The analysis, which was. 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]. Trials. For cases with saddleback fever, fever recurred at a median (IQR) of 10 (812) days after symptom onset. Keywords: 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. Patients with saddleback fever appeared to have good outcomes regardless of the fever. Your comment will be reviewed and published at the journal's discretion. Front Cell Infect Microbiol. 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. 2022 Oct 31;12:1009894. doi: 10.3389/fcimb.2022.1009894. official website and that any information you provide is encrypted 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). 2017 Jun 22;4(3):ofx133. 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 (. . IL-1RA is naturally secreted by human hosts to limit the activity of IL-1 during hyperinflammation [22]. Please check for further notifications by email. Fever was defined as a temperature of 38.0C. sharing sensitive information, make sure youre on a federal 2013 Oct 20;20(1):75. doi: 10.1186/1423-0127-20-75. sharing sensitive information, make sure youre on a federal as they fulfilled overlapping criteria for prolonged and saddleback fever. If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield. A lower IP-10 level is consistent with the finding that saddleback fever cases tend to have better clinical outcomes than prolonged fever cases. Patients who tested positive were not discharged until they had 2 negative PCR tests 24 hours apart [13]. Prolonged fever of unknown origin: a record of experiences with 54 childhood patients. -. ELIZABETH C. HERSCH, COL, MC, USA, AND C. ROBERT, OH, LTC, MC, USA. 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 Both prolonged fever and saddleback fever were not significantly associated with mechanical ventilation as compared with the control group (Table 1). Pediatrics 1975; 55:468. One limitation of the study is the small sample size of our cohort. 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]. A fever is a rise in body temperature. Repeat CXR was not performed for cases in the control group and 1 case of saddleback fever. 2016 Dec 9;11(12):e0167025. Flu is caused by influenza viruses only, whereas the common cold can be caused by a number of different viruses, including rhinoviruses, parainfluenza, and seasonal coronaviruses. Coronavirus disease 2019 (COVID-19) situation report101. The 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern of haemorrhagic complications. 2022 Dec;55(6 Pt 1):1044-1051. doi: 10.1016/j.jmii.2022.07.009. However, unlike RA, rheumatic . The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. Please enable it to take advantage of the complete set of features! Outcomes of patients with COVID-19 in the intensive care unit in Mexico: A multicenter observational study. The Author(s) 2020. Rowe EK, Leo Y-S, Wong JGX, Thein T-L, Gan VC, Lee LK, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. If the diagnosis remains elusive, 18F fluorodeoxyglucose positron emission tomography plus computed tomography may help guide the clinician toward tissue biopsy. One case with prolonged fever had concomitant infection with ventilator-associated pneumonia, with Klebsiella pneumoniae grown from his endotracheal aspirate on day 8 of ICU admission (day 15 of illness). Additional searches included the Cochrane database, Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, and the National Guideline Clearinghouse. Bethesda, MD 20894, Web Policies 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. Outcomes of interest were hypoxia, admission to the intensive care unit (ICU), need for mechanical ventilation, and mortality. doi: 10.1093/omcr/omac079. A. 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. 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. Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. Rheumatic fever mostly affects children aged 5-15 years, but it is rare in adults and children aged under 3 years. In one review, an ESR of 100 mm per hour or greater had a high specificity for malignancy (96%) and infection (97%), and its positive predictive value was 90%.29 A normal ESR has a high negative predictive value for temporal arteritis.28,30 An ESR that is not elevated has no diagnostic value and does not rule out neoplastic or other disorders.27 CRP level is a sensitive marker for infection and inflammation, but it is not sensitive enough to discriminate between disease processes.28 However, a more recent prospective study found that the chance of establishing a diagnosis was higher in patients who had an elevated CRP level and ESR.15, Procalcitonin is a newer marker specific for bacterial infection. Federal government websites often end in .gov or .mil. bOnly 1 sample of paired values available. Lancet 2020; 395:497506. PMC Disclaimer. RSV is a contagious illness that infects the respiratory tract and can lead to more severe infections like pneumonia or bronchiolitis. In many cases, no specific cause of the fever is found, 2 . 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. Khalaf M, Alboraie M, Abdel-Gawad M, Abdelmalek M, Abu-Elfatth A, Abdelhamed W, Zaghloul M, ElDeeb R, Abdeltwab D, Abdelghani M, El-Raey F, Aboalam H, Badry A, Tharwat M, Afify S, Elwazzan D, Abdelmohsen AS, Fathy H, Wagih Shaltout S, Hetta HF, Bazeed SE. CMAJ Open. 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 particular, fever was reported in about 72%98.6% of patients, usually lasting <7 days [4, 710]. 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). People who wish to treat a fever can try over-the-counter anti-fever medications, such as acetaminophen, aspirin, or ibuprofen. Several diagnostic algorithms have been suggested for FUO, but few are supported by evidence from prospective studies.17 Region-specific serologic tests, more advanced radiologic studies, and more invasive diagnostic procedures can be guided by potentially diagnostic clues. Ying-Hao P, Yuan-Yuan G, Hai-Dong Z, Qiu-Hua C, Xue-Ran G, Hai-Qi Z, Hua J. 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). 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. Fever of unknown origin is more often an atypical presentation of a common disease rather than an unusual disease. In multiple studies, procalcitonin has been shown to have a specificity ranging from 70% to 98%, with a higher specificity for bacterial infection than other markers.28,31,32 It may be helpful in distinguishing between fevers with a bacterial cause vs. noninfectious inflammatory diseases, but its role in the workup of FUO is currently undefined.28,32, If the diagnosis remains elusive, tests targeting malignancies and noninfectious inflammatory diseases should be considered. Outcomes of COVID-19 Among High-Risk Individuals: A Study Comparing Febrile and Afebrile Presentation. 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). eCollection 2022 Jul. 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. 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. Before Prolonged fever is associated with adverse outcomes in dengue viral infection. Ahmed S, Mohammad WW, Hamid F, Akhter A, Afzal RK, Mahmood A. J Coll Physicians Surg Pak. Patient information: See related handout on fever of unknown origin in adults, written by the authors of this article. Cytokine level for healthy controls (n=23) is indicated by the black dotted line. Background: Further testing should include blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies. 2021 Mar 8;9(1):E181-E188. To investigate whether the fever patterns experienced by the patients are due to differences in immune responses, concentrations of 45 immune mediators were profiled. 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). Fever is a nonspecific symptom that may be caused by infectious and noninfectious conditions, including malignancies, systemic rheumatic diseases, and drug reactions. Angela Chow Li Ping, Brenda Sze Peng Ang, Chen Seong Wong, Cheng Chuan Lee, Ding Ying, Jun-Yang Tay, Kalisvar Marimuthu, Lawrence Soon U. Lee, Yee-Sin Leo, Li Min Ling, Li Wei Ang, Lin Cui, Mark I-Cheng Chen, Monica Chan, Mucheli Sharavan Sadasiv, Oon-Tek Ng, Pei Hua Lee, Poh Lian Lim, Sapna Pradip Sadarangani, Shawn Vasoo, Stephanie Sutjipto, Tsin Wen Yeo, Tze Minn Mak. Fever was defined as a temperature of 38.0C. 2013 Jul;23(7):463-7. eCollection 2016. A dysregulated immune response in COVID-19 has been postulated to lead a deleterious cytokine storm [12]. Please enable it to take advantage of the complete set of features! In addition to their pro-inflammatory properties, both IL-6 and IP-10 have been reported to be associated with disease severity and ICU admission in COVID-19 [18, 19] . Treatment of fever in adults usually involves ibuprofen, acetaminophen, or aspirin. The differences in cytokine and chemokine profiles among control patients with fever7 days, patients with prolonged fever, or patients with saddleback fever at the early acute phase of illness suggest that different immunological responses could result in the differences in the clinical phenotype observed. The https:// ensures that you are connecting to the Such facilities free up hospital beds to enable sicker patients to be optimally managed. National Library of Medicine 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. The classic presentation is one of fever, malaise, diffuse abdominal pain, and constipation. A fever may be caused by a virus, bacteria, fungus, blood clot, tumor, drug, or the environment. 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. Seven more confirmed cases of novel coronavirus infection in Singapore. The results of this study can be used to optimize placement of patients with COVID-19. 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. 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]. The findings of the study are useful for informing the optimal placement of patients with COVID-19, the researchers pointed out. 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. Hypoxia was defined as requirement for supplemental oxygen. Rash. 2014; 8: e2777 10.1371/journal.pntd.0002777 Accessibility 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. Viruses, bacteria, fungi, and parasites can cause infections. Chan SY, Tsai YF, Yen MY, Yu WR, Hung CC, Kuo TL, Chen CC, Yen YF, Huang SH, Huang TC, Huang SJ. doi: 10.9778/cmajo.20200250. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. Out-of-hospital cardiac arrest and in-hospital mortality among COVID-19 patients: A population-based retrospective cohort study. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. Approximately 12% to 35% of patients die from an FUO-related cause (generally infection or malignancy), yet of those whose conditions remain undiagnosed, most recover or have a benign course with a good prognosis.5,22. 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