Geneva: World Health Organization, Special Programme for Research and Training in Tropical Diseases, Geneva: 2000. While it has been reported that complications of COVID-19 occur in the second week of illness, the significance of these 2 patterns of fever with regards to the development of complications is unknown [4]. Repeat laboratory investigations and CXR were done for those with prolonged or saddleback fever and collected. Rheumatic fever mostly affects children aged 5-15 years, but it is rare in adults and children aged under 3 years. Interestingly, there are also higher plasma levels of IL-1RA in patients with prolonged fever compared with control patients. Patients with prolonged fever may have had higher levels of IL-1 earlier on before sample collection. Both prolonged (27.8% vs 0.9%, p <0.01) and saddleback fever (14.3% vs 0.9%, p= 0.03) were associated with hypoxia compared to controls. Interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease 2019 (COVID-19). 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). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. -. A more recent article on fever of unknown origin in adults is available. -, Huang C, Wang Y, Li X, et al. Recommendations of the Scientific Working Group on Dengue. Additional searches included the Cochrane database, Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, and the National Guideline Clearinghouse. Cases without prolonged or saddleback fever were included as controls. 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). The average body temperature is 98.6 F (37 C). Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Copyright 2023 American Academy of Family Physicians. 2017 Jun 22;4(3):ofx133. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Careers. Fevers usually don't need treatment. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. If there are no potentially diagnostic clues, the patient should undergo a minimum diagnostic workup, including a complete blood count, chest radiography, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level testing. Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. 2013; 496: 504507. Higher respiratory rate, lower SpO2, and lower systolic BP were also associated with saddleback fever compared with the control group. Additional microbiological investigations, such as blood and urine cultures, influenza and respiratory viral multiplex PCR, dengue NS1 and serology, were ordered at the discretion of the primary treating clinician. Pung R, Chiew CJ, Young BE, et al. 2016 Dec 9;11(12):e0167025. Two of these patients were admitted to the ICU, which may suggest another phenotype of patients who are at higher risk of adverse outcomes. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. The differences in cytokine and chemokine profiles among [the three groups] suggest that different immunological responses could result in the differences in the clinical phenotype observed, said Ng and co-authors. This content is owned by the AAFP. Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. 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 ). bOnly 1 sample of paired values available. Fever duration was longer in patients 6 to 12 months old and 12 to 18 . In addition, IP-10 has also been reported to be associated with increased viral load, lung injury, ICU admission, and mortality [21]. CONCLUSIONS: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. 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]. Published by Oxford University Press on behalf of Infectious Diseases Society of America. Treatment of fever in adults usually involves ibuprofen, acetaminophen, or aspirin. Results: Available at: Wang D, Hu B, Hu C, et al. All authors: no reported conflicts of interest. Before 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. 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. However, ESR does not help discriminate between active autoimmune disease and infection, and malignancies and noninfectious inflammatory diseases can cause an elevated ESR and CRP level. In addition, in comparison with other parameters such as respiratory rate, heart rate, or blood pressure, fever is easy to detect and readily identifiable as a risk factor for severe disease. National Library of Medicine 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. Repeat CXR was not performed for cases in the control group and 1 case of saddleback fever. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19, said the researchers led by Dr Deborah Ng from National Centre for Infectious Diseases (NCID), Singapore, on behalf of the NCID COVID-19 Outbreak Research Team. The analysis, which was. Seven more confirmed cases of novel coronavirus infection in Singapore.2020. In health, body temperature is regulated around a set point of 37 1C, and a circadian temperature rhythm exists in which the highest temperature of each day occurs around 6 p.m. The author(s) received no specific funding for this work. Statistical data analysis on the types of fevers Infect Drug Resist. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue. A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. Both prolonged (27.8% vs 0.9%; P<.01) and saddleback fever (14.3% vs 0.9%; P=.03) were associated with hypoxia compared with controls. Clipboard, Search History, and several other advanced features are temporarily unavailable. Methods: MeSH ; Singapore 2019 Novel Coronavirus Outbreak Research Team. 8600 Rockville Pike The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. Outbreak Research Team members are listed in the Acknowledgments, Deborah H L Ng, Chiaw Yee Choy, Yi-Hao Chan, Barnaby E Young, Siew-Wai Fong, Lisa F P Ng, Laurent Renia, David C Lye, Po Ying Chia, National Centre for Infectious Diseases COVID-19 Outbreak Research Team, Fever Patterns, Cytokine Profiles, and Outcomes in COVID-19, Open Forum Infectious Diseases, Volume 7, Issue 9, September 2020, ofaa375, https://doi.org/10.1093/ofid/ofaa375. 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. Am J Dis Child 1972; 124:544. Prevalence and Predictors of Persistent Symptoms After Clearance of SARS-CoV-2 Infection: A Multicenter Study from Egypt. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Respiratory syncytial virus disease burden in community-dwelling and long-term care facility older adults in Europe and the United States: A prospective study, Viral aetiology and clinical characteristics of acute respiratory tract infections in hospitalized children in Southern Germany (2014-2018), Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People with Treated HIV, Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks, Impact of hypoalbuminemia on ceftriaxone treatment failure in patients with Enterobacterales bacteremia: a propensity matched, retrospective cohort study, About the Infectious Diseases Society of America, https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200430-sitrep-101-covid-19.pdf?sfvrsn=2ba4e093_2, https://www.moh.gov.sg/news-highlights/details/confirmed-imported-case-of-novel-coronavirus-infection-in-singapore-multi-ministry-taskforce-ramps-up-precautionary-measures, https://www.moh.gov.sg/news-highlights/details/seven-more-confirmed-cases-of-novel-coronavirus-infection-in-singapore, https://sso.agc.gov.sg/Act/IDA1976#pr25A-, https://doi.org/10.1101/2020.03.02.20029975, https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-home-care.html, https://www.straitstimes.com/singapore/9-in-10-coronavirus-patients-housed-in-isolation-facilities, https://www.moh.gov.sg/news-highlights/details/56-more-cases-discharged-528-new-cases-of-covid-19-infection-confirmed, http://creativecommons.org/licenses/by-nc-nd/4.0/, Receive exclusive offers and updates from Oxford Academic. -. Oxford University Press is a department of the University of Oxford. In patients with saddleback fever, higher levels of IL-1, IL-21, IL-22, and SDF-1 were observed compared with control patients. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. QJM. 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. 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. A standardized template was used for recording daily signs and symptoms, vital signs, and management. 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. PMC However, unlike RA, rheumatic . However, it is interesting that there are higher pro-inflammatory IL-1 levels in patients with saddleback fever. Heart Lung. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. When compared with controls, both prolonged and saddleback fever were associated with hypoxia, with the highest rate seen in cases with prolonged fever (27.8 percent and 14.3 percent vs 0.9 percent for prolonged and saddleback fever vs control, respectively; p<0.01 and p=0.03 for each respective comparison). Symptoms of RSV include runny nose, cough, fever, and . Cytokine level for healthy controls (n=23) is indicated by the black dotted line. doi: 10.1371/journal.pntd.0004575. Laboratory Results for Prolonged and Saddleback Fever. 2021 Jan-Feb;50(1):28-32. doi: 10.1016/j.hrtlng.2020.10.013. PLoS Negl Trop Dis. Several diagnostic algorithms have been suggested for FUO, but few are supported by evidence from prospective studies.17 Region-specific serologic tests, more advanced radiologic studies, and more invasive diagnostic procedures can be guided by potentially diagnostic clues. COVID-19; cytokines; fever; prolonged; saddleback. Normal body temperature can vary depending on the individual, the time of day, and even the weather. Background: An official website of the United States government. Before Epub 2022 Aug 11. 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. Open Forum Infect Dis. 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] . Challenges in dengue fever in the elderly: Atypical presentation and risk of severe dengue and hospital-acquired infection. The results of this study can be used to optimize placement of patients with COVID-19. It starts suddenly and lasts 3 to 5 days. Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. 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). Both prolonged (27.8% vs 0.9%; P < .01) and saddleback fever (14.3% vs 0.9%; P = .03) were associated with hypoxia compared with controls. A more recent qualitative definition requires only a reasonable diagnostic evaluation. 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. Please enable it to take advantage of the complete set of features! 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. 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]. The elevation of circulating IL-1RA may reflect overactive IL-1 activation, which has been reported to associated with severe outcomes in COVID-19 [24]. Note that serologic tests are helpful only if there are potentially diagnostic clues and if the patient lives in or has visited an area where the suspected disease is prevalent.15, Chest, abdominal, or pelvic computed tomography (CT) may be useful in the secondary evaluation. When compared with controls, both prolonged and saddleback fever were associated with hypoxia, with the highest rate seen in cases with prolonged fever (27.8 percent and 14.3 percent vs 0.9 percent for prolonged and saddleback fever vs control, respectively; p<0.01 and p=0.03 for each respective comparison). For cases with saddleback fever, fever recurred at a median (IQR) of 10 (812) days after symptom onset. 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