Persistence of clinically relevant levels of SARS-CoV2 envelope gene subgenomic RNAs in non-immunocompromised individuals.

OBJECTIVES: This study aimed to evaluate the associations between COVID-19 severity and active viral load, and to characterize the dynamics of active SARS-CoV-2 clearance in a series of archival samples taken from patients in the first wave of COVID-19 infection in the South West of the UK. METHODS: Subgenomic RNA (sgRNA) and E-gene genomic sequences were measured in a retrospective collection of PCR-confirmed SARS-CoV-2-positive samples from 176 individuals, and related to disease severity. Viral clearance dynamics were then assessed in relation to symptom onset and last positive test. RESULTS: Whilst E-gene sgRNAs declined before E-gene genomic sequences, some individuals retained sgRNA positivity for up to 68 days. 13% of sgRNA-positive cases still exhibited clinically relevant levels of virus after 10 days, with no clinical features previously associated with prolonged viral clearance times. CONCLUSIONS: Our results suggest that potentially active virus can sometimes persist beyond a 10-day period, and could pose a potential risk of onward transmission. Where this would pose a serious public health threat, additional mitigation strategies may be necessary to reduce the risk of secondary cases in vulnerable settings.

Systolic blood pressure and outcomes in frail older adults.

Hypertension is diagnosed in the majority of older people with frailty, in whom blood pressure prognosis is not well understood. This editorial describes recent evidence on blood pressure and outcomes in older people with frailty.

COVID-19 severity is predicted by earlier evidence of accelerated aging.

With no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes [1]. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) [2] composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020) [3]. Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2×10-6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.