Severe Disease, Azithromycin, and Depression Predictors of Post-COVID-19 Pain

Scientists working in the laboratory
In a case-control study, researchers assessed risk factors for persistent neuropathic pain in those who have recovered from COVID-19 and observed their serum level of neurofilament light chain.

High serum neurofilament light chain (NfL) may be a potential biomarker for persistent post-COVID-19 pain. These findings were published in Pain Medicine.

People who overcome COVID-19 infection and reach full recovery can still struggle with residuals like post-COVID-19 cognitive and physical fatigue. Currently, there are no data related to pain in patients during post-COVID-19 recovery. Researchers do believe NfL can serve as a biomarker for screening and follow-up of neuro-axonal injury. The objective of the current study was to assess risk factors for persistent neuropathic pain in patients recovered from COVID-19 and observe their serum NfL levels and how it relates to pain intensity.

Patients (n=45) and health care workers (n=45) who had recovered from COVID-19 were recruited at the Beni-Suef University Hospital in Egypt between September and November 2020 for this case-control study. The patients were seeking medical care for persistent pain postinfection and the health care workers who recovered from infection without pain were recruited as age- and gender-matched controls. Study participants were evaluated for pain symptomology, depression status, and for potential serum biomarkers.

Patients and control individuals were a mean age of 43 (standard deviation [SD], 15.85) and 45.71 (SD, 13.89) years, 66.7% and 64.4% were women, and 75.6% and 71.1% had no comorbidities, respectively. At baseline, the patients had higher instances of depression (26.7% vs 8.9%; P =.027), moderate (46.7% vs 26.7%) or severe (28.9% vs 13.3%) COVID-19 (P =.003), they had a longer duration of illness (median, 18 vs 14 days; P =.001), and more received azithromycin (82.2% vs 46.7%; P <.001).

Among those with post-COVID-19 pain, most had pain in their arms and legs (66.7%) and median pain was 8 (interquartile range [IQR], 6-9) points on the Visual Analogue Scale. Pain manifested as a feeling of electric shock (37.8%), burning (33.3%), painful cold (13.3%), burning and electric shock (11.1%), or burning and painful cold (4.4%).

This group also had higher serum NfL (mean, 11.34 vs 7.64 pg/ml; P =.029). Stratified by allodynia status, higher NfL was observed among the cohort with allodynia pain (mean, 14.96 vs 9.14 pg/ml; P =.05). Pain scores were correlated with NfL concentration (r, 0.484; P =.001).

Predictors of post-COVID-19 pain included severe infection (odds ratio [OR], 6.276; 95% CI, 1.134-34.729; P =.035), receiving azithromycin (OR, 5.444; 95% CI, 1.631-18.169; P =.006), moderate infection (OR, 4.901; 95% CI, 1.309-18.348; P =.018), and depression (OR, 4.462; 95% CI, 1.073-18.553; P =.04).

This study was limited by not including serum NFL into the logistic regression to detect predictors for post-COVID-19 pain.

These data indicated that post-COVID-19 pain associated with disease severity, depression status, and receiving azithromycin.

“Serum NFL may serve as a potential biomarker for persistent neuropathic pain after COVID-19,” the researchers concluded.

Additional independent study is needed to confirm these findings.


Magdy R, Eid RA, Fathy W, et al. Characteristics and Risk Factors of Persistent Neuropathic Pain in Recovered COVID-19 Patients. Pain Med. Published online December 21, 2021. doi:10.1093/pm/pnab341