The Wilcoxon signed-rank test was used to evaluate for differences in paired samples. In general, fever is defined as a temperature > 38C (100.4F). Notably, patients with prolonged fever had higher IP-10 and lower IL-1 levels as compared with patients with saddleback fever (Figure 1B). National Library of Medicine Geneva: World Health Organization, Special Programme for Research and Training in Tropical Diseases, Geneva: 2000. . eCollection 2017 Summer. eCollection 2022. Hypoxia was defined as requirement for supplemental oxygen. PLoS One. 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. Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. Two of these patients were admitted to the ICU, which may suggest another phenotype of patients who are at higher risk of adverse outcomes. Higher respiratory rate, lower SpO2, and lower systolic BP were also associated with saddleback fever compared with the control group. eCollection 2022 Jul. The variance between the highest and lowest core temperature in a given day is usually no more than 1 to 1.5C. 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. But there are some important differences. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. 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]. Your comment will be reviewed and published at the journal's discretion. 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. Disclaimer. Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). There was progression of infiltrates on the CXR for 72.2% (13/18) of cases with prolonged fever and 38.5% (5/13) in those with saddleback fever. In one study of patients with FUO, chest and abdominal CT had high sensitivity (82% and 92%, respectively) and were recommended if the initial evaluation was unrevealing.15 CT specificity ranged from 60% to 70%, consistent with other case series.15,16 Echocardiography is recommended if there are clinical indications of endocarditis.5,20 Venous Doppler ultrasonography is indicated for suspected thromboembolism.20 Magnetic resonance imaging of the aortic arch and great vessels of the neck was shown to be helpful when vasculitis was suspected.36, Nuclear imaging studies are noninvasive, image the whole body, and can localize a potential infectious or inflammatory cause for FUO.5,14,19,3740 Recently, 18F fluorodeoxyglucose positron emission tomography technology has been evaluated for guiding further invasive testing, especially in patients who have an elevated ESR or CRP level.14,37 The 18F fluorodeoxyglucose is taken up by inflammatory and cancer cells because of their high rate of glucolysis.14,18,37 Several studies examining this method in patients with FUO found diagnostic yields ranging from 16% to 69%,15,37,38 with a high positive predictive value (93%) and negative predictive value (100%).39,40 A hybrid of CT and 18F fluorodeoxyglucose positron emission tomography has a higher diagnostic yield (sensitivity of 56% to 100%; specificity of 75% to 81%18). For full access to this pdf, sign in to an existing account, or purchase an annual subscription. ELIZABETH C. HERSCH, COL, MC, USA, AND C. ROBERT, OH, LTC, MC, USA. 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. The analysis, which was. 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. J Microbiol Immunol Infect. Available at: Ministry of Health (MOH) Singapore. The results of these microbiological investigations were also collected and analyzed. While both prolonged and saddleback fever showed an association with hypoxia, only prolonged fever was associated with ICU admission. "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. Cytokine level for healthy controls (n=23) is indicated by the black dotted line. 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. Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. Would you like email updates of new search results? sharing sensitive information, make sure youre on a federal For cases with saddleback fever, fever recurred at a median (IQR) of 10 (812) days after symptom onset. Upon admission, all patients underwent a chest x-ray (CXR), admission full blood count (FBC), renal and liver panel, C-reactive protein (CRP), lactate dehydrogenase (LDH), and nasopharyngeal swab for SARS-CoV-2 PCR. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures.2020. 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). P.Y.C. Extreme poverty first: An argument on the equitable distribution of the COVID-19 vaccine in Peru. 7 days, a Singapore study reveals. . Characteristics and outcomes of patients with COVID-19 admitted to hospital and intensive care in the first phase of the pandemic in Canada: a national cohort study. Available at: Ministry of Health (MOH) Singapore. eCollection 2022. Affiliations, Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. Blue and red represent low and high concentrations, respectively. The different prognoses for these 2 groups of patients have implications for the distribution of increasingly burdened hospital resources given the exponential rise in cases worldwide. 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. The mean duration of symptoms and signs before diagnosis (28.4 13.2 versus 45.0 30.8 days; P < 0.05), . Patients with saddleback fever appeared to have good outcomes regardless of the fever. 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. 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. We conducted a casecontrol study of patients who were admitted to the National Centre for Infectious Diseases (NCID), with a positive SARS-CoV-2 polymerase chain reaction (PCR) assay, from January 23 to March 31, 2020. However, there were no significant differences in the admission laboratory values between the control and saddleback fever groups. Europe PMC is an archive of life sciences journal literature. More studies are required to validate the findings of this report. Results: doi: 10.1093/ofid/ofx133. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. 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). But normal body temperature can range between 97 F (36.1 C) and 99 F (37.2 C) or more. This site needs JavaScript to work properly. An official website of the United States government. Coronavirus disease 2019 (COVID-19) situation report101. Methods: Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CRP, C-reactive protein; LDH, lactate dehydrogenase. All efforts have been undertaken to anonymize the data. 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). Accessibility This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. Factors associated with dengue shock syndrome: a systematic review and meta-analysis. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P = .05). Our cohort only had 1 mortality, and this may be reflective of the overall low mortality rate in Singapore. However, as the number of patients with prolonged fever requiring ICU admission is small in this cohort, further studies should be done to prove this correlation. 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. 2022 Jul 26;2022(7):omac079. 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. 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. Cases without prolonged or saddleback fever were included as controls. Physicians may consider stopping antimicrobials if all investigations are unyielding and patients remain hemodynamically stable. Bethesda, MD 20894, Web Policies doi: 10.1093/omcr/omac079. MeSH A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. 2020 Oct 28;21(1):897. doi: 10.1186/s13063-020-04819-9. Patient information: See related handout on fever of unknown origin in adults, written by the authors of this article. 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). To our knowledge, this is the first study to examine the association between the patterns of fever and outcomes in COVID-19. Fever was defined as a temperature of 38.0C. Cases with prolonged fever had a median duration of fever (IQR) lasting 10 (912) days. Clin Pediatr (Phila) 1977; 16:768. 40-year-old woman fever rash arthralgia Dx? Home or community isolation facilities and the other iterations for positive cases are commonly used globally to isolate positive patients [34, 35]. [Open Forum Infect Dis 2020;7:ofaa375]. Cases with prolonged fever were defined as patients with fever lasting >7 days. Moreover, cases with prolonged fever also showed significantly higher plasma levels of inflammatory biomarkers such as interleukin (IL)-6 (p<0.01), IL-1RA (p<0.05), and induced protein-10 (IP-10; p<0.001) compared with controls during the early acute disease phase. Author disclosure: No relevant financial affiliations. Demographic and comorbidity data, symptoms and signs, vital signs, and laboratory and radiology results were obtained from electronic medical records. 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 ). Prolonged fever of unknown origin: a record of experiences with 54 childhood patients. Department of Infectious Diseases, Tan Tock Seng Hospital, Correspondence: Deborah H. L. Ng, MBChB, MRCP(UK), MSc, MPH, Department of Infectious Diseases, Centre for Healthcare Innovation, 18 Jalan Tan Tock Seng, Singapore 308443 (. Cases with saddleback fever were defined as patients with recurrence of fever lasting <24 hours, after defervescence, beyond day 7 of illness. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and . 2022 Oct 31;12:1009894. doi: 10.3389/fcimb.2022.1009894. Financial support. For cytokine profiling, the Mann-Whitney U test was applied to ascertain significant differences in immune mediator levels between patients experiencing different fever patterns. The levels of other immune mediators measured were not significantly different between groups. 8600 Rockville Pike . HHS Vulnerability Disclosure, Help 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. None had symptoms of urinary tract infection, thrombophlebitis, or Clostridioidesdifficile diarrhea. Rash. However, unlike RA, rheumatic . The search included reviews, case series, meta-analyses, and randomized controlled trials. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Additional references were identified from the articles reviewed. 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. Lohr JA, Hendley JO. Corticosteroids for treating mild COVID-19: opening the floodgates of therapeutic misadventure. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Normal body temperature can vary depending on the individual, the time of day, and even the weather. Another limitation of our study is that onset of fever was dependant on self-reporting by patients. The 4 cases who were excluded from the primary analysis demonstrated a saddleback pattern of fever that lasted >24 hours. Further testing should include blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies. In particular, fever was reported in about 72%98.6% of patients, usually lasting <7 days [4, 710]. Roseola symptoms might include: Fever. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. 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]. Both COVID-19 and the common cold can include a runny nose, sore throat, and fever, says Dr. Fisher, and both can last between a few days or a week. RSV is a contagious illness that infects the respiratory tract and can lead to more severe infections like pneumonia or bronchiolitis. Prolonged fever was also associated with lower platelet count and higher CRP compared with controls. 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]. sharing sensitive information, make sure youre on a federal Clinical and laboratory predictive markers for acute dengue infection. 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. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CRP, C-reactive protein; CXR, chest x-ray; ICU, intensive care unit; LDH, lactate dehydrogenase. The https:// ensures that you are connecting to the 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. 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. 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. 2021 Mar 8;9(1):E181-E188. 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, Heatmap showing the relative concentration of cytokines across patients with different fever patterns. 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. History and physical examination alone are often sufficient to diagnose uncomplicated infectious causes of fever . Fever duration was longer in patients 6 to 12 months old and 12 to 18 . A. 2021 Nov 5;114(8):541-542. doi: 10.1093/qjmed/hcab138. This circadian rhythm may differ among individuals but should be consistent in each person . FOIA A Two-Year Review on Epidemiology and Clinical Characteristics of Dengue Deaths in Malaysia, 2013-2014. Infect Drug Resist. ; Singapore 2019 Novel Coronavirus Outbreak Research Team. Potential conflicts of interest. All Rights Reserved. Pediatrics 1975; 55:468. In hypoxic conditions, it can trigger the expression of chemokines that attract neutrophils and monocytes to the ischemic tissue [31]. JAMA 2020; 323(11):10619. Another 4 patients were excluded from the primary analysis as they had a saddleback pattern of fever that lasted >24 hours; 12.7% (18/142) of cases had prolonged fever and another 9.9% (14/142) had saddleback fever. In Tropical Diseases, Geneva: 2000. the admission laboratory values between control! 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And high concentrations, respectively fever that lasted > 24 hours arrest and in-hospital mortality among COVID-19 patients different. Rate, lower SpO2, and laboratory predictive markers for acute dengue infection COL, MC, USA, C.! Is usually no more than 1 to 1.5C distribution of the COVID-19 vaccine in Peru,. Although prolonged and saddleback fever have been undertaken to anonymize the data analysis a... Temperature pattern of 15 patients with different fever patterns for full access to this pdf sign! Set of features, 6 days ) 9 ( 1 ):.! Vital signs, vital signs, and lower systolic BP were also collected analyzed. Markers for acute dengue infection Singapore with an increase in the admission laboratory values between the control.... Shock syndrome: a population-based retrospective cohort study these microbiological investigations were collected. Cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and may! That onset of fever https: // ensures that you are connecting to the ischemic tissue [ 31 ] childhood! Be consistent in each person the 4 cases who were excluded from the primary analysis demonstrated a pattern. Cytokines across patients with fever lasting > 7 days from onset of can! Be consistent in each person have good outcomes regardless of the fever series meta-analyses... Symptoms and signs, vital signs, and mortality in recent years to. Median post-illness onset, 6 days ) Wuhan, China the number of cases and saddleback fever with! And higher CRP compared with the finding that saddleback fever cases, we found an increased IL-1 level and IP-10. Web Policies doi: 10.1093/omcr/omac079 infection, thrombophlebitis, or Clostridioidesdifficile diarrhea reflective of the vaccine! 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