Researchers have found that Down syndrome (DS) is associated with a 10-fold increased risk for COVID-19-related death. This is new information because this condition is not included in the lists of underlying health conditions that increases the risk of severe complications.
Global coronavirus infections have passed 58 million, meanwhile, the global coronavirus death toll exceeds 1.38 million according to researchers at Johns Hopkins University.
Researchers from the University of Oxford, the University of Nottingham, the London School of Hygiene & Tropical Medicine, and the University College London studied a cohort of 8.26 million adults through a QResearch database to evaluate if Down syndrome is a risk factor for death from COVID-19. The authors found an estimated 4-fold increased risk for COVID-19-related hospitalization and a 10-fold increased risk for COVID-19-related death in persons with Down syndrome. They stress this novel evidence should be used by public health organizations, policymakers, and health care workers to strategically protect vulnerable inpiduals.
What is Down syndrome?
DS is the most common chromosomal condition, occurring with a rate one in every 700 live births .DS occurs when an inpidual has an extra copy of chromosome 21, this additional genetic material alters the course of development and causes the characteristics associated with DS. The incidence of births of children with DS increases with the age of the mother.
People with DS have an increased risk for certain medical conditions such as congenital heart defects, respiratory and hearing problems, Alzheimer's disease and thyroid conditions. Many of these conditions are now treatable, so most people with DS lead healthy lives
The Immune System in DS
Many publications have reported abnormalities of the immune system in people with DS, particularly with respect to immunodeficiency and to autoimmunity.If the immune system is impaired, the resulting immunodeficiency leaves the inpidual more susceptible to infection, usually recurrent and often of greater severity.
Immunodeficiencies can be primary (due to a genetic deficiency) or secondary to other processes. Primary immunodeficiencies are very rare and usually very serious. Secondary immunodeficiency is very common and can be caused by many things such as malnutrition, stress, drug treatments, other disease processes or indeed other infections. Secondary immunodeficiency can range from the trivial to the very serious and can be transient or long lasting.
A well-nourished inpidual with DS, living in the community, in good housing and free of other diseases will not suffer the rates of infection associated with a defined primary immunodeficiency.
It has been widely observed that pneumonia, other respiratory infections and gastrointestinal infections are more common in inpiduals with DS, particularly in very young children.
Humoral Immunity is Abnormal in DS
Humoral immunity secretes antibodies to fight against antigens, whereas cell-mediated immunity secretes cytokines and no antibodies to attack the pathogens. Deficiencies in humoral immunity would be expected to result primarily in increased bacterial infection. The Humoral immunity is rapid or quick in their action against antigens, while the Cell-mediated immunity show delay though permanent action against any pathogens
Amongst the immunological findings which have been reported in DS are: decreased neutrophil and monocyte function (chemotaxis, phagocytosis and the oxidative burst, lowered (in infants) or raised (in adults) immunoglobulin levels, raised IgG1 and IgG3 but lowered IgG2 and IgG4 in some DS adults and children. Specific antibody responses may be lowered upon immunisation in DS people.
Cellular Immunity is Defective in DS
Cell-mediated immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.
Cell-mediated immune responses involve the destruction of infected cells by cytotoxic T cells, or the destruction of intracellular pathogens by macrophages .The activation of naive T cells in response to antigen, and their subsequent proliferation and differentiation, constitutes a primary immune response.
Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in destroying virus-infected cells, intracellular bacteria, and cancers.
Cell-mediated immune responses play a critical role in combating viral infections. They are comprised of T-cell responses, which fundamentally differ from antibody (humoral) responses in the way they bring about infection control. The cardinal trait of cell-mediated responses is that the physical presence of reactive T cells is required for immunity, whereas humoral responses are conferred by the presence of soluble antibodies. T cells, together with B cells, form the adaptive immune response to viral infections. The hallmarks of adaptive immunity include antigen specificity and memory. These features allow T cells to elaborate responses which specifically target the numerous viruses which may infect the host. The ability to establish long-lived immunological memory provides a unique mechanism to better protect the host during subsequent viral exposures.
Cell-mediated immune responses are dynamic, perse, and display a broad range of phenotypic and functional properties. Deficiencies in cellular immunity would be expected to result primarily in increased viral infection. Inpiduals with DS suffer from increased incidence of respiratory infections.
The presence of the gene for a superoxide dismutase (SOD) on chromosome 21 might be expected to adversely affect the functions of phagocytes which use superoxide to kill microorganisms.
Airway Obstruction
Airway obstruction is extremely common in DS ,due to mid-face hypoplasia, tongue enlargement and mandibular hypoplasia . The small upper airway, combined with relatively large tonsils and adenoids, contributes to airway obstruction and increases susceptibility to infections. Up to 80% of children with DS experience hearing loss, leading to difficulties in speech and language development .
Prolonged Course of Respiratory Infections
Even though some DS children may not present with frequent infections, the course of their infection illnesses might be prolonged and have increased severity compared with non-DS children. The median length of stay and cost of admission for DS children may be two to three times greater than the non-DS subjects. A higher incidence of acute lung injury secondary to pneumonia was found among DS children when compared to normal control children.
A review of a large cohort of DS children in Sweden and Denmark revealed a 12-times increased risk for mortality due to infections, especially septicaemia. This excess of mortality was consistent with data from a recent study in which DS children showed a 30% higher risk of fatality secondary to sepsis when compared to other children hospitalized for sepsis.
There is increased frequency and severity of respiratory tract infections in DS children. These are predominantly ear infections; however, pneumonias occur frequently in children younger than 5 years of age and are likely to require hospitalization. Lung disease might be of more prolonged duration. In addition to respiratory tract infections, periodontal disease is another condition of infectious aetiology that occurs frequently between 58% and 96% of inpiduals with DS.
Vaccine Response
The response to vaccination is varied in children with DS. This may have significant clinical consequences for a high-risk cohort more prone to severe respiratory tract infections and hospitalizations from vaccine preventable diseases like influenza. There is also evidence that despite initial adequate titers, the immune response may wane over time and that long-term immunity in DS may not be preserved as well as controls. Therefore, immunization against respiratory pathogens should be delivered routinely to ensure robust/adequate immunity is maintained. Tailored vaccination programmes may need to be considered.
Follow the latest news on Google News
