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The COVID-19 pandemic remains an evolving disease posing a challenge of incomplete understanding escalated by random atypical clinical presentations. Numerous challenges still exist with accessibility and availability of standard COVID-19 viral testing using real-time Polymerase Chain Reaction (RT-PCR), in low- and middle-income countries, especially in several hospital settings. The clinical information of three select patients at a major health facility in Southwestern Nigeria with unusual COVID-19 clinical presentation and clinical management dilemma related to challenges with COVID-19 viral laboratory testing, were retrospectively reviewed. The medical history in all three cases closely mimicked that of other medical conditions because of assumptions created by red herrings like an acute exacerbation of an underlying non-communicable disease (diaphragmatic eventration) in case 1, re-activation of a previously treated lung condition (tuberculosis) in case 2 and a sequalae of a previously diagnosed but poorly-managed chronic non-communicable disease (decompensated hypertensive heart disease). Also, viral testing was challenging in all cases due to reasons ranging from late turn-around time to inconsistent results. However, thoracic imaging was employed in all cases to heighten suspicion of COVID-19 infection, resolve management dilemma and limit intra-hospital spread. Thoracic imaging can play a major role within hospital settings in low-and middle-income countries in resolving diagnostic challenges of atypical COVID-19 clinical presentations, raising suspicion for early institution of intra-hospital disease containment measures, limiting exposure among hospital staff and guiding clinical case management of COVID-19; especially where challenges with confirmatory viral testing remain persistent., Competing Interests: The authors declare no competing interests., (Copyright: Ademola Joseph Adekanmi et al.)