Predictors for development of critical illness amongst older adults with COVID-19: Beyond age to age-associated factors.

INTRODUCTION: Older adults with COVID-19 have disproportionately higher rates of severe disease and mortality. It is unclear whether this is attributable to age or attendant age-associated risk factors. This retrospective cohort study aims to characterize hospitalized older adults and examine if comorbidities, frailty and acuity of clinical presentation exert an age-independent effect on COVID-19 severity. METHODS: We studied 275 patients admitted to the National Centre of Infectious Disease, Singapore. We measured: 1)Charlson Comorbidity Index(CCI) as burden of comorbidities; 2)Clinical Frailty Scale(CFS) and Frailty Index(FI); and 3)initial acuity. We studied characteristics and outcomes of critical illness, stratified by age groups (50-59,60-69 and ≥70). We conducted hierarchical logistic regression in primary model(N = 262, excluding direct admissions to intensive care unit) and sensitivity analysis(N = 275): age and gender in base model, entering CCI, frailty (CFS or FI) and initial acuity sequentially. RESULTS: The ≥70 age group had highest CCI(p<.001), FI(p<.001) and CFS(p<.001), and prevalence of geriatric syndromes (polypharmacy,53.5%; urinary symptoms,37.5%; chronic pain,23.3% and malnutrition,23.3%). Thirty-two (11.6%) developed critical illness. In the primary regression model, age was not predictive for critical illness when a frailty predictor was added. Significant predictors in the final model (AUC 0.809) included male gender (p=.012), CFS (p=.038), and high initial acuity (p=.021) but not CCI or FI. In sensitivity analysis, FI (p=.028) but not CFS was significant. CONCLUSIONS: In hospitalized older adults with COVID-19, geriatric syndromes are not uncommon. Acuity of clinical presentation and frailty are important age-independent predictors of disease severity. CFS and FI provide complimentary information in predicting interval disease progression and rapid disease progression respectively.

Associations of viral ribonucleic acid (RNA) shedding patterns with clinical illness and immune responses in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

OBJECTIVES: A wide range of duration of viral RNA shedding in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been observed. We aimed to investigate factors associated with prolonged and intermittent viral RNA shedding in a retrospective cohort of symptomatic COVID-19 patients. METHODS: Demographic, clinical and laboratory data from hospitalised COVID-19 patients from a single centre with two consecutive negative respiratory reverse transcription-polymerase chain reaction (RT-PCR) results were extracted from electronic medical records. Kaplan-Meier survival curve analysis was used to assess the effect of clinical characteristics on the duration and pattern of shedding. Plasma levels of immune mediators were measured using Luminex multiplex microbead-based immunoassay. RESULTS: There were 201 symptomatic patients included. Median age was 49 years (interquartile range 16-61), and 52.2% were male. Median RNA shedding was 14 days (IQR 9-18). Intermittent shedding was observed in 77 (38.3%). We did not identify any factor associated with prolonged or intermittent viral RNA shedding. Duration of shedding was inversely correlated with plasma levels of T-cell cytokines IL-1ß and IL-17A at the initial phase of infection, and patients had lower levels of pro-inflammatory cytokines during intermittent shedding. CONCLUSIONS: Less active T-cell responses at the initial phase of infection were associated with prolonged viral RNA shedding, suggesting that early immune responses are beneficial to control viral load and prevent viral RNA shedding. Intermittent shedding is common and may explain re-detection of viral RNA in recovered patients.