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Keeping Your Diagnostic Mind Open During the COVID-19 Pandemic

Siberry, George K. MD, MPH

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The Pediatric Infectious Disease Journal: December 2020 - Volume 39 - Issue 12 - p e444
doi: 10.1097/INF.0000000000002951
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As coronavirus disease 2019 (COVID-19) has surged through different parts of the country (and world) this year, clinicians have had to quickly learn both the typical and unusual manifestations of this new disease. Months into the pandemic, the recognition of multisystem inflammatory syndrome in children (MIS-C) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children was a stunning example of how astute pediatricians considered the possibility of a new manifestation of COVID-19, even as they considered Kawasaki and other known inflammatory causes of similar syndromes.

As clinicians increasingly appreciated the extremely wide range of illness resulting from SARS-CoV-2 infection—from no symptoms at all to severe and fatal illness and from typical respiratory illnesses to involvement of nearly any organ system—the natural tendency may have been to attribute most acute illnesses to COVID-19. Many of us remember the guidance we often heard during our medical training: atypical presentations of common diseases are more common than typical presentations of uncommon diseases. COVID-19 would naturally be in the differential diagnosis for a wide range of illnesses when community transmission burden is high.

However, clinicians must be committed to keeping an open mind to alternative diagnoses, even as they are inundated by this pandemic. In this issue of the Journal, we see 2 illustrative examples of the importance of this principle.

Alamaret et al1 describe a series of 6 children presenting to their Houston center with a syndrome with of fever, rash, and elevated inflammatory markers. Despite negative virologic testing for SARS-CoV-2, antiinflammatory treatment for potential MIS-C was undertaken, but the clinicians explored another potential (and treatable) diagnosis. With assistance from infectious disease colleagues, they elicited exposure histories for dogs and fleas that led the multidisciplinary team to suspect murine typhus, a seasonally endemic infection in that part of Texas, and to treat the patients successfully with doxycycline—even before serologic testing confirmed the diagnosis. As the authors eloquently note, “Diagnostic dilemmas during times of great uncertainty highlight the importance of multidisciplinary collaboration when evaluating patients to avoid biased early closure of diagnoses toward diseases that are dominating the conversation.”

Repper et al2 describe a 17-year-old girl who presented with fever, sore throat, lymphadenopathy, multifocal pneumonia, and elevated inflammatory markers that led to several diagnostic concerns, including SARS-CoV-2 infection. Nasopharyngeal PCR testing for SARS-CoV-2 was negative. Following development of tachycardia and hypotension, the patient underwent an echocardiogram that revealed low-normal ejection fraction and dilatation of the left main and left anterior descending coronary arteries. These findings made the clinicians more concerned about MIS-C, but they kept their diagnostic thinking appropriately broad, including the Lemierre syndrome that had been on their differential diagnosis from the beginning—and that growth of Fusobacterium necrophorum on blood culture helped to confirm. Indeed, this was a case of a typical presentation of an uncommon disease. As the authors conclude: “This case affirms that pediatricians and subspecialists taking care of acutely ill patients in the era of COVID-19 should continue to remain vigilant when faced with elusive clinical presentations and remember that ‘not all that glitters is gold.’”

Even in the throes of a pandemic ... all fever and severe illness is not COVID-19.


The contents in this article are those of the author and do not necessarily reflect the view of the US President’s Emergency Plan for AIDS Relief, the US Agency for International Development, or the US Government.


1. Alamarat Z, Pérez N, Wootton S, et al. Murine typhus outbreak 1 presenting as multisystem inflammatory syndrome in children during SARS-CoV-2 pandemic. Pediatr Infect Dis J. 2020;39:e447–e449.
2. Repper DC, Arrieta AC, Cook JE, et al. A case of Lemierre syndrome in the era of COVID-19: all that glitters is not gold. Pediatr Infect Dis J. 2020;39:e445–e447.
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