Oxidative stress and viral Infections: rationale, experiences, and perspectives on N-acetylcysteine.

This article explores current evidence on the role of oxidative stress in viral infections, and on the use of antioxidant drugs as adjunctive treatment. MEDLINE/PubMed was searched for appropriate keywords, and preclinical and clinical studies with reviews were retrieved and examined by authors. Old and current evidence shows that GSH content reduction is the main mechanism of redox imbalance in viral-infected cells. Clinical studies found that GSH levels are depleted in patients with viral infections such as HIV and SARS-CoV. Viral infections activate inflammation through different pathways, and several of these mechanisms are related to oxidative stress. NAC is a precursor of GSH, and many of its intracellular effects are mediated by GSH replenishment, but it also activates some anti-inflammatory mechanisms. NAC has an excellent safety profile and better oral and topical bioavailability than GSH. These characteristics make NAC a suitable option as a repurposed drug. Adjunctive antioxidant treatment may improve the outcomes of antiviral therapies. Current evidence supports the rationale for this practice and some clinical experience showed encouraging results.

144 Probable Delirium is A Presenting Symptom of COVID-19 in Frail, Older Adults: A Study of Hospitalised and Community-Based Cohorts

Introduction COVID-19 exhibits a more severe disease course in older adults with frailty. Awareness of atypical presentations is critical to facilitate early disease identification. This study aimed to assess how frailty affects presenting symptoms of COVID-19 in older adults. Methods Observational study of two distinct cohorts: (i) Hospitalised patients aged 65 and over;unscheduled admission to a large London teaching hospital between March 1st, 2020-May 5th, 2020;COVID-19 confirmed by RT-PCR of nasopharyngeal swab (n = 322);(ii) Community-based adults aged 65 and over enrolled in the COVID Symptom Study mobile application between March 24th (application launch)-May 8th, 2020;self-report or report-by-proxy data;reported test-positive for COVID-19 (n = 535). Multivariable logistic regression analysis performed on age-matched samples of both cohorts to determine associations between frailty and symptoms of COVID-19 including delirium, fever and cough. Results Hospital cohort: there was a significantly higher prevalence of delirium amongst the frail sample, with no difference in fever or cough. Of those presenting with delirium, 10/53 (18.9%) presented with delirium as the only documented symptom. Community-based cohort: there was a significantly higher prevalence of probable delirium in the frail sample, and also of fatigue and shortness of breath. Of those reporting probable delirium, 28/84 (33%) did not report fever or cough. Conclusions This study demonstrates a higher prevalence of delirium as a presenting symptom of COVID-19 infection in older adults with frailty compared to their age-matched non-frail counterparts. Clinicians should suspect COVID-19 in frail older adults presenting with delirium. Early detection facilitates infection control measures to mitigate against catastrophic spread and preventable hospitalisations and deaths amongst this population. Our findings emphasise the need for systematic frailty assessment for all acutely ill older patients in both hospital and community settings, as well as systematic evaluation of any change in mental status.

Diagnostic value of cutaneous manifestation of SARS-CoV-2 infection.

BACKGROUND: One of the challenging aspects of SARS-CoV-2 infection is its diverse multisystemic disease presentation. OBJECTIVES: To evaluate the diagnostic value of cutaneous manifestations of SARS-CoV-2 infection and investigate their duration and timing in relation to other COVID-19 symptoms. METHODS: We used data from 336 847 UK users of the COVID Symptom Study app to assess the diagnostic value of body rash or an acral rash in SARS-CoV-2 infection, and data from an independent online survey of 11 544 respondents to investigate skin-specific symptoms and collect their photographs. RESULTS: Using data from the app, we show significant association between skin rashes and a positive swab test result (odds ratio 1·67, 95% confidence interval 1·42-1·97). Strikingly, among the respondents of the independent online survey, we found that 17% of SARS-CoV-2-positive cases reported skin rashes as the first presentation, and 21% as the only clinical sign of COVID-19. Together with the British Association of Dermatologists, we have compiled a catalogue of images of the most common skin manifestations of COVID-19 from 400 individuals (https://covidskinsigns.com), which we have made publicly available to assist clinicians in recognition of this early clinical feature of COVID-19. CONCLUSIONS: Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test, and occur in a significant number of cases, either alone or before other classical symptoms. Recognizing rashes is important in identifying new and earlier cases of COVID-19.