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OROV symptoms overlap with locally endemic arbovirus diseases, like dengue virus (DENV), complicating diagnosis. The study aimed to compare clinical, laboratory, and immunological profiles in OROV and DENV cases, crucial for improving diagnosis and management.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This study analyzed 51 OROV and 78 of DENV cases consecutively enrolled in Manaus, Amazonas, Brazil, and monitored for 28 days. OROV diagnosis was performed by real-time PCR (RT-PCR) using serum and urine samples. OROV RT-PCR positive samples were genotyped. A paired Plaque Reduction Neutralization Test (PRNT) was conducted on samples collected at D1 and D28. Patients with a\u2009\u2265\u20094-fold increase in neutralizing antibody titer between D1 and D28 were considered OROV-positive. Clinical manifestations, hematology, biochemistry, and cytokine profiles were analyzed. Statistical analysis included comparison between OROV and DENV patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Genome sequencing of OROV isolates confirmed presence of a previously reported novel reassortment event, consistent with ongoing localized transmission. Urine RT-PCR demonstrated low positivity compared to serum samples. The paired PRNT increased sensitivity in 45%. Clinically, OROV infection was associated with significantly higher frequencies of severe headache, myalgia, arthralgia, and rash compared to DENV infection (p\u2009&lt;\u20090.001). Elevated alanine aminotransferase (ALT) levels were also observed in OROV patients (p\u2009&lt;\u20090.001). Immunologically, OROV infection induced significantly increased levels of acute-phase CCL11 (eotaxin), CXCL10, IFN-\u03b3, IL-1RA, and IL-10, which declined by day 28, while IL-5 increased during recovery. In contrast, DENV patients exhibited elevated levels of CCL2, G-CSF, and CCL3 in recovery phase.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>OROV symptoms overlap with DENV underscores the need for syndromic diagnostic approach in endemic regions. Continued genomic surveillance and expanded clinical studies are vital to assess long-term consequences. Given OROV\u2019s expanding geographic range, targeted public health measures are essential to mitigate future outbreaks and better understand its pathophysiology.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0013604","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T17:34:58Z","timestamp":1759512898000},"page":"e0013604","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical and laboratory profiles of Oropouche virus disease from the 2024 outbreak in Manaus, Brazilian Amazon"],"prefix":"10.1371","volume":"19","author":[{"given":"Maria Paula","family":"Gomes Mour\u00e3o","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisely Cardoso","family":"de 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