Coronaviruses are a type of virus widely present in nature, named for their crown-like appearance under an electron microscope. So far, coronaviruses have been found to infect only vertebrates and can cause respiratory, digestive, and nervous system diseases in humans and animals.

The 2019 novel coronavirus (2019-nCoV) is the seventh known coronavirus that can infect humans. The other six are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, and MERS-CoV.

The 2019 novel coronavirus (2019-nCoV) was discovered due to cases of viral pneumonia in Wuhan in 2019 and was named by the World Health Organization on January 12, 2020. On February 12, 2020, the International Committee on Taxonomy of Viruses (ICTV) announced that the official classification name of the novel coronavirus (2019-nCoV) is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On the same day, the World Health Organization (WHO) announced that the official name of the disease caused by this virus is COVID-19.

The 2019 novel coronavirus (2019-nCoV) belongs to the beta genus of coronaviruses. It is enveloped, with particles that are round or oval, often pleomorphic, and 60-140 nm in diameter. The virus is sensitive to ultraviolet light and heat; it can be effectively inactivated by 56°C for 30 minutes, ether, 75% ethanol, chlorine-containing disinfectants, peracetic acid, and chloroform. Chlorhexidine cannot effectively inactivate the virus.

On January 24, The Lancet published two research papers on the novel coronavirus online, mentioning that among the first confirmed severe 2019-nCoV infections, many patients experienced a "cytokine storm."

Previous cases of SARS, Middle East respiratory syndrome, and Ebola virus infections have proven that cytokine storms are the real killers, triggering the immune system to launch a fierce attack on the body.

A cytokine storm refers to the rapid and massive production of various cytokines such as TNF-α, IL-1, IL-6, IL-12, IFN-γ, MCP-1, and IL-8 in body fluids after microbial infection. It is a major cause of acute respiratory distress syndrome and multiple organ failure.

Research shows that the novel coronavirus enters cells through angiotensin-converting enzyme 2 (ACE2), so lung tissue with high ACE2 expression and easy viral entry becomes the main target of the novel coronavirus.

After the virus enters the lungs, the immune system sends a large number of immune cells to the lung tissue to fight the virus, resulting in pneumonia. Patients exhibit fever, cough, and difficulty breathing. However, these immune cells are not powerful enough to accurately eliminate the virus and can only indiscriminately bombard, recruiting more immune cells to fight, leading to an accumulation of immune cells and cytokines.

Once a cytokine storm forms, the immune system may not kill the virus but will definitely kill a large number of normal lung cells, severely damaging lung ventilation function. This appears as large white areas on lung CT scans, known as "white lung." Patients may suffer respiratory failure and die from hypoxia.

Besides the lungs, ACE2 is also highly expressed in vascular endothelial cells, heart, kidneys, liver, digestive tract, and other organs. All tissues and organs expressing ACE2 may become battlefields between the novel coronavirus and immune cells, leading to multiple organ failure.

As mentioned earlier, the novel coronavirus can trigger the immune system to launch a fierce attack on the body, causing acute respiratory distress syndrome and multiple organ failure. Currently, there is no effective treatment. Stem cells often have miraculous effects on difficult and severe diseases that other treatments cannot handle. So how will stem cells play a role in treating severe COVID-19 this time?

Previous clinical studies have already demonstrated that stem cells play a significant role in treating inflammation across multiple tissues and organs, including conditions such as lupus nephritis, severe hepatitis, osteoarthritis, and rheumatoid arthritis. Among the diverse stem cell types, mesenchymal stem cells (MSCs) stand out due to their low immunogenicity, ability to secrete growth factors, modulate immune responses and inflammation, and combat oxidative stress. Moreover, MSCs directly contribute to tissue repair and show remarkable therapeutic potential for a wide range of inflammation-related diseases.

Therefore, similar to its role in combating H5N1 and H9N2 influenza viruses, mesenchymal stem cells (MSCs) can also improve the lung environment and alleviate symptoms in critically ill patients with novel coronavirus pneumonia by mechanisms such as reducing inflammatory responses, minimizing inflammatory exudates, and enhancing the survival rate of alveolar capillary endothelial cells. However, since an inflammatory milieu can also impair the therapeutic efficacy of MSCs, it is crucial not to rely solely on MSCs for treatment during severe stages of pneumonia—but rather to adopt a comprehensive therapeutic approach instead.

Figure 4: Plasticity of MSCs in immune regulation [10]

Figure 8: Intravenous injection of itMSC can reduce neutrophils in the heart [13]

As previously discussed, the "cytokine storm"—an overreaction of the body's immune system triggered by viral infection in an attempt to eliminate the virus—is the real life-threatening culprit. Administering MSCs at the right therapeutic window, followed by intravenous infusion, allows these cells to initially migrate to the lungs, where they help modulate inflammation, prevent excessive immune responses, reduce tissue damage, and even promote the repair of injured areas. This approach is expected to play a positive role in treating critically ill patients. Therefore, itMSCs—possessing enhanced anti-inflammatory capabilities—may be particularly well-suited for addressing viral pneumonia. Moving forward, Jiuzhitang Maker plans to collaborate more actively with leading domestic medical institutions to conduct additional, clinically relevant studies in this area.