signs of covid-19 symptoms

A multi-institutional research team from France studied the immunological response in patients of varying severity and found a characteristic pattern of immune response in covid-19 cases.

Signs of covid-19 symptoms With the COVID-19 pandemic showing no signs of diminishing in some parts of the world, a better understanding of the different effects on people is crucial in the individual treatment of patients.

The study included 50 patients with COVID-19 and 18 healthy participants and was published in the July issue of Science. The COVID-19 cases varied in severity of the disease from those with mild symptoms of COVID-19 to severe symptoms. They were divided into mild to moderate, seriously ill, and seriously ill cases.

The team found that the type 1 interferon response was greatly reduced in critically ill patients with COVID-19. In addition, they also observed high viral loads in the seriously ill and critically ill groups of patients, indicating poor control of virus growth in these patients. This uncontrolled virus growth in turn triggers the inflammatory reaction, which is characterized by the increased levels of the proteins TNF-alpha and IL-6 observed in the more severe cases.

Interferons are proteins that are released by cells when they detect a pathogen such as a virus. The binding of interferons to their specific receptors, which are present on many types of immune cells, activates a sequence of events that lead to both pro-inflammatory and anti-inflammatory responses. Of the three types of interferons in humans, types I and II cause an inflammatory response in immune cells, which then either kill the infected cells or use antibodies to clear the virus. Type III interferons do not have an inflammatory reaction, but reduce virus replication. A strong interferon reaction correlates with milder infection symptoms.

Changes in type I interferon response associated with worsening clinical signs of covid-19 symptoms

While severe cases of COVID-19 can appear early in some cases, most severe cases show two-stage disease progression. In the first stage, the patient will have mild or moderate symptoms, followed by worsening of symptoms, particularly respiratory problems, about 9 to 12 days after the first symptoms.

To better understand the immunological response at the level of gene activity, the French research team quantified the expression of immune-related genes in white blood cells, which are present in the blood of patients with varying degrees of disease severity. They found an increase in the activation of genes involved in both type I and type II interferon responses; This increase was higher in the easy to moderate group than in the most difficult group.

The genes that are normally stimulated by type I interferon showed a significant reduction in expression in critically ill patients compared to patients with mild symptoms. Interferon activity was also reduced in critically ill patients. Importantly, the low type I interferon response preceded the worsening of clinical respiratory symptoms in patients, which was characterized by the need for mechanical ventilation.

Differences in the viral load in the blood of patients with different severity of signs of covid-19 symptoms

Using an ultra-sensitive PCR method, the researchers found an increased viral load in the plasma of severe and critically ill patients compared to the mild to moderate group; This difference was observed even though the viral load in nasal swabs detected by classic RT-PCR methods showed no differences between the patient groups.

Increased inflammatory response in more severe cases

Cytokines are small proteins that act as signaling molecules in the immune system. Of these, interleukins are cytokines that are produced by T cells as part of the body’s inflammatory response. This study found high levels of the IL-6 protein, a type of interleukin, in the blood of critically and critically ill patient groups. The researchers also found evidence of activation of the IL-6 signaling pathway, which is involved in the inflammatory response. The transcription factor NF-kB-dependent pathways were also specifically activated in the severely and critically ill groups of patients. These results suggest an excessive inflammatory response in patients as the severity of COVID-19 disease increases.

The low-level type I interferon responses observed in SARS-CoV2 infections differ from the responses triggered by other respiratory viruses such as influenza A virus or human respiratory syncytial virus, which are associated with a high type I interferon response. The results presented in this study suggest that “SARS-CoV2 has developed efficient mechanisms to stop the host’s IFN (interferon) production.”

The researchers suggest that the type I interferon deficiency could serve as a signature for more severe forms of COVID-19 and help identify the population at risk. In addition, careful administration of interferon in more severe cases in combination with anti-inflammatory drugs against certain molecules that are elevated in critically ill patients could be a therapeutic avenue to be evaluated in future studies.

Written by Bhavana Achary, Ph.D.

References:

Original study: Hadjadj J., Yatim N., Barnabei L. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients (published online before going to press, July 13, 2020). Science. 2020

Press release: https://www.eurekalert.org/pub_releases/2020-07/ind-t1i071720.php

Additional reading: https://medium.com/swlh/interferon-responses-could-explain-susceptibility-to-severe-covid-19-cc69a654b999

Image by PIRO4D from Pixabay

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