Reply to: Neurofilament Light Chain in Patients with COVID‐19 and Bacterial Pneumonia

Dear Editor

We read with great interest the letter of Chung HY et al ¹ in which they refer to our recent publication in the Annals of Neurology on “Serum Neurofilament Light Chain Levels in the Intensive Care Unit: Comparison between Severely Ill Patients with and without Coronavirus Disease 2019.” ²

The authors compared plasma neurofilament light chain (pNfL) levels in patients with bacterial and coronavirus disease 2019 (COVID‐19) pneumonia; pNfL levels in bacterial pneumonia 3 days after onset of sepsis were considerably higher than those in COVID‐19 pneumonia at days 3 and 7.

Chung and colleagues concluded that their results are corroborated by those of others ³ , ⁴ showing “low to intermediate NfL levels in COVID‐19 patients as compared to other infectious diseases…” and that their “own data and current evidence do not indicate commonly occurring neuronal damage in COVID‐19.” Noteworthy, the clinical severity of patients with COVID‐19 pneumonia by Chung HY et al were lower with a mean Sequential Organ Failure Assessment (SOFA) score of 4, whereas in our cohort it was 7; 86% of the critically ill patients in our study were ventilated and 17% died (no data are provided about eg, ventilation, comorbidities, intensive care unit [ICU] admission, oxygenation indexes, and outcome in patients with COVID‐19 in the cohort of Chung HY et al). In contrast to our cohort, which was analyzed after disease progression that led to an admission to the ICU (ie, representing a later stage of the disease), the patients presented by Chung HY et al were analyzed within the first few days after onset of pneumonia. In fact, the patients with COVID‐19 described by us match better with the subgroup categorized as “severe” by Kanberg et al ³ where the median pNfL level was 32.7 pg/ml, very similar to our finding of 36.1 pg/ml in serum (vs approximately 5–10 pg/ml in Fig 1C of Chung HY et al). We consider these levels not as “low to intermediate” as they are in the range of patients with bacterial pneumonia presented by Chung HY et al.

Patients with sepsis‐associated encephalopathy show radiological signs of brain damage and neuropsychological signs of brain dysfunction, ⁴ pNfL levels were strongly increased compared to patients without brain dysfunction; further, they correlated with a poorer long‐term neurofunctional outcome. Neuronal damage can be assumed as the cause for the elevation of serum neurofilament light chain (sNfL) observed by Chung et al in their cohort with bacterial pneumonia. Important in our view is the observation that neuronal damage occurs in the course of both COVID‐19 and sepsis‐associated encephalopathy (ie, also in absence of overt infection of the central nervous system). ⁴ , ⁵ We agree that neuronal damage is not specific for COVID‐19, but seems likely a generic consequence in severe infectious disease of various etiologies. We agree as well that the role of renal dysfunction and other metabolic changes as factors modulating NfL levels during infectious diseases needs to be explored.

Potential Conflicts of Interest

The authors declared no conflict of interest.