Emerging Viral Infections (ZIKV, SARS-CoV-2, and MPXV) and Depression: Ketamine and (S, R)-Ketamine as Promising Antidepressants.

Emerging viral pathogens, newly reported or rapidly evolving viruses, are a significant public health concern worldwide. Beyond their characteristic clinical presentations, emerging viruses, such as monkeypox virus (MPXV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been increasingly implicated in the development of various neuropsychiatric complications including depression, mainly due to their ability to induce neuroinflammation, immune dysfunction, and neurotransmitter imbalances. Depression is a common mental health condition characterised by continuous low mood or sadness, pessimism, anxiety, and even a tendency to suicide as the main symptoms. Post viral depression commonly shows significant challenges, as traditional antidepressant agents exhibit suboptimal efficacy and prolonged onset of action. Regarding this, ketamine and its enantiomers, S-ketamine and R-ketamine, have recently received increasing attention as potential options in light of their potent and effective antidepressant properties. The present review describes the underlying pathophysiological mechanisms of depression associated with emerging viruses, highlighting the role of neuroinflammation and disturbances inneurotransmitter systems. It also discusses the antidepressant mechanisms of ketamine and its enantiomers, the current clinical evidence demonstrating their effectiveness and safety, especially in the case of treatment-resistant depression, and their growing relevance for mood complications linked to emerging viral infections, including depression. Although preliminary reports propose effectiveness, additional studies are needed to present optimal treatment strategies, long-term safety, and incorporation into clinical practice. Addressing these challenges will be critical for optimising the effectiveness of ketamine- and (S, R)-ketamine-containing therapeutic protocols in treating depression linked to emerging viral infections.