Characterizing Viral Infection by Electron Microscopy: Lessons from the Coronavirus Disease 2019 Pandemic

Shreeram Akilesh1, Roberto F Nicosia1, Charles E Alpers1

  • 1Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.

Insights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is found in kidneys, but direct infection of these organs is difficult to prove. This perspective clarifies electron microscopy criteria for identifying SARS-CoV-2 in extrapulmonary tissues.

Area of Science:

  • Virology
  • Pathology
  • Microscopy

Background:

  • The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread illness and mortality.
  • Viral RNA detection in extrapulmonary organs, including the kidney, suggests potential direct infection beyond the lungs.
  • Demonstrating direct SARS-CoV-2 infection in tissues outside the lung has remained a challenge.

Purpose of the Study:

  • To discuss current knowledge of coronavirus infection in extrapulmonary tissues.
  • To differentiate true viral infection from artifactual cellular structures observed via electron microscopy.
  • To establish rigorous criteria for identifying viral pathogens using electron microscopy.

Main Methods:

  • Review of existing literature on SARS-CoV-2 infection and electron microscopy.
  • Analysis of ultrastructural cell biology relevant to viral identification.
  • Development of a framework for rigorous pathogen identification in tissues.

Main Results:

  • Misinterpretation of electron microscopy findings has complicated the assessment of extrapulmonary SARS-CoV-2 infection.
  • Basic cellular ultrastructure can be mistaken for viral particles.
  • Clear, rigorous criteria are needed to confirm viral presence.

Conclusions:

  • Accurate identification of SARS-CoV-2 in extrapulmonary tissues requires strict adherence to established electron microscopy criteria.
  • Distinguishing viral infection from cellular artifacts is crucial for understanding the full scope of SARS-CoV-2 pathogenesis.
  • Standardized methods will improve the reliability of research on viral dissemination.

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