However, unlike RA, rheumatic . 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. 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. 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. Clinical and laboratory predictive markers for acute dengue infection. 2021 Jan-Feb;50(1):28-32. doi: 10.1016/j.hrtlng.2020.10.013. 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]. 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 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. See permissionsforcopyrightquestions and/or permission requests. Rowe EK, Leo Y-S, Wong JGX, Thein T-L, Gan VC, Lee LK, et al. Front Cell Infect Microbiol. Clipboard, Search History, and several other advanced features are temporarily unavailable. Am J Dis Child 1972; 124:544. eCollection 2017 Summer. Pizzo PA, Lovejoy FH Jr, Smith DH. Bethesda, MD 20894, Web Policies Statistical analyses were performed using Stata, version 14 (StataCorp, College Station, TX, USA). 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. Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). The fever itself is generally harmless and probably helpful. Based on this study, patients with saddleback fever who remain well can be monitored in the community, while patients who have fever for >7 days should be admitted for closer monitoring., The hospital-based case-control study included 142 patients who were admitted to the NCID with COVID-19. 2013 Oct 20;20(1):75. doi: 10.1186/1423-0127-20-75. 2020 Oct 28;21(1):897. doi: 10.1186/s13063-020-04819-9. [Open Forum Infect Dis 2020;7:ofaa375]. . Disclaimer. J Microbiol Immunol Infect. We also excluded 4 patients whose fever pattern did not fulfill the case definition for prolonged or saddleback fever. Blue and red represent low and high concentrations, respectively. 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. Prolonged fever is associated with adverse outcomes in dengue viral infection. Hypoxia was defined as requirement for supplemental oxygen. Fever often occurs in response to infection, inflammation and trauma. 2013 Jul;23(7):463-7. . Prolonged fever in children: review of 100 cases. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. But there are some important differences. If the diagnosis remains elusive, 18F fluorodeoxyglucose positron emission tomography plus computed tomography may help guide the clinician toward tissue biopsy. Prolonged fever lasting more than 7 days after illness onset can help physicians identify patients at high risk for adverse outcomes from COVID-19, according to a study. Repeat laboratory investigations and CXR were done for those with prolonged or saddleback fever and collected. Would you like email updates of new search results? Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. Bookshelf Search dates: November 28, 2011; February 8, 2012; and April 18, 2014. Corticosteroids for treating mild COVID-19: opening the floodgates of therapeutic misadventure. FOIA 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. An official website of the United States government. Careers. In conclusion, we reported on the prevalence, risk factors, cytokine profiles, and outcomes of patients with COVID-19 who had saddleback or prolonged fever. J Clin Med Res. Despite the progression on CXR in over one-third of cases with saddleback fever, these cases tend to do well. 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. Both prolonged fever and saddleback fever were not significantly associated with mechanical ventilation as compared with the control group (Table 1). COVID-19 generally presents as an acute respiratory illness, with fever, fatigue, and dry cough being commonly reported symptoms [46]. -, Huang C, Wang Y, Li X, et al. Some children also may have a sore throat, runny nose or cough along with or before the fever. Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel. This corresponded with a rise in CRP and LDH seen in cases with prolonged fever, which are known to be associated with adverse prognostic factors in COVID-19 [15, 16]. Fever was defined as a temperature of 38.0C. Never give a child aspirin, as this increases the risk of . Those with prolonged fever had a median duration of fever (interquartile range [IQR]) of 10 (9-11) days for prolonged fever cases, while fever recurred at a median (IQR) of 10 (8-12) days for those with saddleback fever. as they fulfilled overlapping criteria for prolonged and saddleback fever. Blue and red represent low and high concentrations, respectively. Epub 2022 Aug 27. 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. People who wish to treat a fever can try over-the-counter anti-fever medications, such as acetaminophen, aspirin, or ibuprofen. 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. Patients with saddleback fever appeared to have good outcomes regardless of the fever, they noted. The 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern of haemorrhagic complications. In patients with saddleback fever, higher levels of IL-1, IL-21, IL-22, and SDF-1 were observed compared with control patients. Europe PMC is an archive of life sciences journal literature. A larger sample size may help to identify if prolonged and saddleback fever could be used as predictors for adverse outcomes such as ICU admission, mechanical ventilation, or death. 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). This site needs JavaScript to work properly. 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. Available at: Wang D, Hu B, Hu C, et al. The 18F fluorodeoxyglucose has better uptake and is cleared more rapidly than older modalities (e.g., gallium Ga 67 citrate), but it is costly and not widely available.14, Liver, lymph node, or temporal artery biopsy may help establish a definitive diagnosis.3,19 A prospective study of 192 patients found that biopsies produced up to a 35% diagnostic yield (about 10% to 35%), especially if performed later in the evaluation when infection is less likely, and malignancies and noninfectious inflammatory diseases are more common.2 Liver biopsy, with a diagnostic yield between 14% and 17%,5,19 can reveal granulomatous hepatitis and determine its cause, which could be infectious, inflammatory, or neoplastic processes.22,27 Lymph node biopsy is most useful in diagnosing lymphoma, infectious diseases, and granulomatous diseases.19,27 In patients 55 years or older, temporal arteritis causes more than 15% of cases of FUO, so biopsy should be considered.5,15,18, Bone marrow biopsy is diagnostically useful, particularly with neoplasm and infectious disease, especially tuberculosis.19,27 One study of 280 hospitalized febrile patients found that bone marrow biopsy was helpful in reaching a diagnosis in nearly 25% of the 130 patients who underwent biopsy.41 Conversely, bone marrow aspiration and culture have a diagnostic yield of only 0% to 2%.3,5,15,22,41. is funded by the National Medical Research Council (NMRC/Fellowship/0056/2018). The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. Emadi A, Chua JV, Talwani R, Bentzen SM, Baddley J. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. 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. Methods: The global distribution and burden of dengue. 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). 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. COVID-19 and sinus infections share several symptoms like nasal congestion, fever, and coughing. Your comment will be reviewed and published at the journal's discretion. There were no deaths in our study. 2014; 8: e2777 10.1371/journal.pntd.0002777 Infect Drug Resist. 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]. Based on this study, patients with saddleback fever who remain well can be monitored in the community, while patients who have fever for >7 days should be admitted for closer monitoring. Antibiotics usually aren't prescribed just because a child has a fever that is lasting a long time. Murthy S, Archambault PM, Atique A, Carrier FM, Cheng MP, Codan C, Daneman N, Dechert W, Douglas S, Fiest KM, Fowler R, Goco G, Gu Y, Guerguerian AM, Hall R, Hsu JM, Joffe A, Jouvet P, Kelly L, Kho ME, Kruisselbrink RJ, Kumar D, Kutsogiannis DJ, Lamontagne F, Lee TC, Menon K, O'Grady H, O'Hearn K, Ovakim DH, Pharand SG, Pitre T, Reel R, Reeve B, Rewa O, Richardson D, Rishu A, Sandhu G, Sarfo-Mensah S, Shadowitz E, Sligl W, Solomon J, Stelfox HT, Swanson A, Tessier-Grenier H, Tsang JLY, Wood G; SPRINT-SARI Canada Investigators and the Canadian Critical Care Trials Group. Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. However, there were no significant differences in the admission laboratory values between the control and saddleback fever groups. Patients with prolonged fever may have had higher levels of IL-1 earlier on before sample collection. . Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 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. A, Heatmap showing the relative concentration of cytokines across patients with different fever patterns. However, it is interesting that there are higher pro-inflammatory IL-1 levels in patients with saddleback fever. Lohr JA, Hendley JO. Nevertheless, as patients in the ICU are at higher risk of nosocomial infections, due diligence should be done to exclude other causes of fever [17]. The https:// ensures that you are connecting to the Duration of fever was prolonged with increased age. 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. sharing sensitive information, make sure youre on a federal This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. 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. Your child may also develop swollen lymph nodes in the neck. 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. 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). 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. -. Laboratory Results for Prolonged and Saddleback Fever. Rheumatic fever mostly affects children aged 5-15 years, but it is rare in adults and children aged under 3 years. Before 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]. The average body temperature is 98.6 F (37 C). 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. eCollection 2022. The definition of what constitutes FUO remains controversial.1,2 FUO was first described in a 1961 case series as prolonged febrile illness (temperature of 101F [38.3C] or higher) for three weeks or longer that did not have an established etiology despite a one-week inpatient evaluation.3,4 The arbitrarily defined three weeks allowed most acute, self-limited illnesses to resolve, as well as sufficient time to complete the initial investigation.5,6, FUO was further defined in 1991, suggesting that the minimum evaluation be changed to at least three outpatient visits or three days in inpatient care.7 Others have proposed shorter lengths of time (e.g., two weeks, because today's patients present earlier and receive a diagnosis more quickly).8,9 A retrospective review of 226 hospitalized febrile patients examined the timing of diagnosis from initial visit for fever through the end of hospitalization. Search life-sciences literature (41,164,937 (41,164,937 Empiric trials of antibiotics or steroids rarely establish a diagnosis and are discouraged in the management of patients with FUO, unless there are clinical indications.5,17,19,21,22 Consultation with a subspecialist (e.g., infectious disease specialist, rheumatologist, hematologist/oncologist) is appropriate at any point in the evaluation. Please enable it to take advantage of the complete set of features! A fever is a rise in body temperature. 8600 Rockville Pike Over- or under-reporting of the onset of fever before admission could affect the number of patients found to have prolonged or saddleback fever. In contrast, cases with saddleback fever showed no significant change upon repeating their laboratory tests. Hirata K, Watanabe K, Sasaki T, Yoshimasu T, Shimomura A, Ando N, Yanagawa Y, Mizushima D, Teruya K, Kikuchi Y, Oka S, Tsukada K. Oxf Med Case Reports. 40-year-old woman fever rash arthralgia Dx? Coronavirus disease 2019 (COVID-19) situation report101.2020. Recommendations of the Scientific Working Group on Dengue. Oxford University Press is a department of the University of Oxford. eCollection 2022. 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). Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever. Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. 2016 Dec 9;11(12):e0167025. 2022 Oct 31;12:1009894. doi: 10.3389/fcimb.2022.1009894. 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. Institutional research board ethics approval and written consent were obtained for the drawing of blood specimens from participants for cytokine analysis (ref: DRSB 2012/00917). Roseola often starts with a high fever often higher than 103 F (39.4 C). 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. While both prolonged and saddleback fever showed an association with hypoxia, only prolonged fever was associated with ICU admission. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. This site needs JavaScript to work properly. eCollection 2016. 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]. amendys-Silva SA, Alvarado-vila PE, Domnguez-Cherit G, Rivero-Sigarroa E, Snchez-Hurtado LA, Gutirrez-Villaseor A, Romero-Gonzlez JP, Rodrguez-Bautista H, Garca-Briones A, Garnica-Camacho CE, Cruz-Ruiz NG, Gonzlez-Herrera MO, Garca-Guilln FJ, Guerrero-Gutirrez MA, Salmern-Gonzlez JD, Romero-Gutirrez L, Canto-Castro JL, Cervantes VH; Mexico COVID-19 Critical Care Collaborative Group. Respiratory illness, with fever, fatigue, and SDF-1 were observed compared the! Emission tomography plus computed tomography may help guide the clinician toward tissue.. 8: e2777 10.1371/journal.pntd.0002777 Infect Drug Resist and several other advanced features are unavailable. 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