Persistent SARS-CoV-2 infection: significance and implications

The study “Persistent SARS-CoV-2 infection: significance and implications” delves into the complexities and challenges posed by prolonged SARS-CoV-2 infections, especially in immunocompromised individuals. These persistent infections represent a significant clinical and public health concern due to their potential role in the emergence of novel virus variants through ongoing viral replication and evolution.

Key Points from the Study:

  1. Evidence of Persistent Infections: While most people clear SARS-CoV-2 from their respiratory tract after an acute infection, a subset experiences prolonged infections. These are characterized by ongoing viral replication in at least one anatomical site and can last for extended periods, with some cases showing viral persistence for up to 500 days. Such prolonged infections can lead to within-host evolution of the virus, contributing to the emergence of new variants.
  2. Clinical Challenges: Persistent SARS-CoV-2 infection lacks a broadly accepted case definition, complicating the understanding of its clinical features, prevalence, and risk factors. The study proposes more inclusive case definitions and highlights the diverse clinical presentations of persistent infections, ranging from asymptomatic or paucisymptomatic to chronic, with ongoing or progressive symptoms.
  3. Under-ascertainment and Risk Factors: Persistent infections are likely under-detected, with immunocompromised individuals at higher risk. Studies have shown a significant percentage of patients with hematological malignancies and other conditions exhibit prolonged viral RNA shedding.
  4. Impact on Viral Evolution and Transmission: Persistent infections in immunocompromised hosts offer a unique environment for SARS-CoV-2 to evolve immune escape mutations and other adaptive changes. Such environments have been hypothesized as the breeding grounds for variants of concern, including alpha and omicron, demonstrating the significance of persistent infections in the virus’s evolution.
  5. Potential Tissue Reservoirs and Cryptic Lineages: The study explores the idea that SARS-CoV-2 may establish reservoirs in tissues beyond the respiratory tract, contributing to persistent infections. Additionally, cryptic lineages detected in wastewater, showing extensive genetic divergence, suggest that persistent infections may contribute to the viral genetic pool in unexpected ways.
  6. Management and Research Gaps: Current treatment and diagnostic approaches for persistent SARS-CoV-2 infection are inadequate, underlining the need for targeted research to develop effective interventions. The study calls for the development of animal models to study persistent infections, improved diagnostic criteria, and comprehensive treatment guidelines.
  7. Public Health Implications: Addressing persistent SARS-CoV-2 infections is crucial for preventing the emergence and spread of new variants. Enhanced surveillance, both in clinical settings and through environmental monitoring like wastewater analysis, is recommended to better understand and manage these infections.


The study underscores the urgent need for a concerted effort in research, clinical management, and public health strategies to address persistent SARS-CoV-2 infections. By improving our understanding of these infections, developing effective diagnostics and treatments, and implementing robust surveillance, we can mitigate the risks associated with persistent infections and their role in the evolution of SARS-CoV-2.

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