Deep neuroinflammation associated with prolonged COVID

In a recent study posted on medRxiv* Pre-print server, researchers used novel quantitative evaluation, [¹⁸F]DPA-714 positron emission tomography (PET), to be collected in vivo Evidence of extensive neuroinflammation in two patients with post-acute sequel to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC).

Study: Long COVID is associated with widespread in-vivo neuroinflammation [18F]DPA-714 PET. Image Credit: DOERS / Shutterstock

Background

Approximately 36 to 53% of patients with coronavirus disease 2019 (COVID-19) develop persistent chronic symptoms, often referred to as chronic COVID or PASC. These symptoms are primarily neurological and manifest as fatigue, dysgeusia, anosmia, and cognitive impairment.

Although Covid has long affected millions around the world; However, little is known about its pathophysiology. Studies have shown microglial activation and neuroinflammation in the brains of patients with chronic covidosis. So, more in vivo Studies to detect neuroinflammation in COVID-19 patients are needed. This helps to clarify the underlying pathophysiological cascade of neurological symptoms of long covid and to find possible therapeutic treatments.

About the study

In a recent study, researchers asked two study patients to provide informed consent for a detailed investigation. Later, they provided their medical records and participated in standardized neuropsychological assessment tests.

The first patient was a Dutch woman who worked full-time in the late fifties. She was first infected with Covid-19 in December 2020, which was confirmed by a positive reverse transcription-polymerase chain reaction (RT-PCR). In the acute phase of the infection, he did not need hospitalization or treatment. However, he developed persistent fatigue, paroxysm, anosmia, and some visual and concentration loss. Prior to the SARS-CoV-2 infection, she suffered from high cholesterol and fibromyalgia, but her condition was stable and did not interfere with her work. After the infection, her fatigue increased and continued for 15 months (including other symptoms).

The second patient was a Dutch man in the mid-sixties who worked full-time. A positive RT-PCR indicated in March 2020 that he had SARS-CoV-2 infection. During the 15 days he was hospitalized in the acute phase of SARS-CoV-2 infection, he spent one night in the Intensive Care Unit (ICU). For some respiratory problems. He had difficulty concentrating and suffered from severe fatigue after Covid-19. Twenty-four months after the infection, she was declared partially unfit for work while still having symptoms. Both patients were not vaccinated at the time of infection but were vaccinated one year after SARS-CoV-2-infection. One year and 21 months after the infection, they received the relevant primary vaccine series.

The researchers determined the genotype of RS6971 polymorphism in the translocator protein (TSPO) encoding gene. The three healthy control topics of the current study correspond to the study topics that have a high affinity with TSPO. Notably, the first control subjects were a woman, while the subjects were two and three men.

The researchers also included data for a (quantitative) comparison of eight multiple sclerosis (MS) patients. [ ¹⁸F]DPA-714 metabolism. They subjected all study participants to magnetic resonance imaging (MRI), and their [¹⁸F]Scanned with DPA-714 PET arterial blood sample.

Further, the researchers compared [¹⁸F]DPA-714 metabolites in the blood of two chronic COVID patients. Similarly, they compared the brain gray matter BP_ND Values ​​between two long COVID patients and three matching healthy control subjects using 2T4k_V_B Attitude. Finally, they generated volume-of-distribution (V)_T) Images using Logan plot analysis. Using t * = 10 min, they divided those images by the total brain gray matter k1 / k2 ratio, after making a subtraction to correct Logan V._T Images for non-displaceable distribution volume result in BP_ND (= k3 / k4) Images.

Neuroinflammation in two chronic COVID patients. To quantify [18F]Binding to DPA-714 Full-Brain Gray Matter (GM) We used a plasma input two tissue compartment model with blood volume parameter (2T4k_VB). All quantitative total brain gray matter binding capacity (BPND (= k3 / k4)) reported values ​​are estimated using 2T4k_VB. For visualization purposes, we generated volume-of-distribution (VT) images using Logan plot analysis (11), using t * = 10 min, and divided those images by the total brain gray matter k1 / k2 ratio obtained by plasma input 2T4k_VB model. . , After subtraction of 1. In doing so, Logan VT images were corrected for non-displaceable distribution volume resulting in BPND (= k3 / k4) images for illustration purposes. (A) T1-weighted MRI and parametric images [18F]DPA-714 binding in the brains of two long COVID patients. High binding capacity (BPND) values ​​indicate more tracer binding and thus higher levels of neuroinflammation. Long COVID patients 1 showed significantly higher binding in all brain regions than in healthy control subjects. Long COVID Patient 2 also showed higher binding, with higher BPND values ​​than healthy control subjects. (B) T1-weighted MRI and parametric images [18F]DPA-714 binding to the brain of three healthy control subjects.

Study findings

According to neuropsychological test scores, both long-term COVID patients experienced fatigue, severe functional impairment, and concentration problems. The first patient had mildly impaired continuous attention and verbal memory deficits, while the second had impaired attention and visual-constructive deficits.

Compared to a [¹⁸F]Both healthy control subjects and MS patients’ DPA-714 cohort, tracer parent fraction, and total blood activity concentration were within the correct range for the study patients. Therefore, differences in tracer metabolism could not properly explain any of the differences [¹⁸F]DPA-714 binding.

MRI of healthy control subjects and the first long COVID patient was age-appropriate; However, MRI of the second patient had mild atrophy in the parietal region. In addition, the first patient is shown to be severely high [¹⁸F]DPA-714 binding to all brain regions. Compared to healthy control, BP_ND (= k3 / k4) Values ​​obtained from 2T4k_V_B The model for the first patient increased by an average of 121%, while the same values ​​for the second patient increased by an average of 79%.

Conclusion

The study has shown a wide increase in data [¹⁸F]DPA-714 binding across the brain in two long COVID patients. The scope and magnitude of the study observations may not be definite but were significant; Therefore, further research is needed to understand whether anti-inflammatory treatment may be beneficial for long-term covid patients.

* Important information

medRxiv Publishes preliminary scientific reports that have not been peer-reviewed and, therefore, should not be treated as conclusive, medical practice / health-related behavioral guidance, or established information.