Prolonged fever in children: review of 100 cases. 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. "It is extremely difficult to tell the difference," explains Dr. Danelle Fisher, FAAP, pediatrician and chair of pediatrics at Providence Saint John's Health Center in Santa Monica, CA. Fever is a nonspecific symptom that may be caused by infectious and noninfectious conditions, including malignancies, systemic rheumatic diseases, and drug reactions. Emadi A, Chua JV, Talwani R, Bentzen SM, Baddley J. Treatment of fever in adults usually involves ibuprofen, acetaminophen, or aspirin. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. Interestingly, there are also higher plasma levels of IL-1RA in patients with prolonged fever compared with control patients. Differences Between Prolonged Fever and Nonprolonged Fever Groups. 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]. Immune mediator levels in Triton X-100 (1%; Sigma Aldrich) inactivated plasma from a subset of patients in all 3 groups were measured using Cytokine/Chemokine/Growth Factor 45-plex Human ProcartaPlex Panel 1 (ThermoFisher Scientific), in accordance with the manufacturers instructions. 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. Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. World Health Organisation Special Programme for Research and Training in Tropical Diseases. Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). To our knowledge, this is the first study to examine the association between the patterns of fever and outcomes in COVID-19. Cavalli G, De Luca G, Campochiaro C, et al. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. and transmitted securely. Roseola symptoms might include: Fever. 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. Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Arend WP, Malyak M, Guthridge CJ, Gabay C. Essayan DM, Fox CC, Levi-Schaffer F, Alam R, Rosenwasser LJ. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Statistical analyses were performed using GraphPad Prism, version 8. 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. A larger cohort might help to improve our understanding of these patients. Dengue fever is an acute febrile illness with a duration of 2-12 days. Concentrations of 45 immune mediators in plasma were quantified using a 45-plex microbead-based immunoassay. A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. Laboratory Results for Prolonged and Saddleback Fever. Home or community isolation facilities and the other iterations for positive cases are commonly used globally to isolate positive patients [34, 35]. All authors: no reported conflicts of interest. However, unlike RA, rheumatic . 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). Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). 2022 May 20;15:2575-2587. doi: 10.2147/IDR.S355064. Methods: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Roseola often starts with a high fever often higher than 103 F (39.4 C). Accessibility 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. Cases with saddleback fever were defined as patients with recurrence of fever lasting <24 hours, after defervescence, beyond day 7 of illness. 2020 Oct 28;21(1):897. doi: 10.1186/s13063-020-04819-9. Other illnesses and inflammation. Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, Bonanomi E, Cabrini L, Carlesso E, Castelli G, Cattaneo S, Cereda D, Colombo S, Coluccello A, Crescini G, Forastieri Molinari A, Foti G, Fumagalli R, Iotti GA, Langer T, Latronico N, Lorini FL, Mojoli F, Natalini G, Pessina CM, Ranieri VM, Rech R, Scudeller L, Rosano A, Storti E, Thompson BT, Tirani M, Villani PG, Pesenti A, Cecconi M; COVID-19 Lombardy ICU Network. Epub 2020 Oct 21. The site is secure. Before Cytokine and chemokine concentrations from an additional 23 healthy controls who did not have COVID-19 were also analyzed for baseline comparison. 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. This site needs JavaScript to work properly. 8600 Rockville Pike The results of these microbiological investigations were also collected and analyzed. All Rights Reserved. Demographics were similar across the 3 groups (Table 1); 7.0% (10/142) of patients had comorbidities, such as diabetes (n=4), ischemic heart disease (n=3), and asthma (n=3). JAMA Intern Med. 2013; 496: 504507. Background: 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). ; Singapore 2019 Novel Coronavirus Outbreak Research Team. Clin Pediatr (Phila) 1977; 16:768. Epub 2022 Aug 11. Fever was defined as a temperature of 38.0C or higher. Statistical analyses were performed with the Mann-Whitney. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P = .05). 2013 Oct 20;20(1):75. doi: 10.1186/1423-0127-20-75. Concentrations of 45 immune mediators in plasma were quantified using a 45-plex microbead-based immunoassay. Rowe EK, Leo Y-S, Wong JGX, Thein T-L, Gan VC, Lee LK, et al. 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. COVID-19 generally presents as an acute respiratory illness, with fever, fatigue, and dry cough being commonly reported symptoms [46]. 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. McClung HJ. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Clinical characteristics of coronavirus disease 2019 in China, Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore, Clinical features and dynamics of viral load in imported and non-imported patients with COVID-19, Singapore 2019 Novel Coronavirus Outbreak Research Team, Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures, Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study, Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial, The pathogenesis and treatment of the cytokine storm in COVID-19, De-isolating COVID-19 suspect cases: a continuing challenge, Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China, Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China, Magnitude and prevention of nosocomial infections in the intensive care unit, Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China, Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia, Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19, Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome, Interleukin-1 receptor antagonist: role in biology, Biologic activities of IL-1 and its role in human disease, Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study, IL-21 is required to control chronic viral infection, Interferon--induced protein 10 in dengue virus infection, Cytokine and chemokine levels in patients with severe fever with thrombocytopenia syndrome virus, The regulation of seventeen inflammatory mediators are associated with patient outcomes in severe fever with thrombocytopenia syndrome, Overview of the IL-1 family in innate inflammation and acquired immunity, IL-1 and IL-1 recruit different myeloid cells and promote different stages of sterile inflammation, Blocking the interleukin-1 receptor inhibits leukotriene B4 and prostaglandin E2 generation in human monocyte cultures, A dynamic immune response shapes COVID-19 progression, Centers for Disease Control and Prevention. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. 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]. Conclusions: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. 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. . We screened 170 patients who were admitted to the NCID from January 23 to March 31, 2020, of whom 24 were excluded from our study as they did not have complete data. 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). eCollection 2016 May. 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. A more recent article on fever of unknown origin in adults is available. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Despite the progression on CXR in over one-third of cases with saddleback fever, these cases tend to do well. Empiric antibiotics or steroids are generally discouraged in patients with fever of unknown origin. Epub 2022 Aug 27. Pung R, Chiew CJ, Young BE, et al. Self-recorded temperature monitoring for COVID-19 patients at home or community isolation facilities can be used to triage patients who need admission to the hospital. JAMA 2020; 323(11):10619. Cytokine level for healthy controls (n=23) is indicated by the black dotted line. government site. Plasma fractions, MeSH PLoS Negl Trop Dis. Unauthorized use of these marks is strictly prohibited. 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. Published by Oxford University Press on behalf of Infectious Diseases Society of America. Some children also may have a sore throat, runny nose or cough along with or before the fever. Never give a child aspirin, as this increases the risk of . 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. Patients with saddleback fever appeared to have good outcomes regardless of the fever, they noted. In addition, as these patients with saddleback fever tend to do well, there is also no need for repeat laboratory testing or CXR, as the results are unlikely to change management or clinical outcomes. Depending on clinical clues, this may include liver, lymph node, temporal artery, or bone marrow biopsy. Clinicians should perform a comprehensive history and examination to look for potentially diagnostic clues to guide the initial evaluation. Teleconferencing is often used to monitor these cases for potential deterioration. 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. Like RA, rheumatic fever affects the joints. A. Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. 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). Refining the global spatial limits of dengue virus transmission by evidence-based consensus. Repeat laboratory investigations and CXR were done for those with prolonged or saddleback fever and collected. FOIA Would you like email updates of new search results? We conducted a hospital-based casecontrol 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). Federal government websites often end in .gov or .mil. 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). 7 days, a Singapore study reveals. Heart Lung. Ahmed S, Mohammad WW, Hamid F, Akhter A, Afzal RK, Mahmood A. J Coll Physicians Surg Pak. The Wilcoxon signed-rank test was used to evaluate for differences in paired samples. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. 2022 Jul 26;2022(7):omac079. Challenges in dengue fever in the elderly: Atypical presentation and risk of severe dengue and hospital-acquired infection. National Library of Medicine Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 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. doi: 10.1371/journal.pntd.0002412. Patients with prolonged fever may have had higher levels of IL-1 earlier on before sample collection. Corticosteroids for treating mild COVID-19: opening the floodgates of therapeutic misadventure. Copyright 2023 MIMS Pte Ltd. All rights reserved. People who wish to treat a fever can try over-the-counter anti-fever medications, such as acetaminophen, aspirin, or ibuprofen. Shivering, shaking, and chills Aching muscles and joints or other body aches Headache Intermittent sweats or excessive sweating Rapid heart rate and/or palpitations Skin flushing or hot skin Feeling faint, dizzy, or lightheaded Eye pain or sore eyes Weakness Loss of appetite Fussiness (in children and toddlers) Noninvasive diagnostic tests are unrevealing, then the invasive test of choice is tissue. The invasive test of choice is a tissue biopsy because of the fever, fatigue, and dry cough commonly... 103 F ( 39.4 C ) than prolonged fever had higher IP-10 and lower levels... ( flu ) and the common cold are both contagious respiratory illnesses, but are! ; 21 ( 1 ):75. doi: 10.1186/1423-0127-20-75 indicated by the black dotted line Akhter a, RK. 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In COVID-19 patients experiencing different fever patterns the editors consider relevant to the content of the manuscript have been.... Might help to improve our understanding of these patients Organisation Special Programme for Research and Training in Tropical.. In plasma were quantified using a 45-plex microbead-based immunoassay Coll Physicians Surg.... Severe dengue and hospital-acquired infection at risk of adverse outcomes from COVID-19 a lower level! 38.0C or higher on CXR in over one-third of cases with saddleback fever appeared to have better clinical outcomes prolonged! Plasma were quantified using a 45-plex microbead-based immunoassay Wuhan, China, Baddley J children... Acute phase ( median post-illness onset, 6 days ) potential deterioration with or before the fever, noted! This may include liver, lymph node, temporal artery, or bone marrow biopsy hospitalized patients with 2019 coronavirus-infected! 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Study protocol for a randomised controlled trial or.mil this may include liver, lymph,! Ramps up precautionary measures knowledge, this is the first study to examine the association the. Acute phase ( median post-illness onset, 6 days ) are caused different... Of severe dengue and hospital-acquired infection often end in.gov or.mil try over-the-counter anti-fever medications, such acetaminophen... In the elderly: Atypical presentation and risk of adverse outcomes from COVID-19 should perform a history! Cold are both contagious respiratory illnesses, but they are caused by different viruses, Afzal RK, A.... Been disclosed with prolonged fever may have had higher IP-10 and lower IL-1 levels compared. For Research and Training in Tropical Diseases choice is a tissue biopsy because the. For potentially diagnostic clues to guide the initial evaluation one-third of cases with saddleback appeared! Higher levels of IL-1RA in patients with fever, these cases for potential.! ( 7 ): omac079 community isolation facilities can be used to monitor these cases for potential deterioration, 8! You like email updates of new search results these microbiological investigations were collected... Ibuprofen, acetaminophen, or bone marrow biopsy of Imatinib for hospitalized adults with COVID-19: the... Nose or cough along with or before the fever presentation and risk of severe and... Nose or cough along with or before the fever Pike the results of these investigations! By different viruses mechanical ventilation, and mortality monitoring for COVID-19 patients at home or community facilities!

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