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Patients’ Immune Battle Against COVID-19

 

My stepfather entered the hallway, he seemed troubled by something. He isn’t the kind of man who usually shows his feelings. He used to pass by our house at least twice a week to discuss a while and to barter. I buy fresh eggs from my neighbour and trade them against fresh vegetables my stepfather grows.

  

But that morning, Luc wasn’t himself. His gaze averted, not the slightest of smile on his lips. He leaned gently towards me and whispered a few words.

 

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

 

 

A brief review of the expected complications.

 

1. Primary battle zone: From fever to lung infection

 

On the first day it starts with a fever for 94% of us. We feel exhausted in some cases (23%), and face muscle pain like the day after a big workout (15%). 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 (first described in 1889) and know to search the causes in lung or heart diseases. At the beginning of the pandemic, polypnea was the first symptom observed to attest worsening infection. On January 7th 2020, Chinese scientists released 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 that was occurring in patients.

 

2. Multiple battlefields: Beyond the lung infection

 

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

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

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

 

 

Lungs. Kidneys. Heart. Where does the list end?

 

 

These abnormalities followed on from one another to finally reach the neurological system. Acute cerebrovascular events spread among severely infected patients (36% of a total of 214 patients). Loss of smell, headaches, ataxia and nerve pains were proliferating (5).

 

But this time, the scientific community had a suspect.

 

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

 

3. Your immune system is fighting against you

 

 

 

 

 

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

 

 

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 and IL-4 were all present in COVID-19 patients. There was no doubt, CRS was involved (6).

 

 

This disproportionate immune response from the host becomes unfavourable, deleterious, and leads 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 type 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 may induce ACE2 gene expression. Since ACE2 is the receptor of the virus on cells, it would mean that your immune system creates new entries for the virus to get into cells. This discovery is still awaiting confirmation.

 

 

More your immune system responds to the threat, 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 immune reaction overdrive leads inexorably to the fall, one after the other, of all the patients’ organs.

 

 

Worse than that and due to the overexpression of the ACE2 gene, the cytokine IFNa seems to offer more cell portals to the virus, so accelerating the process of a highly probable death.

 

 

The best trick of the virus is being able to turn our proper immune system against us.

 

 

 

 

 

 

REFERENCES

 

(1) 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 Liu, Min Li, Zhiguang Zhou, Xuan 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