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-Barre 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.

Automated summary

This study aimed to describe the extrapulmonary manifestations of SARS-CoV-2 infection, including their frequency, onset, pathogenesis, and association with disease severity. The study found that early manifestations included olfactory and gustatory disturbance, gastrointestinal symptoms, and rash, while later manifestations included multiorgan complications and thromboembolic events. Uncommon complications such as Guillain-Barre syndrome, rhabdomyolysis, otitis media, meningoencephalitis, and spontaneous pneumomediastinum were also identified. In conclusion, there are two phases of extrapulmonary disease in SARS-CoV-2 infection, with the need for a multidisciplinary consensus to approach and define thromboinflammation and cytokine release syndrome.