in hospitalised patients with COVID-19. We aimed to design such a score to improve pathophysiological insight in COVID-19. Methods: Development of the Severity of COronavirus Disease Assessment (SCODA) score was based on the 4C Mortality score but patient demographic variables that remain constant during admission were excluded. Instead, parameters associated with breathing and oxygenation were added to reflect the daily condition. The SCODA score was subsequently applied to the BEAT-COVID cohort to describe COVID-19 severity over time and to determine the timing of clinical recovery for each patient, an important marker in pathophysiological studies. The BEAT-COVID study included patients with PCR confirmed COVID-19 who were hospitalized between April 2020 and March 2021 in the Leiden University Medical Center, The Netherlands. Results: The SCODA score consists of 6 clinical and 2 routine lab parameters. 191 patients participated in the BEAT-COVID study. Median age was 66, and 74.4% was male. The modal timepoint at which recovery was clinically initiated occurred on days 8 and 24 since symptom onset for non-ICU and ICU-patients, respectively. Conclusions: We developed a daily score which can be used to track disease severity of patients admitted due to COVID-19. This score is useful for improving insight in COVID-19 pathophysiology, its clinical course and to evaluate interventions. In a future stage this score can also be used in other (emerging) infectious respiratory diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects. METHOD: We vaccinated young volunteers (18-28 yrs, N = 30) and elderly travelers (60-81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination. RESULTS: Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8-4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1-2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants. CONCLUSIONS: We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD. TRIAL REGISTRATION: Trialregitser.nl NTR1040.

Implementation of yellow fever vaccination is currently hampered by limited supply of vaccine. An alternative route of administration with reduced amounts of vaccine but without loss of vaccine efficacy would boost vaccination programmes.A randomized, controlled, non-inferiority trial was conducted in a Dutch university center between August 2005 and February 2007. A total of 155 primary vaccinated and 20 previously vaccinated volunteers participated. Participants were randomly assigned in a 1ratio1 ratio to receive intradermal (i.d.) vaccination with live attenuated yellow fever 17D vaccine at a reduced dose (1/5(th); 0.1 mL) or the conventional subcutaneous (s.c.) vaccination (0.5 mL). Antibody neutralization titers were determined at 2, 4 and 8 weeks and 1 year after vaccination by counting the reduction in virus-induced plaques in the presence of serial serum dilutions. Adverse events were documented in a 3-week dairy. Viraemia was measured 5 days after vaccination. From 2 weeks up to one year after vaccination, the maximum serum-dilution at which 80% of the virus plaques were neutralized, which indicates protection against yellow fever, did not differ between those given a reduced i.d. dose or standard s.c. dose of vaccine. In all cases the WHO standard of seroprotection (i.e. 80% virus neutralization) was reached (in 77/77 and 78/78, respectively). Similar results were found in the previously vaccinated individuals. Viraemia was detected in half of the primary vaccinated participants, which was not predictive of serological response. In revaccinees no viraemia was detected.Intradermal administration of one fifth of the amount of yellow fever vaccine administered subcutaneously results in protective seroimmunity in all volunteers. Albeit this vaccination route should enable vaccination of five-times as many individuals at risk for disease, these results should now be confirmed in field studies in areas with potential yellow fever virus transmission to change vaccination policy.Nederlands Trial Register ISRCTN46326316.