JAMA Intern Med. Biphasic Zika Illness With Rash and Joint Pain. https://www.moh.gov.sg/content/moh_web/home/Publications/Reports/2006/co http://www.who.int/tdr/publications/documents/dengue-swg.pdf, Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Joen AG, et al. There were no significant changes in laboratory findings when repeated at the point of fever, except for a rise in platelet and lymphocyte counts (Table 2). Notably, in a study of 3 COVID-19 patients, peak IL-1 appeared to precede the nadir of lung function [33], which may herald worsening inflammation. is funded by the National Medical Research Council (NMRC/Fellowship/0056/2018). For full access to this pdf, sign in to an existing account, or purchase an annual subscription. To our knowledge, this is the first study to examine the association between the patterns of fever and outcomes in COVID-19. doi: 10.1371/journal.pone.0167025. Potential conflicts of interest. Print 2021 Jan-Mar. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. The different prognoses for these 2 groups of patients have implications for the distribution of increasingly burdened hospital resources given the exponential rise in cases worldwide. Careers. Another 4 patients were excluded from the primary analysis as they had a saddleback pattern of fever that lasted >24 hours; 12.7% (18/142) of cases had prolonged fever and another 9.9% (14/142) had saddleback fever. Ying-Hao P, Yuan-Yuan G, Hai-Dong Z, Qiu-Hua C, Xue-Ran G, Hai-Qi Z, Hua J. Communicable Diseases Surveillance in Singapore 2005. Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. Saddleback fever was present in 165 (5.8%). Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Conti P, Panara MR, Barbacane RC, et al. CONCLUSIONS: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Copyright 2023 MIMS Pte Ltd. All rights reserved. Angela Chow Li Ping, Brenda Sze Peng Ang, Chen Seong Wong, Cheng Chuan Lee, Ding Ying, Jun-Yang Tay, Kalisvar Marimuthu, Lawrence Soon U. Lee, Yee-Sin Leo, Li Min Ling, Li Wei Ang, Lin Cui, Mark I-Cheng Chen, Monica Chan, Mucheli Sharavan Sadasiv, Oon-Tek Ng, Pei Hua Lee, Poh Lian Lim, Sapna Pradip Sadarangani, Shawn Vasoo, Stephanie Sutjipto, Tsin Wen Yeo, Tze Minn Mak. For cytokine profiling, the Mann-Whitney U test was applied to ascertain significant differences in immune mediator levels between patients experiencing different fever patterns. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (. If there is no clear source of infection, then further testing should follow. Cytokines included granulocyte-macrophage colony-stimulating factor (GM-CSF), epidermal growth factor (EGF), brain-derived neurotrophic factor, beta-nerve growth factor (bNGF), basic fibroblast growth factor (FGF-2), hepatocyte growth factor (HGF), monocyte chemoattractant protein (MCP) 1, macrophage inflammatory protein (MIP) 1, MIP-1, RANTES (regulated on activation, normal T cell expressed and secreted), chemokine (C-X-C motif) ligand (CXCL) 1 (GRO-), stromal cellderived factor 1 (SDF-1), interferon (IFN) gamma-induced protein 10 (IP-10), eotaxin, IFN-, IFN-, interleukin (IL) IL-1, IL-1, IL-1 receptor agonist (IL-1RA), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, leukemia inhibitory factor (LIF), stem cell factor (SCF), tumor necrosis factor (TNF-), TNF-, vascular endothelial growth factors A and D (VEGF-A, VEGF-D), platelet-derived growth factor (PDGF-BB), and placental growth factor (PLGF-1). Saddleback fever was significantly associated with hypoxia (14.3% vs 0.9%; P=.03) but not ICU admission (0.9% vs 0.0 %; P=1.00) compared with those in the control group. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. The Wilcoxon signed-rank test was used to evaluate for differences in paired samples. 2020 Oct 28;21(1):897. doi: 10.1186/s13063-020-04819-9. Comparing the difference between prolonged fever cases and saddleback fever cases, we found an increased IL-1 level and lower IP-10 level on admission. 2013 Sep 26;7(9):e2412. 2013 Jul;23(7):463-7. The Author(s) 2020. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Trials. Home or community isolation facilities are commonly used globally for less sick patients such that hospital beds are free up to cater for sicker patients. All efforts have been undertaken to anonymize the data. Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever. 2 A diagnosis of classic KD is made in patients with prolonged fever (five or more days) and four or more of the following principal . Cases with prolonged fever were defined as patients with fever lasting >7 days. Eleven patients with prolonged fever, 8 patients with saddleback fever and 56 patients with fever lasting 7 days (controls) were evaluated at the first time point of blood sample collection upon hospitalization (median of 6 days postillness onset) (Figure 1A). Cases with saddleback fever were defined as patients with recurrence of fever lasting <24 hours, after defervescence, beyond day 7 of illness. There are no published guidelines, nor is there a recommended standard approach to the diagnosis. However, there was a proportion of patients from our hospital who displayed 2 patterns of fever: 1 group had fever persisting into the second week of illness, while the second group displayed a saddleback pattern of fever, similar to that previously observed in dengue [11]. Those with prolonged fever had a median duration of fever for 10 days (IQR 9-11 days) for prolonged fever cases, while fever recurred at a median of 10 days (IQR 8-12 days) for those with saddleback fever. Laboratory Results for Prolonged and Saddleback Fever. The https:// ensures that you are connecting to the Would you like email updates of new search results? Higher heart rate and respiratory rate and lower oxygen saturation (spO2), systolic and diastolic blood pressure (BP) were associated with prolonged fever compared with controls (Table 1). Huy NT, Van Giang T, Thuy DH, Kikuchi M, Hien TT, Zamora J, Hirayama K. PLoS Negl Trop Dis. Academic Pulmonary Sleep Medicine Physician Opportunity in Scenic Central Pennsylvania, Academic Surgical Pathologist/Breast Pathologist, Copyright 2023 Infectious Diseases Society of America. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Approval for data collection by retrospective chart review with a waiver of written informed consent from study participants was granted by the Singapore Ministry of Health under the Infectious Diseases Act as part of the outbreak investigation [14]. Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Before In addition to their pro-inflammatory properties, both IL-6 and IP-10 have been reported to be associated with disease severity and ICU admission in COVID-19 [18, 19] . Accessibility Patients with prolonged fever had higher induced protein -10 and lower interleukin-1 levels compared with those with saddleback fever at the early acute phase of disease. Department of Infectious Diseases, Tan Tock Seng Hospital, Correspondence: Deborah H. L. Ng, MBChB, MRCP(UK), MSc, MPH, Department of Infectious Diseases, Centre for Healthcare Innovation, 18 Jalan Tan Tock Seng, Singapore 308443 (. We wish to thank members of the Singapore Immunology Network Wilson How, Norman Leo Fernandez, Olaf Rtzschke, and Bernett Lee for their assistance with the multiplex microbead-based immunoassays and data analyses. Human immunodeficiency virus and appropriate region-specific serologic testing (e.g., cytomegalovirus, Epstein-Barr virus, tuberculosis) and abdominal and pelvic ultrasonography or computed tomography are commonly performed. Khalaf M, Alboraie M, Abdel-Gawad M, Abdelmalek M, Abu-Elfatth A, Abdelhamed W, Zaghloul M, ElDeeb R, Abdeltwab D, Abdelghani M, El-Raey F, Aboalam H, Badry A, Tharwat M, Afify S, Elwazzan D, Abdelmohsen AS, Fathy H, Wagih Shaltout S, Hetta HF, Bazeed SE. Geneva: World Health Organization, Special Programme for Research and Training in Tropical Diseases, Geneva: 2000. Rheumatic fever mostly affects children aged 5-15 years, but it is rare in adults and children aged under 3 years. Concentrations of 45 immune mediators in plasma were quantified using a 45-plex microbead-based immunoassay. Both prolonged fever and saddleback fever were not significantly associated with mechanical ventilation as compared with the control group (Table 1). In this study, we aim to examine the characteristics of patients who developed these patterns of fever and their correlation to cytokine levels, as well as the association with adverse outcomes in COVID-19. Symptoms of RSV include runny nose, cough, fever, and . Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. Bethesda, MD 20894, Web Policies Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. 2016 Dec 9;11(12):e0167025. doi: 10.1371/journal.pntd.0004575. Demographic and comorbidity data, symptoms and signs, vital signs, and laboratory and radiology results were obtained from electronic medical records. Interestingly, there are also higher plasma levels of IL-1RA in patients with prolonged fever compared with control patients. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Edupuganti S, Natrajan MS, Rouphael N, Lai L, Xu Y, Feldhammer M, Hill C, Patel SM, Johnson SJ, Bower M, Gorchakov R, Berry R, Murray KO, Mulligan MJ. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. Factors associated with dengue shock syndrome: a systematic review and meta-analysis. McClung HJ. Cases with prolonged fever were more likely to have hypoxia (27.8% vs 0.9%; P<.01) and ICU admission (11.1% vs 0.9%; P=.05) compared with cases in the control group (Table 1). PMC Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are nonspecific acute-phase reactants that are routinely part of the evaluation of febrile patients.5,28 An extremely elevated ESR (100 mm per hour or greater) suggests etiologies such as abdominal or pelvic abscess, osteomyelitis, and endocarditis. eCollection 2013. [The] lower IP-10 level [with saddleback fever] is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases, they noted. Similar fever patterns are observed in COVID-19 with unclear significance. Keywords: For cases with saddleback fever, fever recurred at a median (IQR) of 10 (812) days after symptom onset. COVID-19; cytokines; fever; prolonged; saddleback. Federal government websites often end in .gov or .mil. PLoS Negl Trop Dis. Bookshelf Effects of sericin and egg white on the inflammation of damaged skin in mice. Copyright 2023 American Academy of Family Physicians. Approximately 12% to 35% of patients die from an FUO-related cause (generally infection or malignancy), yet of those whose conditions remain undiagnosed, most recover or have a benign course with a good prognosis.5,22. A fever is a body temperature of 100.4 F or greater. Prolonged fever was also associated with lower platelet count and higher CRP compared with controls. Patients with prolonged fever had higher induced protein10 and lower interleukin-1 levels compared with those with saddleback fever at the early acute phase of disease. Common causes of FUO are listed in Table 2.6,1523 Typical subgroups used in the differential for classical FUO are infection (20% to 40%), malignancy (20% to 30%), noninfectious inflammatory diseases (10% to 30%), miscellaneous (10% to 20%), and undiagnosed (up to 50%).1,46,1418,2224 Noninfectious inflammatory diseases commonly include connective tissue diseases, vasculitides, and granulomatous diseases.16,17 In developed countries, the noninfectious inflammatory diseases and undiagnosed groups comprise a higher proportion of FUO cases.5,10,15,17 Underdeveloped countries have higher rates of infection and neoplasm.6,24 Drug fever is implicated in 1% to 3% of FUO cases16 (Table 320,21,25,26 ). 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