Brain Infection and Neuroinflammation in ME/CFS and Post-COVID Encephalitis: A Case-Based Perspective

It ultimately comes down to the brain—what it was, and what it is now.

I recently revisited personal writings from thirty years ago, when I was prescribed SSRIs in 1993 for post-traumatic stress disorder (PTSD), and compared them with work produced during a prolonged illness with COVID-19 in 2021, which was complicated by encephalitis. With the recent improvement in brain function—likely due to reduced inflammation—the contrast is striking.

While taking SSRIs, my cognitive processing seemed trapped in an emotional loop. At the time, I was unaware that my writing had shifted heavily toward narrative expression, while logical reasoning and problem-solving were noticeably impaired. Frequent switching between the two languages I speak often led to grammatical inconsistencies and frequent spelling errors. This phase of unrecognized cognitive symptoms left me reliant on treatments that ultimately proved ineffective.

Remarkably, the abrupt discontinuation of SSRIs in 2000 was associated with neither therapeutic benefit nor withdrawal-related adverse effects. However, as neuroinflammation appeared to resolve, improvements were observed in executive functioning, verbal fluency, and written expression, gradually returning to baseline levels.

Several months ago, I conducted a non-standard sputum culture using a direct Petri dish inoculation method on samples from seven individuals presenting with persistent headache or cognitive dysfunction consistent with Long-COVID-related brain fog. Preliminary microbiological analysis yielded the following isolates: three colonies of Candida species, two isolates comprising Enterococcus and Streptococcus species, and two isolates of Penicillium. These findings suggest the presence of opportunistic or commensal organisms that may warrant further investigation in the context of post-viral neuroinflammatory conditions.

Although limited in scope, these results align with growing evidence of systemic microbial involvement in inflammatory processes. Given the expanding research on neuro-inflammation, I examined these data in the context of central nervous system health. To explore possible mechanisms, I reviewed Dr. Jarred Younger’s investigations into microglial activation, revisited Professor Robert Sapolsky’s lectures on stress-related neurobiology, and analyzed neuroscientist James Fallon’s work on neuropathological traits in psychopathy. These sources were compared with my own observational data collected over years of studying individuals with aggressive behavior and severe physical illness.

A consistent pattern emerged: when the brain is affected by infection or inflammation, symptom severity escalates and cognitive decision-making deteriorates. The Default Mode Network (DMN) is a central player in how the human brain processes internal thoughts, memories, emotions, and self-referential thinking and vulnerable to infection. In this state, individuals become more vulnerable and may desperately pursue unproven or misguided therapeutic interventions.

While organ-specific pathology clearly contributes to disease burden, my observations suggest that insulin-related neuroinflammation and microglial abnormalities—particularly within the bilateral precuneus, regardless of etiology—can profoundly impair executive function, distort judgment, and sustain cycles of dysfunction and physical pain. This raises the question of whether certain presentations of brain inflammation could, in fact, meet the Sequential Organ Failure Assessment (SOFA) criteria currently applied in the diagnosis of sepsis.

From a clinical perspective, this leads to an urgent consideration: how many chronic and debilitating conditions—such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)—could be identified and treated earlier if advanced neuroimaging modalities, such as MRI or PET scans, were performed at the onset of severe, unexplained pain-related or cognitive symptoms? Early detection of brain inflammation and microglial activation could prevent years of ineffective and costly treatments, including psychotherapy, SSRIs, or mindfulness-based interventions, in favor of strategies targeting the underlying neuropathology.

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742