Travel for Life: Risk Factors for Covid-19

Transmission of the Covid virus occurs via respiratory secretions and saliva. Droplets are expelled through the mouth or nose and can directly land on the mucous membranes (mouth, nose, eyes) of another person. Indirect transmission is also possible either from droplets landing on the skin of another person who then touches his or her mucous membranes or from touching a surface that has been infected.

Inter-individual clinical variability after respiratory infection with SARS-CoV-2 is immense. Most infected individuals (>98%) remain asymptomatic or develop mild, ambulatory disease.

"Patients with COVID-19 display a wide array of clinical manifestations and degrees of severity, ranging from flu-like symptoms to acute respiratory distress," said Robert E. Gerszten, MD. "While pre-existing conditions, particularly cardiovascular and metabolic disease, are risk factors for disease severity and outcomes, the underlying reasons that some people develop life threatening disease while others remain asymptomatic are not well understood."

Different Post-Infection Symptoms & Outcomes

What is it that makes some people very sick and other people hardly sick at all?

There are two major possibilities from the genetics perspective:^[23]
The genetic sequence of the virus itself: that some strains make people sicker than others
The unique genetics of each person who catches the disease.

After COVID-19 infection, some people^[5]

Requires hospitalization (<2%)

Some people develop pneumonia 1 to 2 weeks post infection and require hospitalization

Require intensive care (<0.5%)

Because of acute respiratory distress syndrome (ARDS) and/or the failure of other organs

Develop a severe systemic inflammatory response syndrome (SIRS) (<0.01%)

Which is closely resembling Kawasaki disease (KD)^[32]

Figure 1. Various outcomes due to different timing and dose of IFN response (courtesy: @BioRender & @annsea_park)

Risk Factors

The diseases and health factors that, according to a study done in Denmark, have the most influence on whether a patient ends up on a respirator after being infected with COVID-19 are in order of priority: BMI, age, high blood pressure, being male, neurological diseases, COPD, asthma, diabetes and heart disease.^[38]

Wang said the immunological factors the researchers have identified — a sluggish neutralizing-antibody response, deficient fucose levels on antibody-attached sugar chains, and hyperabundant receptors for fucose-deficient antibodies — were each, on their own, modestly predictive of COVID-19 severity. But taken together, they allowed the scientists to guess the disease’s course with an accuracy of about 80%.

Based on other researches, list of risk factors for Covid-19 also includes:^{[1,3,6,7,12,13}^]

3 Immunological factors identified

A sluggish neutralizing-antibody response, deficient fucose levels on antibody-attached sugar chains, and hyperabundant receptors for fucose-deficient antibodies — were each, on their own, modestly predictive of COVID-19 severity.
But taken together, they allowed the scientists to guess the disease’s course with an accuracy of about 80%.^[53]

Air pollution

Dr. Anita Shallal of Detroit's Henry Ford Hospital said long-term exposure to air pollution may impair the immune system and make it more susceptible to viral infections, while fine particles in air pollution may also act as a carrier for the virus and help it spread.^[47]

Blood type

A multivariate linear model confirmed the significance of the “B+” frequency predictor as protective against death by COVID-19.^[51]

High viral load environment (i.e., hospitals)^[41]

Japanese are advised to avoid crowds, clubs, and close contact in closed spaces, especially if it involves talking and singing.^[33]

Age (major risk)

Both mortality and critical disease are frequently reported in subjects >65 years of age but rarely in those <20 years of age.

Pre-existing conditions

See the next sub-section for details

Deficiency of Vitamin D

Among hospitalized COVID-19 patients, pre-infection deficiency of vitamin D was associated with increased disease severity and mortality.^[54]

Male^[3,6]

The risks for critical illness and mortality in male were estimated to be 1.5 times and 1.3 times higher than female.

The studies in early 1940s ascertained that females have enhanced capability of producing antibodies. This enhanced immune reactivity in females helps mount an effective resistance to infection and therefore females are less susceptible to viral infections.

The most high-risk group includes older males (see Fig. 2) with underlying chronic health conditions such as diabetes, cardiovascular conditions, obesity, and hypertension.
Male coronavirus patients with low testosterone levels are MORE likely to die from COVID-19, German hospital finds^[24]

However, the role of testosterone played in COVID-19 patients is a double-edged swords^[30]

Low testosterone levels in males have a direct correlation with the high probability of ICU admission and the worse disease outcome.
On the contrary, however, high testosterone levels can lead to thrombosis which is also one of the fatal manifestations in COVID-19 patients.

Testosterone is known to help regulate the body's immune response but when a man has low levels of testosterone, the immune system is not kept in check and can go haywire (i.e., cytokine storm) following infection.

Genetic variations^[11]

A higher risk in blood group A than in other blood groups and a protective effect in blood group O as compared with other blood groups.
A 3p21.31 gene cluster was identified as a genetic susceptibility locus in patients with Covid-19 with respiratory failure.
The genetic variants in the NKG2C/HLA-E axis have a significant impact on the development of severe SARS-CoV-2 infections^[40]
The major genetic risk factor for severe COVID-19 is inherited from Neanderthals^[29]

Compromised antiviral responses

Early robust IFN response is crucial^[13,14]

In the best case scenario, a rapid and robust induction of Interferon type I (IFN-I) should result in viral control and mild disease. (see Figure 1)

This may happen in young people, or with low viral exposure settings.

Neutralizing autoantibodies (auto-Abs) to IFN-I underlie life-threatening COVID-19 pneumonia.

A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
In these patients, adaptive autoimmunity impairs innate and intrinsic antiviral immunity.

Individuals that lack specific IFNs can be more susceptible to infectious diseases.

The timing of early antibody response is crucial^[12]

A delay in antibody responses could lead to more severe COVID-19 symptoms or even death.
Patients who developed neutralizing antibodies (NAb) before 14 days of symptom eventually recovered, while those who made NAb after 14 days developed severe disease and sustained higher viral load (i.e., viral load went out of control).

Neuro-COVID

This group of patients can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease

It is more prevalent in patients with severe COVID-19

The cerebrospinal fluid (CSF) of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells, which suggest compromised antiviral responses.

Increased plasma D-dimer level

There exists a significant correlation between increased plasma D-dimer level with an increased proportion of COVID-19 case severity.
A systematic review shows that a level of 3.48 μg/mL, which is over five times higher than in non-severe/survival cases, could result in poor outcomes in hospitalized COVID-19 patients.^[52]

Autoantibodies to immune-related or tissue-specific self antigens

The more severe the disease, the more autoantibodies COVID patients had.^[31]

There are many unanswered questions. How long do these autoantibodies last? What damage do they cause? How are they induced? Do they occur in #LongCovid?

Immune-related antigens

Some antibodies bound to interferons, chemokine and cytokines, while others bound to proteins expressed on the surface of immune and non-immune cells. Such antibodies could dampen body's immune response.

Tissue-specific antigens

Antibodies to various tissue-specific antigens were also found in organs like the central nervous system, vascular, connective tissues, liver, GI tract, etc. Such antibodies could drive damage in target tissues.

Figure 2. Older males with the highest risk

Pre-existing Conditions

Adults of any age with the following conditions are at increased risk of severe illness from the virus that causes COVID-19:^[17]

Cancer
Chronic kidney disease
Respiratory issues

Chronic obstructive pulmonary disease, chronic lung disease, moderate-to-severe asthma, history of tobacco use

Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
Moderately to severely immunocompromised (weakened immune system) people^[49]

Been receiving active cancer treatment for tumors or cancers of the blood
Received an organ transplant and are taking medicine to suppress the immune system
Received a stem cell transplant within the last 2 years or are taking medicine to suppress the immune system
Moderate or severe primary immunodeficiency (such as DiGeorge syndrome, Wiskott-Aldrich syndrome)
Advanced or untreated HIV infection
Active treatment with high-dose corticosteroids or other drugs that may suppress your immune response

Obesity (body mass index [BMI] of 30 kg/m2 or higher but < 40 kg/m2)
Severe Obesity (BMI ≥ 40 kg/m2)
Pregnancy

Based on what we know at this time, pregnant people are at an increased risk for severe illness from COVID-19 compared to non-pregnant people.^[44]

Sickle cell disease
Smoking

Cigarette smoke induces expression of angiotensin-converting enzyme 2 (ACE2), which allows SARS-CoV-2 to enter cells, and could possibly influence viral invasion beyond its negative effects on overall lung function.
A study from Cleveland Clinic’s Respiratory Institute is among the first to look at the cumulative effect of smoking on COVID-19 outcomes. And, it found that the more a patient was exposed to smoking, the more likely they were to have worse outcomes from COVID-19.^[46]

Thyroid abnormalities^[48]

Abnormal thyroid and hypothyroidism, but not hyperthyroidism, were associated with poor COVID-19 outcomes.

Type 2 diabetes mellitus

DM is a risk factor for a worse prognosis for COVID-19, which may be related to impaired innate immune response and greater susceptibility of patients with DM to a cytokine storm.^[8,9]

Pre-existing psychiatric diagnosis^[1]

The researchers at Univ. of Oxford have found that people with a pre-existing psychiatric diagnosis were 65% more likely to be diagnosed with COVID-19 than those without, even when the known risk factors for COVID-19 were taken into account.

Dementia

People with dementia had significantly greater risk of contracting the coronavirus, and they were much more likely to be hospitalized and die from it, than people without dementia, a new study of millions of medical records in the United States has found.^[39]

Travel for Life

Header

Saturday, December 26, 2020

Risk Factors for Covid-19

Different Post-Infection Symptoms & Outcomes

Risk Factors

Pre-existing Conditions

References

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