**5. Correlation between covid-19, brain injury and neuroinflammation**

Vulnerable children are those with neurological diseases and lung problems, requiring respiratory care [66]. This situation is currently a priority with the advent of the new coronavirus disease of 2019 (COVID-19). This is a zoonotic virus, an enveloped RNA, which can be transmitted from a sick person to another by close contact through touch, handshake, droplets of saliva, sneeze, cough, phlegm and contaminated objects or surfaces [67, 68].

It was first detected in December 2019 and became an epidemic in Wuhan, Hubei province, China and quickly spread to several countries on six continents [69]. On March 11, 2020, the World Health Organization announced that COVID-19 was characterized as a pandemic, threatening global public health and creating a record economic burden. Coronaviruses are a large family of viruses that cause diseases such as the common cold to more serious diseases, such as Severe Acute Respiratory Syndrome (SARS). A new coronavirus is typically a new strain of infectious disease that has not been previously identified in humans [70].

The new 2019 coronavirus, coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) appeared after six other human coronaviruses. Four common human coronaviruses which cause light to moderate illness of the superior respiratory tract, including 229E (coronavirus alpha), NL63 (alpha coronavirus), OC43 (beta coronavirus) and HKU1 (beta coronavirus), were registered for the first time in the 60's [71]. Two other human coronaviruses are SARS-CoV and MERS-CoV, which cause grave infections to pulmonary lesions, known as Severe Acute Respiratory Sickness (SARS-C0V) and Middle East Respiratory Syndrome (MERS-CoV), respectively. The MERS-CoV outbreak occurred in 2012, starting in Saudi Arabia and spreading to other countries with a mortality rate of 37% [71, 72].

These are the diagnostic criteria [73]:


**51**

Treg [80].

*Brain Injury and Neuroinflammation of the Gut-Brain Axis in Subjects with Cerebral Palsy*

The majority of discussions based on evidence demonstrate the power of privilege during a pandemic, where it is indicated that the most vulnerable, such as seniors, people with deficiencies and aborigenes, will be the most impacted [74]. Children of all ages are sensitive to Covid-19, and there is no significant difference between the sexes. The clinical manifestations of cases of children with Covid-19 were less serious than those of adult patients. Nevertheless, small children, especially babies, are also vulnerable to infection by Covid-19 [75]. Many families have to live in just one room with shared bathrooms and kitchen, causing overcrowding and making self isolation impossible in confined spaces. Many times, the children have inadequate space to crawl or play, and no access to fresh air. The duration of the outbreak is not clear and these children are more vulnerable both to the primary as well as the secondary effects, it is absolutely vital that they are no

Antiviral immunity includes innate and adaptive immune responses. There are different innate immune receptors, the Toll like receptors (TLRs) are more intimately related to adaptive immune responses, therefore the TLRs are important antiviral immunity elements [77]. After a virus is recognized, the TLR signaling positively regulates the expression of pro-inflammatory cytokines and co-stimulatory molecules, through the accumulation of interferons (IFNs). Consequently, the adaptive antimicrobial immunity is processed by co-stimulatory molecules [78]. Patients with serious SARS-CoV infection show an aberration of the innate immune system. Particularly, the induction of proinflammatory cytokines, IFNs type I and genes stimulated by interferon (ISG) would suffer oscillations clearly favorable to SARS-CoV. The liberation of cytokines and pro-inflammatory chemokines occurs on the first day of infection. High levels of proinflammatory cytokines in patients with SARS-CoV are correlated to symptoms of respiratory discomfort in old animals. The IFNs can help to control the replication of SARS-CoV. Therefore, it is possible to suppose that other innate immunological mechanisms will have an

A certain subgroup of the population of T cells develops a cytokine storm during

Both winter and low humidity act as stressors for the immune system. Evidence shows an association between cold temperatures and low humidity with respiratory tract infections whereby the lower the temperature/humidity, the greater the infec-

Precocious induction of interferon-gamma (IFN-γ) in viral infections, indicates a battle between innate immunity and the virus, so the immune system would start with a fever, to allow the expression of TLR4, and would unchain a series of antiviral immune responses characterized by the production of cytokines. In almost 99%

of cases, the most common initial symptom of SARS-CoV-2 is fever [82].

Evidence points to the effect of this new coronavirus in inhibiting antiviral immune responses and, therefore, its powerful capacity to replicate in the host cells. On the other hand, SARS-CoV-2 demonstrated a greater rate of incidence of

initial stages of the SARS-CoV-2, involving cytokines and chemokines from the beginning until the other phases of the illness. In its initiation phase, SARS-CoV-2 would increase the plasma concentration of different cytokines, including IL-1β, IL-1Rα, IL-7, IL-8, IL-9, IL-10, basic FGF G CSF, GMCSF, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, TNF-α and endothelial vascular growth factor. Critical patients interned in intensive care units (ICUs) presented higher levels of IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A and TNFα compared to those who did not need to be in the ICU. In SARS-CoV-2, there appears to be an interaction between different subsets of the population of T-helper cells (Th), for example, Th1, Th2 and

*DOI: http://dx.doi.org/10.5772/intechopen.95763*

longer marginalized [76].

essential role in immunity against SARS-CoV [79].

tions in the respiratory tracts of the population [81].

#### *Brain Injury and Neuroinflammation of the Gut-Brain Axis in Subjects with Cerebral Palsy DOI: http://dx.doi.org/10.5772/intechopen.95763*

The majority of discussions based on evidence demonstrate the power of privilege during a pandemic, where it is indicated that the most vulnerable, such as seniors, people with deficiencies and aborigenes, will be the most impacted [74].

Children of all ages are sensitive to Covid-19, and there is no significant difference between the sexes. The clinical manifestations of cases of children with Covid-19 were less serious than those of adult patients. Nevertheless, small children, especially babies, are also vulnerable to infection by Covid-19 [75]. Many families have to live in just one room with shared bathrooms and kitchen, causing overcrowding and making self isolation impossible in confined spaces. Many times, the children have inadequate space to crawl or play, and no access to fresh air. The duration of the outbreak is not clear and these children are more vulnerable both to the primary as well as the secondary effects, it is absolutely vital that they are no longer marginalized [76].

Antiviral immunity includes innate and adaptive immune responses. There are different innate immune receptors, the Toll like receptors (TLRs) are more intimately related to adaptive immune responses, therefore the TLRs are important antiviral immunity elements [77]. After a virus is recognized, the TLR signaling positively regulates the expression of pro-inflammatory cytokines and co-stimulatory molecules, through the accumulation of interferons (IFNs). Consequently, the adaptive antimicrobial immunity is processed by co-stimulatory molecules [78].

Patients with serious SARS-CoV infection show an aberration of the innate immune system. Particularly, the induction of proinflammatory cytokines, IFNs type I and genes stimulated by interferon (ISG) would suffer oscillations clearly favorable to SARS-CoV. The liberation of cytokines and pro-inflammatory chemokines occurs on the first day of infection. High levels of proinflammatory cytokines in patients with SARS-CoV are correlated to symptoms of respiratory discomfort in old animals. The IFNs can help to control the replication of SARS-CoV. Therefore, it is possible to suppose that other innate immunological mechanisms will have an essential role in immunity against SARS-CoV [79].

A certain subgroup of the population of T cells develops a cytokine storm during initial stages of the SARS-CoV-2, involving cytokines and chemokines from the beginning until the other phases of the illness. In its initiation phase, SARS-CoV-2 would increase the plasma concentration of different cytokines, including IL-1β, IL-1Rα, IL-7, IL-8, IL-9, IL-10, basic FGF G CSF, GMCSF, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, TNF-α and endothelial vascular growth factor. Critical patients interned in intensive care units (ICUs) presented higher levels of IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A and TNFα compared to those who did not need to be in the ICU. In SARS-CoV-2, there appears to be an interaction between different subsets of the population of T-helper cells (Th), for example, Th1, Th2 and Treg [80].

Both winter and low humidity act as stressors for the immune system. Evidence shows an association between cold temperatures and low humidity with respiratory tract infections whereby the lower the temperature/humidity, the greater the infections in the respiratory tracts of the population [81].

Precocious induction of interferon-gamma (IFN-γ) in viral infections, indicates a battle between innate immunity and the virus, so the immune system would start with a fever, to allow the expression of TLR4, and would unchain a series of antiviral immune responses characterized by the production of cytokines. In almost 99% of cases, the most common initial symptom of SARS-CoV-2 is fever [82].

Evidence points to the effect of this new coronavirus in inhibiting antiviral immune responses and, therefore, its powerful capacity to replicate in the host cells. On the other hand, SARS-CoV-2 demonstrated a greater rate of incidence of

*Advancement and New Understanding in Brain Injury*

contaminated objects or surfaces [67, 68].

These are the diagnostic criteria [73]:

organic dysfunction can be fatal.

nausea, vomit, abdominal pain and diarrhea.

phy of the thorax shows subclinical pulmonary lesions.

**5. Correlation between covid-19, brain injury and neuroinflammation**

Vulnerable children are those with neurological diseases and lung problems, requiring respiratory care [66]. This situation is currently a priority with the advent of the new coronavirus disease of 2019 (COVID-19). This is a zoonotic virus, an enveloped RNA, which can be transmitted from a sick person to another by close contact through touch, handshake, droplets of saliva, sneeze, cough, phlegm and

It was first detected in December 2019 and became an epidemic in Wuhan, Hubei province, China and quickly spread to several countries on six continents [69]. On March 11, 2020, the World Health Organization announced that COVID-19 was characterized as a pandemic, threatening global public health and creating a record economic burden. Coronaviruses are a large family of viruses that cause diseases such as the common cold to more serious diseases, such as Severe Acute Respiratory Syndrome (SARS). A new coronavirus is typically a new strain of infec-

The new 2019 coronavirus, coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) appeared after six other human coronaviruses. Four common human coronaviruses which cause light to moderate illness of the superior respiratory tract, including 229E (coronavirus alpha), NL63 (alpha coronavirus), OC43 (beta coronavirus) and HKU1 (beta coronavirus), were registered for the first time in the 60's [71]. Two other human coronaviruses are SARS-CoV and MERS-CoV, which cause grave infections to pulmonary lesions, known as Severe Acute Respiratory Sickness (SARS-C0V) and Middle East Respiratory Syndrome (MERS-CoV), respectively. The MERS-CoV outbreak occurred in 2012, starting in Saudi Arabia and spreading to other countries with a mortality rate of 37% [71, 72].

1.Asymptomatic Infection: without symptoms and clinical signs and normal thorax image, while the 2019 nCoV nucleic acid test is in a positive period.

2.Light: Acute symptoms of infection of the superior respiratory tract, including fever, fatigue, myalgia, cough, sore throat, coryza and sneezing. The physical exam shows pharyngeal congestion and absence of auscultatory abnormalities. Some cases may not have fever or only present digestive symptoms such as

3.Moderate: with pneumonia, fever and frequent coughs, especially dry cough, followed by productive cough, some may have a chest wheezing, but no obvious hipoxemia, with lack of air or dry wheezing and or wet wheezing. Some cases may not have signs or clinical symptoms but the Computerized Tomogra-

4.Serious: precocious respiratory symptoms, such as fever and cough, can be followed by gastrointestinal symptoms, such as diarrhea. The disease generally progresses for about one week and dyspnoea occurs, with central cyanosis. Oxygen saturation is inferior to 92%, with other manifestations of hypoxia

5.Critical: Children can rapidly progress to acute respiratory distress symptom or respiratory insufficiency and can also present shock, encephalopathy, myocardial or cardiac injury, coagulation dysfunction, and acute renal lesion. The

tious disease that has not been previously identified in humans [70].

**50**

#### *Advancement and New Understanding in Brain Injury*

mortality in the senior population and in people with certain comorbidities which are known since they have differences in their immune profile [83].

Comorbidity is present in more than 30% of cases of infection with SARS-CoV-2 [80]. Organized by related mortality rates, the chronic conditions in victims with the virus include cardiovascular diseases, diabetes, chronic respiratory diseases, hypertension and cancer. All of these conditions, in the long run, tend to make the immune system imperfect, both in innate and adaptive terms in the immune functions [84].

Brain injury caused by hypoxia increases the risk of developing epilepsy that is difficult to control. In the presence of infection by SARS-CoV-2, there is greater susceptibility to the occurrence of convulsions, increasing their vulnerability.
