Neurological symptoms may persist for over one year in long-COVID patients

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A new study published in Annals of Clinical and Translational Neurology found that patients who have recovered from coronavirus disease 2019 (COVID-19), reported long-COVID symptoms, and did not require hospitalization during the infection are likely to experience persistent neurologic symptoms, fatigue, and compromised quality of life (QoL) for a median of 14.8 months following their initial infection.

Study: Evolution of neurologic symptoms in non-hospitalized COVID-19 “long haulers.” Image Credit: fizkes /


Despite recent advancements that have been made in the diagnosis, treatment, and prevention of COVID-19, combined with the approval and widespread distribution of numerous targeted vaccines, the long-term impacts of the disease have yet to be defined.

Many patients who have experienced a prolonged infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have subsequently been diagnosed with pulmonary, cardiac, gastrointestinal, and neurologic dysfunctions. These individuals are often referred to as “long-haulers,” with long-term COVID-19-related symptoms collectively referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or long-COVID syndrome.

In addition to this subset of patients, some individuals who have experienced mild respiratory symptoms in the acute phase of the infection, as well as those who did not have a history of pneumonia- or hypoxemia-related hospitalization, will also present with neurological manifestations of PASC (Neuro-PASC). Most long-COVID studies have included COVID-19 patients with a history of the previous hospitalization; however, the long-term impacts of SARS-CoV-2 infection in non-hospitalized patients remain largely unknown.

Furthermore, the effects of COVID-19 vaccines on long-COVID remain obscure.

About the study

In the current study, 50 patients without a history of hospitalization were selected from a pool of COVID-19 patients, along with 50 individuals who were negative for COVID-19 who served as controls.

These 100 patients were monitored for six to nine months to track the occurrence and resolution of cognitive function, which is responsible for the documented “brain fog” reported in long-COVID, along with self-reported QoL. Patient-perceived recovery, cognition, and fatigue were also characterized in vaccinated and unvaccinated individuals.

Study findings

At a median of 9.2 months after their initial COVID-19 diagnosis, no significant change was reported in the frequency of COVID-19-related neurological and non-neurological symptoms. Ultimately, the researchers found that the continued symptom burden of long-COVID persisted for a median of 14.8 months after the onset of symptoms.

Due to the extended duration of their long-COVID symptoms, over 50% of the long haulers in this study tried various therapies to attenuate their symptoms, some of which included alternative/supplements, neuropathic analgesics, and antidepressants. Meanwhile, anosmia and dysgeusia reduced over time, thus suggesting spontaneous resolution of olfactory and gustatory dysfunction.

Nevertheless, marked increases in heart rate and blood pressure abnormalities, as well as gastrointestinal symptoms, were reported during the follow-up period. Continued cytokine release or other viral-mediated mechanisms were speculated as probable causes for this autonomic dysfunction, as these factors are likely responsible for these symptoms.

Overall, both COVID-19-positive and COVID-19 negative individuals reported improvements in their subjective impression of recovery, which was significant in the COVID-19-positive patients. Symptomatic medication use, resolution of anosmia and dysgeusia, as well as a reduction in symptom severity may have contributes to the patients’ perceived improvements.

As compared to their initial clinic visit, both COVID-19-positive and COVID-19-negative patients reported improved cognitive function and decreased fatigue at their follow-up visit. Despite these apparent improvements, both groups reported significantly worse QoL scores for both cognitive function and fatigue as compared to median scores of the general U.S. population. Notably, low cognitive function scores were significantly associated with worse fatigue, anxiety, depression, and sleep disturbances.

Both vaccinated and unvaccinated individuals, which consisted of 40 and 10 individuals, respectively, reported improved subjective impressions of their recovery at the follow-up visit. While vaccinated individuals exhibited a significant improvement in their cognitive function scores at follow-up, neither vaccinated nor unvaccinated individuals exhibited any improvements in their fatigue scores.


Long-COVID continues to cause a detrimental impact on the QoL of many people throughout the world. The current study demonstrated that patients suffering from long-COVID continue to experience various neurological symptoms for over a year after recovering from their initial infection. These findings emphasize the need for researchers to conduct additional studies to better understand the mechanisms responsible for these persistent neurological symptoms in long-COVID patients.

It should be noted that the results reported in the current study were derived from patients infected by early SARS-CoV-2 strains. Nevertheless, these results could prove useful in determining the potential long-term impacts of infection with more recent SARS-CoV-2 strains.

Journal reference:
Nidhi Saha

Written by

Nidhi Saha

I am a medical content writer and editor. My interests lie in public health awareness and medical communication. I have worked as a clinical dentist and as a consultant research writer in an Indian medical publishing house. It is my constant endeavor is to update knowledge on newer treatment modalities relating to various medical fields. I have also aided in proofreading and publication of manuscripts in accredited medical journals. I like to sketch, read and listen to music in my leisure time.


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