Clinical manifestations and health outcomes associated with Zika virus infections in adults: A systematic review

Background Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. Methods This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Findings We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. Conclusions The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.
Author summary Interest in Zika virus (ZIKV) has increased in the last decade due to its emergence and rapid spread in the Americas. In this review, we examine ZIKV clinical manifestations and sequelae in adults. Among studies reporting subjects with confirmed ZIKV and critical appraisal scores of at least 70%, symptoms reported include exanthema, fever, arthralgia, conjunctivitis, myalgia, headache, and diarrhea. Neurological sequelae in this group occurred in 0.3% of subjects, of which 75% were Guillain-Barré Syndrome (GBS). Recovery from GBS was variable: some patients returned to health and others endured chronic disability. Mortality was rare (0.1%). Hospitalization (11%) was often associated co-morbidities or GBS; this percentage perhaps reflects studies in which all reported subjects were hospitalized. Synthesizing reported data is challenging given the wide range of case definitions and ZIKV testing practices.