The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, causing coronavirus disease 2019 (COVID-19), has presented many challenges and spurred intense investigations into the pathogenesis of this disease. In addition to respiratory disease, many patients with SARS-CoV-2 infection are experiencing systemic illnesses, including kidney failure, heart failure, liver injury, neurologic dysfunction, and skin manifestations (eg, COVID toe). The etiology and pathogenesis of these sequelae are the current focus of intense research and speculation. A fundamental question is whether the extrapulmonary disease processes encountered in COVID-19 patients result from direct infection of target organs or indirect injury, resulting from initially localized infection in the lungs and upper respiratory tract and subsequent systemic responses, such as cytokine release/cytokine storm. Viruses come in all shapes and sizes but are invariably small and require an electron microscope to resolve the morphology of individual particles.
With the emergence of SARS-CoV-2, we are witnessing a renaissance in the use of electron microscopy (EM) to help identify virally infected cells and uncover the pathogenesis of this disease. Several articles have used EM to propose direct evidence of infection of the kidney
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and other tissues
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by SARS-CoV-2. These reports have fueled speculation that direct infection of tissues throughout the body contributes to the morbidity and mortality of COVID-19.
Unfortunately, many of these studies are fraught with confusion over differentiating virus from normal structures within cells, and hence there has been an explosion of misinformation. Indeed, published articles claiming to provide direct evidence of SARS-CoV-2 virus infection in kidney cells and endothelial cells have provoked letters to the editor challenging these claims.
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In this perspective, we will discuss what is known about coronavirus infection and some of the basic ultrastructural cell biology that has been confused for coronavirus infection of cells (namely, the machinery that controls endocytosis and exocytosis and membrane transport within cells).
