swiss medicaThe death toll from COVID-2019 caused by the new SARS-CoV-2 coronavirus has already exceeded seven thousand people worldwide. All these people usually died from symptoms of pneumonia. It is an acute respiratory disease that has been known for almost two centuries.
What kinds of pneumonia are there?
Bacterial pneumonia was scientifically described in the XIX century and the first known pathogens (pneumococci) had been identified about the same time. Such pneumonia is also called “typical pneumonia”, infection in the lower respiratory tract provokes inflammation and accumulation of fluid in the alveoli, exudate is produced and respiratory failure occurs.
In the middle of the twentieth-century atypical pneumonia was also described which can be provoked by many pathogens like Chlamydia, Mycoplasma, Legionella, and Viruses. It does not have classic clinical features and may not be accompanied by high temperature, wheezing, sputum with blood. General signs of intoxication and dry cough may dominate during its course. As a rule, only an indistinct infiltrate can be observed on the x-ray images.
There is a discussion among doctors which continues to this day about whether the virus can cause pneumonia. The classic mechanism of pneumonia is associated with certain properties of bacteria, the substances they emit and the immune response that bacterial agents induce. On this background viruses either do not cause pneumonia at all or if they do then it is an atypical one.
Atypical pneumonia can be called interstitial because the fluid does not appear in the alveoli but in the interstitial tissue (the connective tissue between alveoli). This contributes to the formation of non-specific changes when “all is well” in the alveoli. The inflammation can only be seen with the help of a CT scan. There you can see the so-called “ground-glass opacity” (GGO) or some other interstitial markings.
Department of Radiology, University of Michigan Health System
SARS outbreak (severe acute respiratory syndrome) in the early 2000s followed by the H1N1 flu pandemic in 2009-2010 caused many deaths. People died from viral pneumonia and in some cases because of acute respiratory distress syndrome (ARDS).
What is this syndrome?
ARDS is a non-specific lung injury that can develop in response to various stimuli such as infection, injury or the inhalation of poison gas (e.g. chlorine used in the First World War).
To explain its effects we need to talk about the structure of the lungs. This is a system that transfers oxygen from the air into the blood. It is necessary to get oxygen into the fluid and at the same time not to allow the liquid to fill the alveoli with fluid. For this reason, the lungs have special structures such as endothelium and alveolar-capillary membrane which prevent the fluid from entering the alveoli.
Once ARDS develops, these structures begin to collapse, cease to hold back the liquid and it immediately fills the alveoli along the pressure gradient. The so-called noncardiogenic pulmonary edema is formed.
Acute respiratory distress syndrome (ARDS)
ARDS is a type of respiratory failure characterized by the rapid onset of widespread inflammation in the lungs. This condition can be the result of pulmonary pathology and many life-threatening conditions.
Direct damaging effects on the lungs can be in pneumonia and lung injuries. Such conditions violate the integrity of the epithelium in the bronchi and alveoli. It leads to the blockage of the bronchi, partial collapse of the lungs, the development of pulmonary edema (alveolar and interstitial).
Severe infections (sepsis, peritonitis), acute pancreatitis, severe injuries, and massive blood transfusions are the most common conditions when the lungs are affected indirectly. They damage pulmonary capillary endothelium which causes the release of plasma and blood cells in the interstitium. As a result, the interalveolar septum becomes thicker and gas exchange becomes more difficult. In the future, severe microcirculation disturbance in the lungs develops and the fluid goes to the alveoli.
The symptoms of ARDS include shortness of breath, wheezing, cyanosis, tachycardia, arterial hypertension and later anxiety and excitement can be observed.
ARDS develops within a few hours or days after the effect of the damaging factor. It is usually accompanied by multiple organ failure (MOF).
Virus plays a role in the direct damaging effect. It seems to multiply in the alveolar epithelium and the infected cells cease to perform their function. In addition, the cells turn on apoptosis (programmed cell death), they can be destroyed by macrophages.
The body’s immune response also plays a very important role. The virus doesn’t just multiply in the cells it leaves its own antigen on the cell surface. Due to the new antigen, the cells of the immune system recognize the damaged cells. Massive cellular damage by the virus is also important here as well as perhaps the absence of any other targeted immune mechanisms. When the targeted immunity fails then “heavy artillery” is activated which helps the virus destroy the lungs.
It does not mean that if we “turn off” the immune system of the patient he will be well and it does not imply that people with immunodeficiency will not suffer from such severe viral pneumonia. In general, the mechanism is mainly related to the immune response.
It can happen in the cases of sepsis and septic shock as well not only in pneumonia. The severity of the condition can be affected by both bacterial infection of the blood and the immune response of our body.
We explain step by step: bacteria enter the respiratory system and begin to multiply there. What’s next
Bacteria reach the lungs and continue to multiply there. There are so-called alveolar macrophages inside the alveoli in the lungs. They get/ phagocytose the bacterium, kill it and expose its antigens to other immune cells which begin to study them while simultaneously producing a mass of mediators that attract other cells.
Other macrophages arrive at the focus of inflammation, neutrophils come there. They are already an “atomic weapon” of the immune system that could completely destroy everything. T cells and B cells are also known as T lymphocytes B lymphocytes migrate to the focus of inflammation. B cells produce immunoglobulins which bind to bacterial antigens. It helps attract other immune cells to attack. The role of T cells is slightly less here; they are able to destroy bacteria directly.
When bacteria are destroyed toxic substances are released and it leads to an increase in temperature. The arachidonic acid is activated, prostaglandins are produced so it increases blood flow to the site of inflammation and the speed of biochemical reactions increases. Further, if the body is strong it destroys infection itself and infectious disease is not allowed to spread.
If the body is not strong the bacteria can multiply and move to other organs. Sepsis can develop: this is a condition in which bacteria reach the bloodstream. A massive release of some bacterial toxins can lead to the development of a systemic reaction like hypotension, shock.
This is a pathogenic mechanism of typical pneumonia triggered by a bacterial infection. But the mechanism in the case of viruses is about the same. However in comparison with the bacterium virus is more generalized, it affects many tissues and viruses are more difficult to fight with they do not have a cell wall that can be destroyed.
The virus constantly infects new cells and then these cells become the source of a new virus. Therefore several other immune mechanisms work here just T-cells, macrophages, and antibodies.
Is it true that the lungs cease to oxygenate the blood and the person dies from suffocation with severe pneumonia?
In the case of bacterial pneumonia the structures are destroyed, the alveoli are filled with an infiltrate containing the cell debris, bacteria, and cells of the immune system. In fact the lung turns into a sponge filled with liquid. The greater part of the lung is occupied by the infiltrate, the worse the person breathes. At some point critical respiratory failure occurs.
This may be accompanied by heart disorders, cerebral edema can develop. But a decrease of blood oxygen level is inevitable, and it can fall to a level incompatible with life.
Can antibiotics stop this process?
Yes, antibiotics destroy all bacteria. The immune system will just have to clean up these dead fields with macrophages and the patient will have to wait until the lungs are clean.
But antibiotics do not give a 100% guarantee against ARDS. A large number of bacteria can be destroyed with intensive antibiotic treatment which leads to the release of a huge number of toxins into the blood.
How does it work in the case of viruses when there are no foreign cells?
There are cells infected with the virus. Each virus exposes its antigens to the surface of the cell and it becomes a target for our immune system. The immune system fights this cell and destroys it.
It happens that a virus has infected many cells in the lungs but at first the immune system didn’t work the way it should. Then the body can overreact in response to massive infection and destroy too many cells. ARDS can also develop because of such “atomic war” at the level of immunity.
We wrote earlier about a cytokine storm of the immune system and why transplantation of mesenchymal stem cells can stop this reaction, which means that it is very likely to be effectively supportive and symptomatic therapy with COVID-2019.
It is not completely clear why ARDS occurs more frequently with some viruses than others. The “old” SARS virus, bird flu virus and new coronavirus can even cause such a reaction to a greater extent.
The lungs consist of air “sacs” called alveoli and interstitium which is located between the groups of these sacs. This can be compared with bunches of grapes as if each one is packed in a separate bag. If you cut the tangerine then you will find large partitions between the lobules. This is the same between the alveoli and this interstitial space.
The infiltrate can fill the alveoli in bacterial pneumonia and it enters the interstitial space in viral pneumonia. So it can cause serious respiratory failure. At the same time nothing can be seen on the X-ray images and there will be some slight changes on the CT. Common clinical manifestations of coronavirus pneumonia include severe shortness of breath, signs of respiratory failure and slight changes in computed tomography.
Is there any way to stop sliding into pneumonia in the early stages? In the case of a bacterial infection you can drink antibiotics. What about the case of the virus?
Is there any way to stop sliding into pneumonia in the early stages? In the case of a bacterial infection you can drink antibiotics. What about the case of the virus?This is a different case. There are no proven methods for the prevention of pneumonia or drugs for specific antiviral therapy and we can not recommend anything yet.
The Chinese have described the use of chloroquine (an antimalarial drug). They claim it has an antiviral effect. But this data needs to be investigated. Antibiotics are worth prescribing for prevention because there is a risk of secondary bacterial infection. But apparently it does not play a big role.
Hormones do not seem to work. Antiviral drugs are likely not to work although different options have been tried with both anti-influenza and anti-HIV drugs.
While preparing this article, we examined information on the following drugs that can increase the effectiveness of SARS-CoV-2 treatment:
- Lopinavir-ritonavir (tradename KALETRA)
- Interferon alfa
- Ribavirin
- Interferon
- Chloroquine Phosphate (Chloroquine)
- Arbidol
- Remdesivir
- Umifenovir
- Arbidol Hydrochloride
- Vitamin C
There is no convincing data on the effectiveness of these drugs while. But it does not mean that they are not effective. It takes time to research, to identify risks, etc.
News that vaccines have already been found should not be misleading you. It will take months to test. We do not think that the vaccine will appear earlier than the end of the year.
What happens in an emergency situation when the lungs stop functioning? You can turn on the ventilator but it is necessary that the lungs absorb oxygen themselves. And what to do if they are filled with liquid?
Patients have many different methods to fight hypoxemia: it is possible manually to inflate lungs even to reopen sticky alveoli. All these methods work for a while. Perhaps one of the best methods for today is ECMO (extracorporeal membrane oxygenation).
We create a special membrane and the blood passes through it. The membrane allows us to oxygenate the blood. It is a similar mechanism of oxygenation when the blood passes through the lungs. As if we create artificial lungs such gills. This can save a person but in some cases it doesn’t work.
In general it is important to understand: when the patient’s condition is so critical that ECMO is required. As a rule it occurs with other organs involvement. Multisystemic failure develops. We save the lungs but kidneys fail. We save kidneys but brain swelling begins.
Can the lungs be restored, can a person return after ECMO?
We have mesenchymal stem cells capable of regenerating the lungs in varying degrees. We should take into consideration that new lungs cannot be grown again but the epithelium can be renewed and the membrane can be restored.
At the moment about 5% of patients are suggested to have pulmonary fibrosis as a complication.
Pulmonary fibrosis (PF) is a pathology characterized by the replacement of the organ’s own tissues with connective tissue. The functioning of the lung structural units of the lung is impaired which leads to respiratory failure. The condition occurs as a reaction of the body to inflammatory processes and it isolates the foci of inflammation with scar tissue.
PF is a serious disease that does not respond well to treatment.
We will talk about a protocol for treating pulmonary fibrosis with mesenchymal stem cells in the next article. Subscribe to our newsletter.
There are several ARDS scenarios. If it is favorable one the cells begin to regenerate. But in case of an unfavorable scenario the basement membrane dies and fibrosis begins instead of regeneration. So connective tissue grows instead of cells. This is not fatal but lung function is impaired due to the fact that the architecture of the alveoli and the pulmonary lobe is lost in PF.
Is it still possible to recover after being on a ventilator?
It is still possible. At least 50% of the patients survive according to statistics. The mortality rate can be not higher than 20-25% with the super examination, super-elaborated protocols.
How long can a person be on a ventilator?
This period is unlimited if there is no lung damage. So the person can live his whole life on a ventilator. But regeneration usually takes place around a month.
Yes. But the scenarios of cases among patients with new coronavirus infection are as follows: 80% of patients have it in a mild form, 15% of them suffer moderate to severe symptoms. As a rule in both situations mechanical ventilation is not required. Due to the most severe cases the mortality rate is growing up. This is 5% of patients.
