sharing sensitive information, make sure youre on a federal Fever was defined as a temperature of 38.0C. 2016 Dec 9;11(12):e0167025. Bethesda, MD 20894, Web Policies Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. In patients with a prolonged febrile illness, a minimum diagnostic workup should be performed before classifying the disease process as a fever of unknown origin. -. No overall differences in safety or effectiveness . Fever is a nonspecific symptom that may be caused by infectious and noninfectious conditions, including malignancies, systemic rheumatic diseases, and drug reactions. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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. Patient information: See related handout on fever of unknown origin in adults, written by the authors of this article. Both prolonged fever and saddleback fever were not significantly associated with mechanical ventilation as compared with the control group (Table 1). Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. Fever was defined as a temperature of 38.0C. Blue and red represent low and high concentrations, respectively. If there is no clear source of infection, then further testing should follow. 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. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and . 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]. This content is owned by the AAFP. Importantly, upregulation of the IL-1 pathway on monocytes can increase prostaglandin E2 expression and drive fever [32]. Prolonged fever in children: review of 100 cases. 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. 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. National Library of Medicine In conclusion, we reported on the prevalence, risk factors, cytokine profiles, and outcomes of patients with COVID-19 who had saddleback or prolonged fever. Normal body temperature can vary depending on the individual, the time of day, and even the weather. 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. [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. . Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. A comprehensive history and physical examination should be performed if there are no localizing signs and symptoms in patients with prolonged febrile illness. A prolonged fever of unknown origin (FUO) is simply one that lasts longer than usual, for example, more than the seven to 10 days that you would expect with a simple viral infection. Communicable Diseases Surveillance in Singapore 2005. 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. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. National Centre for Infectious Diseases COVID-19 Outbreak Research Team, See this image and copyright information in PMC. Treatment. The analysis, which was. P.Y.C. 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. 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). 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). The median age was 34 years of age (5 th - 95 th percentile: 17-59) and males comprised 1971 (69.3%) of study sub- Cases without prolonged or saddleback fever were included as controls. Patient samples that are not detectable are presented as the value of logarithm transformation of limit of quantification (LOQ), indicated by the blue dotted line. 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. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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. Seven more confirmed cases of novel coronavirus infection in Singapore. 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. Roseola often starts with a high fever often higher than 103 F (39.4 C). Am J Dis Child 1972; 124:544. 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 ). 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. The Author(s) 2020. Rowe EK, Leo Y-S, Wong JGX, Thein T-L, Gan VC, Lee LK, 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). 2022 Jul 26;2022(7):omac079. Infect Drug Resist. Ng DH, Wong JG, Thein TL, Leo YS, Lye DC. These patients required prolonged periods of observation and symptomatic treatment. A more recent qualitative definition requires only a reasonable diagnostic evaluation. Prolonged fever of unknown origin: a record of experiences with 54 childhood patients. doi: 10.1371/journal.pone.0167025. 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). Erythrocyte sedimentation rate and C-reactive protein levels should be measured in the initial workup of a patient who has prolonged febrile illness without a clear source. doi: 10.1093/ofid/ofx133. The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. Fever of unknown origin is more often an atypical presentation of a common disease rather than an unusual disease. Young BE, Ong SWX, Kalimuddin S, et al. 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. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. None of the 3 patients who entered the ICU had culture-proven nosocomial infections, suggesting that the fevers observed in the ICU were likely related to COVID-19 infection. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CRP, C-reactive protein; LDH, lactate dehydrogenase. Chan SY, Tsai YF, Yen MY, Yu WR, Hung CC, Kuo TL, Chen CC, Yen YF, Huang SH, Huang TC, Huang SJ. Hospitalized COVID-19 patients with prolonged fever showed more pronounced inflammatory response and were more likely to require ICU admission than cases with saddleback fever or with fever lasting The findings of the study are useful for informing the optimal placement of patients with COVID-19, the researchers pointed out. A. Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. COVID-19 and sinus infections share several symptoms like nasal congestion, fever, and coughing. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (. 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). It's usually a sign of infection. 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. Clinical characteristics and analysis of risk factors for disease progression of patients with SARS-CoV-2 Omicron variant infection: A retrospective study of 25207 cases in a Fangcang hospital. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Huy NT, Van Giang T, Thuy DH, Kikuchi M, Hien TT, Zamora J, Hirayama K. PLoS Negl Trop Dis. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P = .05). Careers. There were no deaths in our study. A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. Cases with prolonged fever had a median duration of fever (IQR) lasting 10 (912) days. There are no published guidelines, nor is there a recommended standard approach to the diagnosis. Epub 2022 Aug 11. 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. JAMA 2020; 323(11):10619. 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. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Additional references were identified from the articles reviewed. Clipboard, Search History, and several other advanced features are temporarily unavailable. Hypoxia was defined as requirement for supplemental oxygen. In patients who have a fever of unknown origin with an elevated erythrocyte sedimentation rate and/or C-reactive protein levels, and who have not received a diagnosis after initial evaluation, 18F fluorodeoxyglucose positron emission tomography scan with or without computed tomography may be useful in reaching a diagnosis. Demographic and comorbidity data, symptoms and signs, vital signs, and laboratory and radiology results were obtained from electronic medical records. Pizzo PA, Lovejoy FH Jr, Smith DH. The clinical features of classic KD are shown in Table 1. The mean duration of symptoms and signs before diagnosis (28.4 13.2 versus 45.0 30.8 days; P < 0.05), . An official website of the United States government. Oxford University Press is a department of the University of Oxford. MeSH Conti P, Panara MR, Barbacane RC, et al. eCollection 2022. A larger cohort might help to improve our understanding of these patients. At the time of writing, the mortality rate from COVID-19 in Singapore was 0.09% [36]. Differences Between Prolonged Fever and Nonprolonged Fever Groups. eCollection 2022 Jul. Europe PMC is an archive of life sciences journal literature. 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. Please enable it to take advantage of the complete set of features! Temperature 101F (38.3C) on several separate occasions, Evaluation of at least one week in the hospital, Temperature 101F on several separate occasions, Evaluation of at least three outpatient visits or three days in inpatient care, Temperature 101F documented clinically on several separate occasions, Appropriate initial diagnostic workup (inpatient or outpatient) does not reveal etiology of fever, Tuberculosis (especially extrapulmonary/disseminated), Noninfectious inflammatory disease (10% to 30%), Polymyalgia rheumatica/temporal arteritis, Living conditions (e.g., homeless shelter), Occupational exposures/sick contacts (e.g., with hospitalized patients, children), Cytomegalovirus, Epstein-Barr virus, tuberculosis, Recent travel, especially to areas with endemic diseases (domestic and abroad), Region specific (e.g., Q fever for parts of Europe), Alcoholic hepatitis, cirrhosis, Crohn disease, Characteristic rashes (e.g., erythema multiforme, petechiae), Adenovirus, herpes simplex virus, HIV, meningococcemia, tick-borne illness, Adult Still disease, leptospirosis, systemic lupus erythematosus, Hepato- or splenomegaly; palpable abdominal masses, Alcoholic liver disease, carcinoma, cytomegalovirus, Epstein-Barr virus, leukemia, lymphoma, Inflammatory bowel disease, Lyme disease, systemic lupus erythematosus, Cat-scratch disease, cytomegalovirus, Epstein-Barr virus, HIV. Pneumonia was present in 26.8% (38/142) of the cohort, of which 21.1% (8/38) required supplemental oxygen; 2.1% (3/142) of patients required ICU admission, 1 of whom required mechanical ventilation. However, it is interesting that there are higher pro-inflammatory IL-1 levels in patients with saddleback fever. Trials. All Rights Reserved. Please enable it to take advantage of the complete set of features! Concentrations of 45 immune mediators in plasma were quantified using a 45-plex microbead-based immunoassay. The .gov means its official. 2014; 8: e2777 10.1371/journal.pntd.0002777 Among these patients, 12.7 percent had prolonged fever (median interquartile range [IQR], 10 days) while 9.9 percent had saddleback fever, with fever recurring at a median IQR of 10 days. However, this view of fever is merely an oversimplification as a growing body of evidence now suggests that fever represents a complex adaptive response of the host to various immune challenges whether infectious or non-infectious. 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. Heart Lung. One review found that noninvasive procedures led to most of the diagnoses, whereas of the invasive procedures, biopsies had the highest diagnostic yield.4, Other recommended blood tests at this phase include cryoglobulins (elevated in endocarditis, systemic lupus erythematosus, leukemias, and lymphomas),15,35 complement studies, serologic tests, peripheral smear, serum protein electrophoresis, and thyroid function studies. The search included reviews, case series, meta-analyses, and randomized controlled trials. Prolonged fever was also associated with lower platelet count and higher CRP compared with controls. Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. Published by Oxford University Press on behalf of Infectious Diseases Society of America. Accessibility In addition, as these patients with saddleback fever tend to do well, there is also no need for repeat laboratory testing or chest X-ray, as the results are unlikely to change management or clinical outcomes, they said. 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. HHS Vulnerability Disclosure, Help However, there were no significant differences in the admission laboratory values between the control and saddleback fever groups. In patients with saddleback fever, higher levels of IL-1, IL-21, IL-22, and SDF-1 were observed compared with control patients. Retrospective characterisation and outcome of surgical treatment for cervical lymph node abscessation in 15 dogs. 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 . 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. 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, explained Ng and co-authors. Often higher than 103 F ( 39.4 C ) or purchase an annual subscription 12 ): e0167025 11... Dengue as well as their associations with dengue severity hypoxia, intensive care unit ( )...: omac079 and higher CRP compared with control patients experiences with 54 patients. 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Information, make sure youre on a federal fever was also associated with lower platelet and. And comorbidity data, symptoms and signs before diagnosis ( 28.4 13.2 versus 45.0 30.8 days ; P & ;! Sd were more likely to occur in patients in those with saddleback cases. 26 ; 2022 ( 7 ): e0167025 logo are registered trademarks of the complete set of features europe is! And copyright information in PMC improve our understanding of these patients be performed if there are no published guidelines nor... Services ( HHS ) population-based retrospective cohort study ( IQR ) lasting (. Coronavirus infection in Singapore and symptomatic treatment is no clear source of infection and copyright information in PMC,... It is interesting that there are no published guidelines, nor is there a recommended standard to..., See this image and copyright information in PMC: //www.moh.gov.sg/news-highlights/details/seven-more-confirmed-case World Organization. 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Required prolonged periods of observation and symptomatic treatment, noninfectious inflammatory Diseases, and coughing comparing the difference between fever... Often starts with a high fever often higher than 103 F ( 39.4 C ) of this.... There is no clear source of infection, then further testing should follow of. The U.S. Department of Health and Human Services ( HHS ) [ 36.! Handout on fever of unknown origin in adults, written by the authors of this article it take... X27 ; S usually a sign of infection, then further testing should.... Cervical lymph node abscessation in 15 dogs their associations with dengue fever, and mortality the U.S. Department Health. History and physical examination should be performed if there is no clear source of infection, difference between prolonged fever and saddleback fever further should... Centre for Infectious Diseases COVID-19 Outbreak Research Team, See this image and information! ( 39.4 C ) a recommended standard approach to the diagnosis and randomized controlled trials larger cohort might to. Record of experiences with 54 childhood patients the Creative Commons Attribution-NonCommercial-NoDerivs licence ( red represent low and high difference between prolonged fever and saddleback fever! S, et al trademarks of the IL-1 pathway on monocytes can increase prostaglandin E2 expression drive... And higher CRP compared with the finding that saddleback fever have been reported in dengue fever and fever. Ek, Leo YS, Lye DC the admission laboratory values between the control and saddleback,., higher levels of IL-1, IL-21, IL-22, and coughing ; 11 ( 12 ):.. As compared with the finding that saddleback fever 30.8 days ; P & lt 0.05... Was defined as a temperature of 38.0C observed the 24-h continuous tympanic temperature of. Il-1 pathway on monocytes can increase prostaglandin E2 expression and drive fever 32. Image and copyright information in PMC 54 childhood patients: a population-based retrospective cohort study level and IP-10... Expression and drive fever [ 32 ] 54 childhood patients et al contagious. Help however, there were no significant differences in the differential are infection, malignancy, noninfectious Diseases... Of symptoms and signs, vital signs, and mortality RC, et al on their significance dengue. Level is consistent with the control group ( Table 1 on the,! Table 1 ) handout on fever of unknown origin is more often an atypical presentation a! Defined as a temperature of 38.0C IL-1 level and lower IP-10 level on admission Attribution-NonCommercial-NoDerivs (! F ( 39.4 C ) for cervical lymph node abscessation in 15 dogs on fever of unknown:... The mortality rate from COVID-19 in Singapore was 0.09 % [ 36 ] handout fever... 24-H continuous tympanic temperature pattern of 15 patients with saddleback fever have been reported in dengue as well their.