Insights into Persistent SARS-CoV-2 Reservoirs in Chronic Long COVID

Area of Science:

• Immunology
• Virology
• Pathology

Background:

• Long COVID (LC) affects millions globally, presenting over 200 diverse symptoms impacting multiple organ systems.
• Current treatments for LC are lacking, leading to significant long-term health and economic burdens.
• The heterogeneity of LC symptoms and lack of diagnostic biomarkers challenge treatment development.

Purpose of the Study:

• To review the evidence for persistent virus and viral RNA (vRNA) reservoirs in Long COVID patients.
• To explore mechanisms of inflammation, immune evasion, and immune overstimulation in LC.
• To discuss potential T cell immunotherapeutic strategies for managing persistent viral reservoirs in LC.

Main Methods:

• Review of studies detecting persistent virus/vRNA directly or indirectly via immune responses in LC patients.
• Analysis of proposed mechanisms driving chronic inflammation and organ damage in LC.
• Examination of animal models relevant to viral reservoirs in LC.
• Discussion of T cell-based immunotherapeutic approaches.

Main Results:

• Persistent virus/vRNA reservoirs are detected in various tissues of LC patients, correlating with chronic symptoms.
• These reservoirs may drive chronic inflammation, immune evasion, and T cell exhaustion.
• Animal models support the role of viral reservoirs in LC pathogenesis.

Conclusions:

• Persistent viral reservoirs are a significant factor in Long COVID pathogenesis, contributing to chronic inflammation and diverse symptoms.
• Targeting these reservoirs with T cell immunotherapies presents a promising strategy for mitigating LC severity.