eCollection 2022 Jul. Fever duration was longer in patients 6 to 12 months old and 12 to 18 . eCollection 2022. 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). Ying-Hao P, Yuan-Yuan G, Hai-Dong Z, Qiu-Hua C, Xue-Ran G, Hai-Qi Z, Hua J. Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever. Careers. 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 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). In many cases, no specific cause of the fever is found, 2 . Prolonged fever is associated with adverse outcomes in dengue viral infection. bOnly 1 sample of paired values available. Fevers usually don't need treatment. Seven more confirmed cases of novel coronavirus infection in Singapore.2020. 2017 Jun 22;4(3):ofx133. An official website of the United States government. Potentially diagnostic clues should be sought during the history and physical examination to guide further evaluation of prolonged febrile illness. The site is secure. QJM. Patients with saddleback fever appeared to have good outcomes regardless of the fever. 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. 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. sharing sensitive information, make sure youre on a federal Lohr JA, Hendley JO. National Library of Medicine 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). Available at: Wang D, Hu B, Hu C, et al. PMC 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]. Our cohort only had 1 mortality, and this may be reflective of the overall low mortality rate in Singapore. Statistical analyses were performed with the Mann-Whitney. Communicable Diseases Surveillance in Singapore 2005. 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. This suggests that in patients with prolonged fever, close monitoring for deterioration should be instituted, while patients with saddleback fever who remain well and do not require supplemental oxygenation are unlikely to require close monitoring in the hospital. The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue. Respiratory syncytial virus disease burden in community-dwelling and long-term care facility older adults in Europe and the United States: A prospective study, Viral aetiology and clinical characteristics of acute respiratory tract infections in hospitalized children in Southern Germany (2014-2018), Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People with Treated HIV, Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks, Impact of hypoalbuminemia on ceftriaxone treatment failure in patients with Enterobacterales bacteremia: a propensity matched, retrospective cohort study, About the Infectious Diseases Society of America, https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200430-sitrep-101-covid-19.pdf?sfvrsn=2ba4e093_2, https://www.moh.gov.sg/news-highlights/details/confirmed-imported-case-of-novel-coronavirus-infection-in-singapore-multi-ministry-taskforce-ramps-up-precautionary-measures, https://www.moh.gov.sg/news-highlights/details/seven-more-confirmed-cases-of-novel-coronavirus-infection-in-singapore, https://sso.agc.gov.sg/Act/IDA1976#pr25A-, https://doi.org/10.1101/2020.03.02.20029975, https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-home-care.html, https://www.straitstimes.com/singapore/9-in-10-coronavirus-patients-housed-in-isolation-facilities, https://www.moh.gov.sg/news-highlights/details/56-more-cases-discharged-528-new-cases-of-covid-19-infection-confirmed, http://creativecommons.org/licenses/by-nc-nd/4.0/, Receive exclusive offers and updates from Oxford Academic. eCollection 2013. An official website of the United States government. CMAJ Open. 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). Comparisons between prolonged fever and nonprolonged fever group are summarized in Tables 1 and 2. eCollection 2017 Summer. Pung R, Chiew CJ, Young BE, et al. Plasma immune mediator levels in COVID-19 patients experiencing different fever patterns. Importantly, upregulation of the IL-1 pathway on monocytes can increase prostaglandin E2 expression and drive fever [32]. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (. 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. Roseola symptoms might include: Fever. 2013 Sep 26;7(9):e2412. RSV is a contagious illness that infects the respiratory tract and can lead to more severe infections like pneumonia or bronchiolitis. 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] . FOUR TYPES OF FEVERS - Read online for free. Emadi A, Chua JV, Talwani R, Bentzen SM, Baddley J. Additional references were identified from the articles reviewed. Fever was defined as a temperature of 38.0C. Plasma fractions were isolated from blood samples of COVID-19 patients collected during the acute phase (median post-illness onset, 6 days). Disclaimer. Erythrocyte sedimentation rate and C-reactive protein levels should be measured in the initial workup of a patient who has prolonged febrile illness without a clear source. 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. . J Microbiol Immunol Infect. 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. The results of this study can be used to optimize placement of patients with COVID-19. 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. doi: 10.1371/journal.pntd.0004575. History and physical examination alone are often sufficient to diagnose uncomplicated infectious causes of fever . But there are some important differences. Patients with saddleback fever appeared to have good outcomes regardless of the fever, they noted. 2013 Jul;23(7):463-7. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is presently unknown. For cases with saddleback fever, fever recurred at a median (IQR) of 10 (812) days after symptom onset. Interestingly, there are also higher plasma levels of IL-1RA in patients with prolonged fever compared with control patients. No overall differences in safety or effectiveness . 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. This corroborated well with our findings of increased hypoxia in patients with prolonged fever. Fever of unknown origin (FUO) in adults is one of the most vexing clinical conditions for clinicians and patients. Clipboard, Search History, and several other advanced features are temporarily unavailable. doi: 10.1371/journal.pntd.0002412. Influenza (flu) and the common cold are both contagious respiratory illnesses, but they are caused by different viruses. Additional searches included the Cochrane database, Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, and the National Guideline Clearinghouse. 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. Elevated lactate dehydrogenase levels can be indicative of infectious and malignant causes of FUO, including malaria, lymphoma, and leukemia.15,21 Measurement of ferritin levels may also be helpful.33 An elevated ferritin level in prolonged febrile illness may indicate malignancy (especially myeloproliferative disorders) and other noninfectious inflammatory diseases, such as systemic lupus erythematosus or temporal arteritis.21,33 One study established a ferritin level of 561 ng per mL (1,261 pmol per L) as the optimal cutoff value to predict that FUO was due to a noninfectious cause.22 Extreme elevation of ferritin levels (greater than 1,000 ng per mL [2,247 pmol per L]) can point to adult Still disease.34 Infection is the most common reason ESR is extremely elevated, but if there is no evidence of infectious causes, clinicians should consider malignancy, renal disease, and inflammatory disorders if the ESR is 100 mm per hour or greater.29. Confirmed imported case of novel coronavirus infection in Singapore; multi-ministry taskforce ramps up precautionary measures. Recommendations of the Scientific Working Group on Dengue. The analysis, which was. The higher levels of IL-1 could initiate the first occurrence of fever, while the pro-inflammatory cytokines IL-21 and IL-22 mediate the activation of T cells and M1 macrophages [25, 26], which drive the recurrence of fever in saddleback fever cases. doi: 10.1371/journal.pone.0167025. CONCLUSIONS: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. 2022 Aug;14(8):321-326. doi: 10.14740/jocmr4791. Saddleback fever was significantly associated with hypoxia (14.3% vs 0.9%; P=.03) but not ICU admission (0.9% vs 0.0 %; P=1.00) compared with those in the control group. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P=.05). However, unlike RA, rheumatic . Cytokines were determined with multiplex View PDF Save to Library 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). People who wish to treat a fever can try over-the-counter anti-fever medications, such as acetaminophen, aspirin, or ibuprofen. Never give a child aspirin, as this increases the risk of . Outcomes of patients with COVID-19 in the intensive care unit in Mexico: A multicenter observational study. A. In patients with saddleback fever, higher levels of IL-1, IL-21, IL-22, and SDF-1 were observed compared with control patients. Please enable it to take advantage of the complete set of features! In addition, the contribution of immunosenescence toward the establishment of cytokine storm and severe illness can be seen in previous studies [5]. 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). The https:// ensures that you are connecting to the A standardized template was used for recording daily signs and symptoms, vital signs, and management. 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. FOIA 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. This circadian rhythm may differ among individuals but should be consistent in each person . A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Patient information: See related handout on fever of unknown origin in adults, written by the authors of this article. 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. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF. Fever often occurs in response to infection, inflammation and trauma. 2021 Mar 8;9(1):E181-E188. aInvestigations were repeated at the point at which they satisfied criteria for prolonged or 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. In hypoxic conditions, it can trigger the expression of chemokines that attract neutrophils and monocytes to the ischemic tissue [31]. eCollection 2016 May. The site is secure. A dysregulated immune response in COVID-19 has been postulated to lead a deleterious cytokine storm [12]. Since its first report in Wuhan, China, in December 2019, COVID-19 has rapidly spread, becoming a pandemic with more than 3 million confirmed cases [1]. Interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease 2019 (COVID-19). Retrospective characterisation and outcome of surgical treatment for cervical lymph node abscessation in 15 dogs. All authors: no reported conflicts of interest. The Wilcoxon signed-rank test was used to evaluate for differences in paired samples. IL-1 is a pyrogenic cytokine that plays a central role in inflammatory diseases like arthralgia [23]. COVID-19 and sinus infections share several symptoms like nasal congestion, fever, and coughing. PLoS Negl Trop Dis. Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Testing for antinuclear antibodies, rheumatoid factor, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, purified protein derivative (or interferon-gamma release assay), and antineutrophil cytoplasmic antibodies, as well as measurement of the creatine kinase level, can suggest other infectious sources and common noninfectious inflammatory disease etiologies, such as systemic lupus erythematosus, rheumatoid arthritis, and vasculitides. This suggests that in patients with prolonged fever, close monitoring for deterioration should be instituted, while patients with saddleback fever who remain well and do not require supplemental oxygenation are unlikely to require close monitoring in the hospital, explained Ng and co-authors. 2014; 8: e2777 10.1371/journal.pntd.0002777 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. The 2011 dengue haemorrhagic fever outbreak in Lahore - an account of clinical parameters and pattern of haemorrhagic complications. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous. 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. 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. Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study. We also excluded 4 patients whose fever pattern did not fulfill the case definition for prolonged or saddleback fever. Coronavirus disease 2019 (COVID-19) situation report101. Prolonged fever in children: review of 100 cases. A, Heatmap showing the relative concentration of cytokines across patients with different fever patterns. The variance between the highest and lowest core temperature in a given day is usually no more than 1 to 1.5C. Higher respiratory rate, lower SpO2, and lower systolic BP were also associated with saddleback fever compared with the control group. Blue and red represent low and high concentrations, respectively. Differences Between Prolonged Fever and Nonprolonged Fever Groups. Accessibility doi: 10.9778/cmajo.20200250. -. J Biomed Sci. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. Further testing should include blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies. HHS Vulnerability Disclosure, Help 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) Chi-square and Fisher exact tests were used to evaluate differences in proportions for categorical variables, while the Mann-Whitney U test was used to evaluate differences in medians for continuous variables. The results of these microbiological investigations were also collected and analyzed. Fever of unknown origin has been described as a febrile illness (temperature of 101F [38.3C] or higher) for three weeks or longer without an etiology despite a one-week inpatient evaluation. Saddleback fever cases were also found to have higher pro-inflammatory IL-1, T-cell-activating mediators IL-21 and IL-22, and chemokine stromal cellderived factor 1 (SDF-1) compared with controls (Figure 1B). This content is owned by the AAFP. Hypoxia was defined as requirement for supplemental oxygen. 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. 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. 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. Pediatrics 1975; 55:468. Clinical and laboratory predictive markers for acute dengue infection. Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Handout on fever of unknown origin ( FUO ) in adults is one of complete! Wilcoxon signed-rank test was used to optimize placement of patients with different difference between prolonged fever and saddleback fever. Ramps up precautionary measures 9 ): E181-E188 and drive fever [ ]. Among individuals but should be consistent in each person we also excluded patients! Fever patterns share several symptoms like nasal congestion, fever, they noted diagnostic clues should be consistent each... 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