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May 11, 2020 10:11

Patient Immune Battle Against COVID-19

Immune complications after SARS-CoV-2 infection

My stepfather entered the corridor, troubled. The man is usually someone who doesn't make a big show of how he feels. He uses to pass by our house at least two times a week to barter and discuss a little. I buy fresh eggs from my neighbor and trade them against fresh vegetables my stepfather grows.

But that morning, Luc wasn't on his game. Looking the other way, he wasn't outlining the slightest smile. He leaned gently toward me and whispered a few words.

His mother just passed away. It all happened suddenly.  In the space of just a few days.

Chronicle of a death foretold.

 

1. Primary battle zone: From fever to lung infection

It starts with a fever for 94% of us on the first day. We feel exhausted in some cases (23%), and face muscle pain (15%) like the day after a big workout. And we start coughing after 5 days. A lot, in fact (79% of reported cases)(1).

At this point, severe cases (15%, according to the Chinese CDC) start experiencing polypnea; an increase in the number of breathing cycles per minute, and a decrease in the amplitude of breathing movements. In short, you are progressively running out of air.

Doctors are accustomed to polypnea (firstly described in 1889) and know to search the causes in lung or heart diseases. At the beginning of the pandemia, polypnea was the first symptom observed to attest to infection aggravation. In 2020 January 7th, it allows scientists to publish the first X-ray images and sample bronchoalveolar-lavage fluids to finally isolate and sequence viral RNA. This coronavirus was not like the others. Scientists just stumbled upon the newest member of the coronavirus family, the 7th one (2): COVID-19.

And curiously enough, they started observing something else occurring in patients.

 

2. Multiple battlefields: Beyond the lung infection

By mid-January 2020, in Wuhan hospital, the dialysis machines began to run out.

In the emergency rooms treating COVID-19, renal distress was raging : 23 patients over a total of 85 exhibited acute renal failure (3).

In February, another hospital reported heart-related complications: 23% of the patients were suffering arrhythmia, and 10% of them faced acute cardiac injury (4).

Lung. Kidney. Heart. Where does the list end?

These abnormalities have chained themselves to finally reached the neurological system. Acute cerebrovascular events spread among severe infected patients (36% of a total of 214 patients). Loss of smell, headaches, ataxia, and nerve pains were proliferating (5).

But this time, scientific community had a suspect.

A familiar suspect we have already encountered in many virus investigations.

 

3. Your immune system is fighting you

Cytokine Release Syndrome (CRS) has just made its appearance at the top of the suspect list.

Knowing where to look, scientists started to search for some clues. Tracking elevated concentrations of inflammatory cytokines and chemokines, they found that IL-6, IL-2, IL-1β, IL-8, IL-17 ,IFN-γ, TNF-α, IP10, MCP-1, IL-10, IL-4 were all on board in COVID-19 patients. No doubt, CRS was involved (6).

This disproportionate immune response from the host becomes unfavorable, deleterious, and lead to the failure of several vital organs and death.

But something even more surprising was recently revealed at the end of April.

During any viral infection, our immune response produces the first class of interferon, IFNa. This cytokine has the potential to protect patients and has consequently been used to treat hepatitis B and C.

In the particular case of COVID-19, scientists found that interferon-alpha induces ACE2 gene expression. Since ACE2 is the receptor of the virus on cells, it means that your immune system creates new entries for the virus to get into cells.

The more your immune system responds to the threat, the more it helps the virus to destroy you.

 

If lungs were the first organs targeted by COVID-19, due to the high expression of ACE2 on the surface of epithelial cells, it appears that the viral infection triggers Cytokine Release Syndrome.

This overdrive immune reaction leads inexorably to the fall, one after the other, of all the patient organs.

Worse than that and thanks to the overexpression of the ACE2 gene, cytokine IFNa seems to offer more cell portals to virus, so accelerating the processus of certain death.

The best trick of the virus remains to turn our immune system against us.

 

REFERENCES

(1) A retrospective study on the first 191 patients in Wuhan, China. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study – Fei Zhou, Ting Yu, Ronghui Du.

(2) A Novel Coronavirus from Patients with Pneumonia in China, 2019 - Na Zhu, Ph.D., Dingyu Zhang, M.D., Wenling Wang, Ph.D., Xingwang Li, M.D., Bo Yang, M.S., Jingdong Song, Ph.D., Xiang Zhao, Ph.D., Baoying Huang, Ph.D., Weifeng Shi, Ph.D., Roujian Lu, M.D., Peihua Niu, Ph.D., Faxian Zhan, Ph.D., et al.

(3) Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection – Bo Diao, Chenhui Wang, Rongshuai Wang, Zeqing Feng, Yingjun Tan, Huiming Wang, Changsong Wang, Liang Liu

(4) Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China - Dawei Wang, MD; Bo Hu, MD; Chang Hu, MD; et al

(5) Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China- Ling Mao; Huijuan Jin; Mengdie Wang; et al

(6) Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? - Bingwen LiuMin LiZhiguang ZhouXuan Guan, and Yufei Xiang

(7) SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues - Carly G.K. Ziegler, Samuel J. Allon, Sarah K. Nyquist, Alex K. Shalek, Jose Ordovas-Montanes

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