The pandemic outbreak of highly contagious coronavirus (COVID-19) became a major threat to our physical health. Meanwhile, the rapid spreading of COVID-19 and related countermeasures (particularly lockdowns) negatively affected our mental wellbeing, due to disease progression-induced fear and fatigue, social distancing and isolation, family conflicts during quarantine, supply shortages, unemployment, and increased financial burden. Accumulating evidence suggest that stress is associated with increased susceptibility to and severity of viral infection, which can be at least partially explained by systemic changes in anti-viral innate and adaptive immunity, as well as dysregulated inflammatory and autoimmune responses. In addition, pandemic-related psychological stress may influence the efficacy of viral vaccines. Thus, deciphering the underlying molecular links between psychological stress and viral infection-associated immune-inflammatory alternations will provide novel insights to the development of optimal therapeutic interventions and prophylactic vaccines.