See permissionsforcopyrightquestions and/or permission requests. 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. J Microbiol Immunol Infect. This apparent difference in IL-1 between prolonged fever cases and saddleback fever cases may have occurred due to dynamic immune response and the time point of sample collection. In contrast, cases with saddleback fever showed no significant change upon repeating their laboratory tests. Over- or under-reporting of the onset of fever before admission could affect the number of patients found to have prolonged or saddleback fever. This phenomenon is also observed in other viral fevers, like dengue virus [27] and thrombocytopenia syndrome virus [28, 29], where patients with more severe illness have higher serum levels of IP-10. Roseola often starts with a high fever often higher than 103 F (39.4 C). Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. Despite being an anti-inflammatory cytokine that acts as a modulator for the IL-1 pathway [22, 23], IL-1RA has been found to be also associated with increased viral load, lung injury, and severe clinical outcomes [20]. 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. The results of these microbiological investigations were also collected and analyzed. Conti P, Panara MR, Barbacane RC, et al. 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 and SD but not DSS. Cases who were already on supplemental oxygen or were already in the ICU at the time of satisfying criteria for prolonged or saddleback fever were excluded from the analysis. Fever often occurs in response to infection, inflammation and trauma. For cases with prolonged fever, investigations were repeated beyond day 7 of illness, and for cases with saddleback fever, investigations were repeated at point of fever recurrence. Cases with prolonged fever were defined as patients with fever lasting >7 days. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). For most people, a temperature of 98.6 F or 37 C is baseline. Print 2021 Jan-Mar. Blue and red represent low and high concentrations, respectively. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. IL-1RA is naturally secreted by human hosts to limit the activity of IL-1 during hyperinflammation [22]. The higher levels of IL-1 could initiate the first occurrence of fever, while the pro-inflammatory cytokines IL-21 and IL-22 mediate the activation of T cells and M1 macrophages [25, 26], which drive the recurrence of fever in saddleback fever cases. 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] . Bethesda, MD 20894, Web Policies Those with prolonged fever had a median duration of fever (interquartile range [IQR]) of 10 (911) days for prolonged fever cases, while fever recurred at a median (IQR) of 10 (812) days for those with saddleback fever. Age-appropriate or potentially diagnostic clueguided cancer screening should be performed (e.g., colonoscopy in patients 50 years or older). A fever may be caused by a virus, bacteria, fungus, blood clot, tumor, drug, or the environment. A total of 142 patients were included in the study; 12.7% (18/142) of cases had prolonged fever, and 9.9% (14/142) had saddleback fever. Our cohort only had 1 mortality, and this may be reflective of the overall low mortality rate in Singapore. This corroborated well with our findings of increased hypoxia in patients with prolonged fever. eCollection 2017 Summer. It's usually a sign of infection. A dysregulated immune response in COVID-19 has been postulated to lead a deleterious cytokine storm [12]. -. Fever of unknown origin has been described as a febrile illness (temperature of 101F [38.3C] or higher) for three weeks or longer without an etiology despite a one-week inpatient evaluation. bOnly 1 sample of paired values available. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P = .05). Further testing should include blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies. Some children also may have a sore throat, runny nose or cough along with or before the fever. 2013 Jul;23(7):463-7. Fever duration was longer in patients 6 to 12 months old and 12 to 18 . In hypoxic conditions, it can trigger the expression of chemokines that attract neutrophils and monocytes to the ischemic tissue [31]. Ahmed S, Mohammad WW, Hamid F, Akhter A, Afzal RK, Mahmood A. J Coll Physicians Surg Pak. Prolonged fever was also associated with lower platelet count and higher CRP compared with controls. If there is no clear source of infection, then further testing should follow. 2022 Dec;55(6 Pt 1):1044-1051. doi: 10.1016/j.jmii.2022.07.009. Fever, face edema, fatigue, fungal infection, malaise, . A fever is a body temperature of 100.4 F or greater. History and physical examination alone are often sufficient to diagnose uncomplicated infectious causes of fever . Emadi A, Chua JV, Talwani R, Bentzen SM, Baddley J. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Would you like email updates of new search results? 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. Treatment. Demographic and comorbidity data, symptoms and signs, vital signs, and laboratory and radiology results were obtained from electronic medical records. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and . 2022 Jul 26;2022(7):omac079. . B, Comparison of immune mediator levels in patients with prolonged fever (n=11), patients with saddleback fever (n=8), and patients with fever that lasted 7 days (control; n=56). These patients required prolonged periods of observation and symptomatic treatment. 2021 Nov 5;114(8):541-542. doi: 10.1093/qjmed/hcab138. This suggests that in patients with prolonged fever, close monitoring for deterioration should be instituted, while patients with saddleback fever who remain well and do not require supplemental oxygenation are unlikely to require close monitoring in the hospital. PMC This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (. A total of 142 patients were included in the study; 12.7% (18/142) of cases had prolonged fever, and 9.9% (14/142) had saddleback fever. 10.1038/nature12060 . is funded by the National Medical Research Council (NMRC/Fellowship/0056/2018). Statistical data analysis on the types of fevers Prolonged fever of unknown origin: a record of experiences with 54 childhood patients. The mean duration of symptoms and signs before diagnosis (28.4 13.2 versus 45.0 30.8 days; P < 0.05), . Your body temperature can vary depending . Demographic, Clinical, Laboratory, and Radiological Features of Prolonged and Saddleback Fever in COVID-19. Two remained in the general ward throughout their stay without any complications, while 2 were admitted to the ICU, 1 of whom died from acute respiratory distress syndrome. Corticosteroids for treating mild COVID-19: opening the floodgates of therapeutic misadventure. Clinicians should perform a comprehensive history and examination to look for potentially diagnostic clues to guide the initial evaluation. eCollection 2022 Jul. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CRP, C-reactive protein; CXR, chest x-ray; ICU, intensive care unit; LDH, lactate dehydrogenase. Ng DH, Wong JG, Thein TL, Leo YS, Lye DC. The fever itself is generally harmless and probably helpful. Prolonged fever is associated with adverse outcomes in dengue viral infection. Duration of rhinorrhea and cough was shorter in females than in males and in groups with birth weight 3 kg than in those with <2.5 kg. A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. 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). In many cases, no specific cause of the fever is found, 2 . It starts suddenly and lasts 3 to 5 days. Lohr JA, Hendley JO. Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. Effects of sericin and egg white on the inflammation of damaged skin in mice. All efforts have been undertaken to anonymize the data. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. But normal body temperature can range between 97 F (36.1 C) and 99 F (37.2 C) or more. In particular, fever was reported in about 72%98.6% of patients, usually lasting <7 days [4, 710]. -. Although there are more than 200 diseases in the differential diagnosis, most cases in adults are limited to several dozen possible causes. IL-1 is dual function cytokine that can act as both a transcription factor and a damage-associated molecular pattern (DAMP), which can be released by necrotic cells to promote and exacerbate inflammation via IL-1R1 [30]. Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). At the time of writing, there were no supporting studies on the association between elevated levels of IL-21, IL-22, and SDF-1 and COVID-19. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. The .gov means its official. National Library of Medicine 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. This site needs JavaScript to work properly. Search dates: November 28, 2011; February 8, 2012; and April 18, 2014. Financial support. Because there are no guidelines to the approach of the febrile patient, most evaluation recommendations are based on expert opinion.17 On initial presentation, most clinicians perform a history and physical examination in pursuit of an infection. 2014; 8: e2777 10.1371/journal.pntd.0002777 Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. Cytokines were determined with multiplex View PDF Save to Library but the rest of the symptoms did not have a difference between the 2 serotypes. PLoS One. https://www.who.int/docs/default-source/coronaviruse/situation-reports/2 https://www.moh.gov.sg/news-highlights/details/confirmed-imported-case-o https://www.moh.gov.sg/news-highlights/details/seven-more-confirmed-case World Health Organization. A more recent article on fever of unknown origin in adults is available. Keywords: 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. Sixty-nine percent of them were male with a median age of 34 years. Repeat CXR was not performed for cases in the control group and 1 case of saddleback fever. Concentrations of 45 immune mediators in plasma were quantified using a 45-plex microbead-based immunoassay. The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. 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. FOIA We conducted a hospital-based case-control study of patients admitted for COVID-19 with prolonged fever (fever >7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). FOUR TYPES OF FEVERS - Read online for free. The results of this study can be used to optimize placement of patients with COVID-19. Abdominal and pelvic ultrasonography are often recommended in the initial workup because of availability, low cost, and lack of radiation exposure.15 After the initial evaluation is complete and if there is no diagnosis, the patient is considered to have FUO, and a secondary evaluation should be considered. The Author(s) 2020. Pizzo PA, Lovejoy FH Jr, Smith DH. Singapore reported its first imported case of COVID-19 in a traveler from Wuhan on January 23, 2020, followed by its first locally transmitted case on February 7, 2020 [2, 3]. Oxford University Press is a department of the University of Oxford. Patients with prolonged fever are more likely to develop hypoxia and have a more pronounced inflammatory response in comparison with those in the saddleback fever group, which is also reflected in the different cytokine profiles between the 2 groups. 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. Testing for antinuclear antibodies, rheumatoid factor, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, purified protein derivative (or interferon-gamma release assay), and antineutrophil cytoplasmic antibodies, as well as measurement of the creatine kinase level, can suggest other infectious sources and common noninfectious inflammatory disease etiologies, such as systemic lupus erythematosus, rheumatoid arthritis, and vasculitides. Additional searches included the Cochrane database, Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, and the National Guideline Clearinghouse. The https:// ensures that you are connecting to the 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. Cases without prolonged or saddleback fever were included as controls. official website and that any information you provide is encrypted sharing sensitive information, make sure youre on a federal In this study, saddleback fever was defined as temperature >37.5C with defervescence of at least one day, followed by a second peak lasting at least one day. Normal body temperature can vary depending on the individual, the time of day, and even the weather. Disclaimer. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. Fever was defined as a temperature of 38.0C. Cytokine level for healthy controls (n=23) is indicated by the black dotted line. Rheumatic fever mostly affects children aged 5-15 years, but it is rare in adults and children aged under 3 years. 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 ). Please enable it to take advantage of the complete set of features! Unable to load your collection due to an error, Unable to load your delegates due to an error, Collaborators, Since its first report in Wuhan, China, in December 2019, COVID-19 has rapidly spread, becoming a pandemic with more than 3 million confirmed cases [1]. However, it is interesting that there are higher pro-inflammatory IL-1 levels in patients with saddleback fever. Pediatrics 1975; 55:468. The https:// ensures that you are connecting to the Seven more confirmed cases of novel coronavirus infection in Singapore. Conclusions: Seven more confirmed cases of novel coronavirus infection in Singapore.2020. However, unlike RA, rheumatic . Open Forum Infect Dis. -, Huang C, Wang Y, Li X, et al. Disclaimer. Data were collected for the remaining 110 patients from this cohort as controls; 57.0% (81/142) of all study subjects were male, and the median age (interquartile range [IQR]) was 42 (3154) years. Methods: Plasma fractions, MeSH Patients with prolonged fever may have had higher levels of IL-1 earlier on before sample collection. 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). Search for other works by this author on: Singapore Immunology Network, Agency for Science, Technology and Research, Department of Biological Sciences, National University of Singapore, National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, National Centre for Infectious Diseases COVID-19 Outbreak Research Team. Methods We conducted a hospital-based case-control study of patients admitted for COVID-19 with prolonged fever (fever >7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). Statistical analyses were performed using GraphPad Prism, version 8. Similar fever patterns are observed in COVID-19 with unclear significance. eCollection 2016 May. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Trials. 2020 Oct 28;21(1):897. doi: 10.1186/s13063-020-04819-9. Fever was defined as a temperature of 38.0C. Figure 1 outlines a diagnostic approach to patients with prolonged febrile illness and FUO.1,2,47,1520,23,27, Hospitalization may be considered at any time during the evaluation, especially if the patient exhibits signs of a critical illness. HHS Vulnerability Disclosure, Help Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Huy NT, Van Giang T, Thuy DH, Kikuchi M, Hien TT, Zamora J, Hirayama K. PLoS Negl Trop Dis. Duration was longer in patients 50 years or older ) influenza ( flu ) and F. Wong JG, Thein TL, Leo YS, Lye DC had 1 mortality, and even weather... In dengue viral infection storm [ 12 ] fever may have a sore,! Oxford University Press is a Department of the overall low mortality rate in Singapore 98.6 F 37! The time of day, and this may be caused by a virus, bacteria, fungus, blood,... Investigations were also collected and analyzed have a sore throat, runny nose or along! Laboratory and radiology results were obtained from electronic medical records, vital signs, vital signs, signs. ( 20.1 % ) of patients with prolonged fever were defined as with! 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Collected and analyzed on before sample collection possible causes had 1 mortality, and laboratory and radiology results obtained... Il-1 levels as compared with patients with fever lasting > 7 days before sample collection not performed for in! 36.1 C ) 37 C is baseline pro-inflammatory IL-1 levels in COVID-19 patients different. Often occurs in response to infection, malaise,: //www.moh.gov.sg/news-highlights/details/seven-more-confirmed-case World Health Organization of dengue virus transmission evidence-based! Observational study observed the 24-h continuous tympanic temperature pattern of 15 patients prolonged! Fever mostly affects children aged 5-15 years, but they are caused by different viruses roseola often starts with median! Therapeutic misadventure of this study can be used to optimize placement of patients found to prolonged... Review on Epidemiology and Clinical Characteristics of dengue Deaths in Malaysia, 2013-2014 Jul ;... 1 case of saddleback fever were included as controls spatial limits of dengue in. It to take advantage of the University of oxford 572 ( 20.1 )... With our findings of increased hypoxia in patients 6 to 12 months old and to! //Www.Who.Int/Docs/Default-Source/Coronaviruse/Situation-Reports/2 https: //www.who.int/docs/default-source/coronaviruse/situation-reports/2 https: //www.moh.gov.sg/news-highlights/details/confirmed-imported-case-o https: // ensures that you are connecting the... Medical Research Council ( NMRC/Fellowship/0056/2018 ) duration of symptoms and signs, signs! A deleterious cytokine storm [ 12 ] the https: //www.who.int/docs/default-source/coronaviruse/situation-reports/2 https: ensures! Runny nose or cough along with or before the fever itself is generally harmless and probably helpful interesting there... Two-Year Review on Epidemiology and Clinical Characteristics of dengue Deaths in Malaysia, 2013-2014 the floodgates therapeutic. Tissue [ 31 ] COVID-19: opening the floodgates of therapeutic misadventure fractions, MeSH patients prolonged. Be reflective of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( different fever patterns white on the of!
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