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. 2016 Dec 9;11(12):e0167025. These patients required prolonged periods of observation and symptomatic treatment. Available at: Ministry of Health (MOH) Singapore. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. Fever was defined as a temperature of 38.0C. The presence of prolonged or saddleback fever in dengue patients should therefore prompt detailed evaluation for complications of dengue, as well as early investigation to evaluate for development of nosocomial infection. . 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
In many cases, no specific cause of the fever is found, 2 . Interestingly, there are also higher plasma levels of IL-1RA in patients with prolonged fever compared with control patients. Statistical data analysis on the types of fevers The .gov means its official. Patients who tested positive were not discharged until they had 2 negative PCR tests 24 hours apart [13]. 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. 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. 2013 Jul;23(7):463-7. Patients with saddleback fever appeared to have good outcomes regardless of the fever, they noted. Infections predominate early in FUO diagnoses, and the longer FUO remains undiagnosed, the less likely it is caused by an infection.27 After infections, the etiology of FUO transitions to noninfectious inflammatory diseases and malignancies, which can guide subsequent testing. The author(s) received no specific funding for this work. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. 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. 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 ). Fever was defined as a temperature of 38.0C. Fever, face edema, fatigue, fungal infection, malaise, . Prevalence and Predictors of Persistent Symptoms After Clearance of SARS-CoV-2 Infection: A Multicenter Study from Egypt. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). COVID-19 and sinus infections share several symptoms like nasal congestion, fever, and coughing. Oxford University Press is a department of the University of Oxford. Retrospective characterisation and outcome of surgical treatment for cervical lymph node abscessation in 15 dogs. Duration of fever was calculated from the date of first symptom onset to the date of defervescence (defined as temperature <37.5C for at least 24 hours) during the hospital admission. Bookshelf Copyright 2023 American Academy of Family Physicians. Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. There were no deaths in our study. 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. CONCLUSIONS: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. 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. Age-appropriate or potentially diagnostic clueguided cancer screening should be performed (e.g., colonoscopy in patients 50 years or older). The mean duration of symptoms and signs before diagnosis (28.4 13.2 versus 45.0 30.8 days; P < 0.05), . 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. 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]. 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. 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). For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Cases with prolonged fever were found to have higher levels of anti-inflammatory IL-1RA, pro-inflammatory IL-6, and chemokine interferon- IP-10 compared with controls (Figure 1B). A more recent qualitative definition requires only a reasonable diagnostic evaluation. 2016 May 20;10(5):e0004575. Trials. In general, fever is defined as a temperature > 38C (100.4F). 2022 Oct 31;12:1009894. doi: 10.3389/fcimb.2022.1009894. Infect Drug Resist. Although there are more than 200 diseases in the differential diagnosis, most cases in adults are limited to several dozen possible causes. Cytokine level for healthy controls (n=23) is indicated by the black dotted line. Importantly, upregulation of the IL-1 pathway on monocytes can increase prostaglandin E2 expression and drive fever [32]. sharing sensitive information, make sure youre on a federal Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). doi: 10.1093/ofid/ofx133. 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). A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. Europe PMC is an archive of life sciences journal literature. Additional references were identified from the articles reviewed. Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. 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]. Statistical analyses were performed with the Mann-Whitney U test (*P<.05; **P<.01; ***P<.001). A. To investigate whether the fever patterns experienced by the patients are due to differences in immune responses, concentrations of 45 immune mediators were profiled. This site needs JavaScript to work properly. For cytokine profiling, the Mann-Whitney U test was applied to ascertain significant differences in immune mediator levels between patients experiencing different fever patterns. official website and that any information you provide is encrypted 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). Such facilities free up hospital beds to enable sicker patients to be optimally managed. This can happen when your body is fighting an infection. 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. The classic presentation is one of fever, malaise, diffuse abdominal pain, and constipation. 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. In conclusion, we reported on the prevalence, risk factors, cytokine profiles, and outcomes of patients with COVID-19 who had saddleback or prolonged fever. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. 2014; 8: e2777 10.1371/journal.pntd.0002777 More studies are required to validate the findings of this report. COVID-19 generally presents as an acute respiratory illness, with fever, fatigue, and dry cough being commonly reported symptoms [46]. Repeat CXR was not performed for cases in the control group and 1 case of saddleback fever. 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. A P value of<.05 indicated statistical significance. Fever is a nonspecific symptom that may be caused by infectious and noninfectious conditions, including malignancies, systemic rheumatic diseases, and drug reactions. Approval for data collection by retrospective chart review with a waiver of written informed consent from study participants was granted by the Singapore Ministry of Health under the Infectious Diseases Act as part of the outbreak investigation [14]. 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. 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. In addition, IP-10 has also been reported to be associated with increased viral load, lung injury, ICU admission, and mortality [21]. ; Singapore 2019 Novel Coronavirus Outbreak Research Team. No overall differences in safety or effectiveness . Seven more confirmed cases of novel coronavirus infection in Singapore. Potential conflicts of interest. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Woon YL, Hor CP, Hussin N, Zakaria A, Goh PP, Cheah WK. RSV is a contagious illness that infects the respiratory tract and can lead to more severe infections like pneumonia or bronchiolitis. Prolonged fever was defined as fever lasting more than 7 days. Europe PMC is an archive of life sciences journal literature. Clinical and laboratory predictive markers for acute dengue infection. The Author(s) 2020. All authors: no reported conflicts of interest. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (. We also excluded 4 patients whose fever pattern did not fulfill the case definition for prolonged or saddleback fever. When there are no clear localizing signs or symptoms, clinicians should expand on the patient's symptoms and historical information, looking for potentially diagnostic clues to guide the evaluation (Table 4).1720,25,27 This is a continuous, iterative process.1921 Potentially diagnostic clues lead to a diagnosis in 62% of patients, although clues can be misleading because they are found in 97% of patients.1517, If no potentially diagnostic clues are found, a minimum diagnostic workup should be performed. 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 . 2022 May 20;15:2575-2587. doi: 10.2147/IDR.S355064. Fever was defined as a temperature of 38.0C. "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. Never give a child aspirin, as this increases the risk of . Thank you for submitting a comment on this article. Higher respiratory rate, lower SpO2, and lower systolic BP were also associated with saddleback fever compared with the control group. 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). 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. CMAJ Open. doi: 10.1371/journal.pntd.0004575. 2022 Jul 26;2022(7):omac079. The variance between the highest and lowest core temperature in a given day is usually no more than 1 to 1.5C. 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. 2022 Dec;55(6 Pt 1):1044-1051. doi: 10.1016/j.jmii.2022.07.009. 2020 Oct 1;180(10):1345-1355. doi: 10.1001/jamainternmed.2020.3539. A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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]. 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. Fever duration was longer in patients 6 to 12 months old and 12 to 18 . 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. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures.2020. Pizzo PA, Lovejoy FH Jr, Smith DH. PLoS Negl Trop Dis. 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). There was no difference in types of diagnoses for those who met the strict 1991 definition compared with those who received a diagnosis in less than three weeks.10 Therefore, FUO may be assumed when no reasonable diagnosis is reached after an appropriate inpatient or outpatient investigation.2,6,1017 Table 1 compares the evolution of the definition of FUO.2,3,6,7,1017, Other subtypes of FUO are nosocomial, neutropenic, and human immunodeficiency virusassociated.7 These subtypes have different approaches to evaluation and are beyond the scope of this article.17, The etiologies of FUO have changed over time because of shifting disease patterns and new diagnostic techniques.14 There are more than 200 diseases in the differential diagnosis.4,15,17 In multiple case series, however, the etiology of FUO is limited to several dozen causes, and patients often have an atypical presentation of a common disease.2,6,18. Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). doi: 10.1371/journal.pone.0167025. The site is secure. For most people, a temperature of 98.6 F or 37 C is baseline. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P=.05). Financial support. Ng DH, Wong JG, Thein TL, Leo YS, Lye DC. Infection, malaise, diffuse abdominal pain, and several other advanced features are temporarily.. Increases the risk of adverse outcomes from COVID-19 collected during the acute phase ( median onset. Did not fulfill the case definition for prolonged or saddleback fever cases the... Duration of symptoms and signs before diagnosis ( 28.4 13.2 versus 45.0 30.8 days ; P & lt ; ). Versus 45.0 30.8 days ; P & lt ; 0.05 ), for... Hhs ) defined as fever lasting more than 200 diseases in the diagnosis. 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difference between prolonged fever and saddleback fever