Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review

INTRODUCTION@#We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity.@*METHODS@#We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded.@*RESULTS@#169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum.@*CONCLUSION@#Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

Identifying COVID-19 cases in primary care settings

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 SARS-CoV-2 positive cases and 564 controls, accounting for the time course of illness at point of assessment. Clinical differentiators of cases and controls were used to derive model-based risk scores. Significant symptoms included abdominal pain, cough, diarrhea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5{degrees}C and 37.9{degrees}C, and temperature above 38{degrees}C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, we firstly used leave-one-out cross-validation, which confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. Secondly, in a separate ongoing prospective study of 237 COVID-19 and 346 primary care patients presenting with symptoms of acute respiratory infection, the baseline model had a sensitivity of 0.57 and specificity of 0.89, and in retrospective notes review of 100 COVID-19 cases diagnosed in primary care, sensitivity was 0.56. A web-app based tool has been developed for easy implementation as an adjunct to laboratory testing to differentiate COVID-19 positive cases among patients presenting in outpatient settings.