COVID-19 Publication: Uncovering Cytokines Driving Neuroinflammation in COVID-19 Patients with IsoPlexis’ Unique Functional Proteomics

IsoPlexis’ Unique Low Sample Volume Functional Proteomics Identifies Key Inflammatory Signatures in CSF of COVID-19 Patient in Case Study

While COVID-19/SARS-CoV-2 and similar coronaviruses in humans are considered to be respiratory pathogens, a subset of patients with COVID-19 have presented with extrapulmonary disease along with neurological complications. A recent article, published in BMC Neurology titled “Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19” focuses on a case where an immunocompromised patient “presented with altered mental status after witnessed  seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation.”1

The patient arrived at an academic medical center with the above symptoms as well as: “sudden-onset of uncontrolled limb movements with ocular deviation followed by several minutes of unresponsiveness. At her baseline, the patient lived independently and had no previous diagnosis of dementia or confusion. However, three days prior to admission, she was noted to have confusion and disorientation.”1

Following four days of hospitalization, the patient was tested for SARS-CoV-2 and was positive for COVID-19.

CSF Data

IsoPlexis’ CodePlex Technology Allows for Unique Highly Multiplexed Functional Analysis of Plasma and CSF With 5 Mins of Hands-On Time

Researchers Farhadian, et al. utilized IsoPlexis’ CodePlex technology to analyze both cerebrospinal fluid (CSF) and plasma from the patient, against three healthy controls. The CodePlex highly multiplexed cytokine assay found that the “levels of IL-6, IL-8, and IP-10 appeared to be elevated in both CSF and plasma of this patient compared to control, with a unique MCP-1 signature found only in CSF and not plasma.”1

MCP-1 (monocyte chemoattractive protein-1), also known as CCL2 is one of the chemokines/cytokines that plays a role in regulating the migration or infiltration of monocytes and macrophages. CCL2 recruits all sorts of immune cells to sites of inflammation in the body. However, when the patient’s CSF was tested for SARS-CoV-2, the first attempt via qRT-PCR was negative, the second used targeted sequencing and identified a total of 60 reads aligning with SARS-CoV-2, but that was not above background. The final attempt by PCR did not detect any SARS-CoV-2.1 Notably, MCP-1/CCL2 was only present in CSF and not plasma, when the COVID-19 virus was found in the blood and not CSF of this patient.

IsoPlexis’ Predictive Functional Proteomics Identifies Unique Signatures from CSF and Indications of Neuroinflammation, Despite the Absence of Viral Presence in the CSF

Several recently-conducted studies have found evidence of similar neurological instances in subsets of COVID-19 patients. A Wuhan, China study found that 36.4% of COVID-19 patients exhibited peripheral nervous system, skeletal muscle, or central CNS symptoms.1 A study in France reported a similarly high rate of neurological symptoms in COVID-19 patients. “Twenty-six of 40 patients were noted to have confusion. Similarly to the patient in this report, that case series found no evidence for SARS-CoV-2 neuroinvasion by PCR of CSF, and EEG findings were non-specific.”1 It is still unclear, however, if the injury to the central nervous system (CNS) that is observed in COVID-19 is caused by viral invasion or by the inflammatory cytokines produced by the immune cells in the CNS.1

While patients with SARS-CoV-1 have had the virus present in the brain, MERS, another similar disease, did not have presence of the disease in CSF. And, so far, there has been only one reported instance of SARS-CoV-2 being detected in CSF.1 With the patient in this published case, the CSF also did not test positive for the virus, but there was increased inflammation, which supports the possibility that the “neurological symptoms in COVID-19 may be due to increased neuroinflammation rather than to CNS invasion of [the] virus, and that treatment of neurological complications of COVID-19 may require targeting host-inflammation. Specifically, CSF elevation of MCP-1 as well as emerging reports of macrophage induced damage in lung and other tissues suggests that specifically attenuating monocyte-incurred damage may prove beneficial.”1

Cellular and cytokine level monitoring is essential for predicting toxicities in infectious diseases, such as those related to cytokine storm seen in many COVID-19 patients. Predicting which patients are likely to experience cytokine storm can help researchers formulate better therapeutics and potentially prevent the response from occurring. IsoPlexis’ CodePlex solution is helping to provide highly multiplexed cytokine data in an automated manner that doesn’t require advanced training.

Read the full BMC Neurology publication here and click here to learn more about the Cytokine Storm Package IsoPlexis is offering to help researchers accelerate the development of COVID-19 vaccines and therapeutics.

Reference:

  1. Farhadian S, et al. Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19. BMC Neurology 20: 284, 2020.
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