Persistence of SARS-CoV-2 in an organization leads to long COVID

Immediately after its emergence at the end of 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a wave of catastrophic infections, hospitalizations and deaths worldwide. SARS-CoV-2 infection causes coronavirus disease 2019 (COVID-19). It is associated with a wide range of clinical features and unpredictable prognosis.

recently iScience In a pre-certified study of the journal, the authors provide evidence that severe and persistent COVID-19 may share common underlying immunological features. These findings may help identify patients at high risk for long-term illness.

study: Immune response to SARS-Cov-2 in severe disease and long-term COVID-19. Image Credits: Alexey Boldin / Shutterstock.com

Preface

After binding to the angiotensin converting enzyme 2 (ACE2) receptor, SARS-CoV-2 infects multiple cell types and invades cells. ACE2 receptors are found on the surface of human airway cells, endothelial cells of the cerebrovascular system, smooth muscle cells of the vessel wall, and several types of cells in the gastrointestinal tract.

A significant amount of research has focused on characterizing SARS-CoV-2 infections and immune responses. For example, modeling studies may help predict the characteristics of COVID-19 that are exacerbated by disturbing the immune environment or that cause the acute sequelae of COVID-19 (PASC) or a chronic disease known as long Covid. I have.

For example, some models mimic the spread of SARS-CoV-2 and the subsequent immune response in the lungs. Others simulated the invasion of SARS-CoV-2 and its replication in epithelial cells, followed by its spread through the circulation, resulting in systemic inflammation and abnormal coagulation.

In the current study, researchers are investigating how SARS-CoV-2 affects immune cells, cytokines, and other related molecules within the network of interactions. The authors also discuss the effects of age-related factors on the severity of COVID-19.

Infecting IFN1 and DC

Type 1 interferon (IFN1) is a powerful, early cytokine released by virus-infected cells.

Dendritic cells (DCs) are primary immune cells that contribute to innate immunity. DC cells also lose function with age, as evidenced by their reduced ability to migrate and phagocytose. Nevertheless, DC remains abundant and has the same phenotype.

When DC encounters a viral antigen in the early stages of infection, it transforms into antigen-presenting cells (APCs). Therefore, DC levels rise rapidly after symptoms appear. APC migrates to local lymph nodes and proliferates, while at the same time inducing naive CD4 T cells to differentiate into type 1 T helper cells (Th1) and T follicular helper cells (Tfh).

Previous studies have shown a sustained decrease in CD1c + DC from COVID-19 resolution up to 7 months, regardless of the initial severity of the disease.

Lymph node APC and Tfh induce the differentiation and proliferation of naive B cells into antibody-producing B cells. These cells also promote the differentiation of naive CD8 T cells into cytotoxic T lymphocytes (CTLs) that migrate to the site of infection. CTLs kill infected cells and cause the count to drop sharply, but some of the newly generated virions within the infected cells break down at a much slower rate.

Survey results

The model used in the current study is that low APC activity with impaired IFN1 response, Viral load It peaked 2 hours after infection. This was accompanied by higher persistent viral load due to the increase in infected cells.

IFN1 signaling has a profound effect on the suppression of viral replication in infected cells.. “

The viral load decreased following the initial increase. After reaching the lowest point, a slow rise to equilibrium occurred. The model also reported that IFN1 production was dysregulated by both SARS-CoV-2 and aging.

SARS-CoV-2 can avoid the antiviral response caused by IFN1. IFN1 levels are expected to decline at the same time as low APC activity, as infected cells increase at a much faster rate than APCs exposed to the antigen.

Chronic DC decline and PASC

The model also confirmed a decrease in DC over time compared to healthy donors, thus causing persistent virus persistence and associated DC-induced inflammation. A rapid decrease in DC levels was observed in acute infections, which subsequently increased below baseline. The initial decline was due to the persistence of the undetectable virus in the host.

In this model, a persistent decrease in DC during acute infection and after clinical resolution is associated with chronic inflammation manifested as PASC.

Similarly, Pediatric multisystem inflammatory syndrome (MIS-C), DC appears to decrease over time. These patients also show fewer nonclassical monocytes and a set of natural killer (NK) cells. Therefore, this response also indicates that it is involved in the ongoing inflammation previously reported in children infected with SARS-CoV-2.

Aging and COVID-19

With age, immunity is lost as well. New infections are more common and latent infections can become active, both of which tend to exacerbate the severity of the disease.

In particular, older people are very likely to develop severe COVID-19. This can be explained by the increasing presence of IFN1-.Autoantibodies It was observed in more than 1 in 5 patients aged 70 years and older and those infected with COVID-19.

Significant reductions in CTLs lead to persistent infections, and even moderate viral loads may explain delayed viral clearance. Such a decrease did not affect the initial viral load, even by an order of magnitude, as seen with aging.

In summary, the aforementioned findings suggest that all patients who are partially deficient in innate and / or adaptive immunity due to inflammation and (immune) disease may be at increased risk of severe or fatal COVID-19. Shows that there is sex.. “

An increasingly powerful antiviral response increases the chances of complete viral clearance. Persistent SARS-CoV-2 at a constant rate increases the risk of PASC.

Implications

This model suggests that even moderate SARS-CoV-2 loading is not cleared by many patients with immune disorders because the immune system is unable to block viral replication. The long-term persistence of SARS-CoV-2 has been reported in various previous studies.

Therefore, PASC is likely to be the result of long-term persistence of SARS-CoV-2 in a variety of tissues, rather than the protracted effects of viral or inflammation-induced tissue or thrombotic damage during acute disease. ..

Chronic reduction in DC is due to the presence of SARS-CoV-2 in long Covids resulting in migration to inflamed areas. This prediction is supported by the depletion of certain other innate immune cells.

In other words, the model suggests that:Successful removal of the virus depends on the ability of the host’s immune response, which is directly related to viral load... “

Future studies also need to identify the infectivity of these patients and better PASC management strategies.