The COVID-19 Conundrum

Published on 12 August 2021

Photo by Edwin Hooper on Unsplash

COVID-19 is a puzzling disease.  According to the experts, the delta variant of SARS-CoV-2, which is wreaking havoc currently, is as infectious as chickenpox.  The virus is causing severe disease in some people and mild or no symptoms in others.  It spreads via the olfactory and gustatory pathways and impacts people with comorbidities like heart disease, diabetes mellitus, and chronic lung disease.  Disease severity depends on genetic factors, viral load exposure, variant of the virus, as well as, age and socioeconomic status of the person.

Vaccine hesitancy

Novel technology tools along with unprecedented private and public funding have helped the scientists come up with vaccines for COVID-19 in record time.  But vaccine hesitancy is becoming a threat to global health.  COVID-19 vaccines are efficient in providing protection and help avoid hospitalization and death due to the disease.  There are side effects or adverse events after immunization (AEFI), but they are rare, and vaccines are highly beneficial.  The antibodies that appear after vaccination are the strong indicators of what is known as the correlate of protection against the infection. The generation of neutralizing antibodies predicts the efficiency of vaccines.  Even vaccines that trigger the production of low neutralizing antibodies will help people navigate the pandemic better.  Vaccine misinformation and anti-science conspiracies should be nipped in the bud to prevent vaccine hesitancy.

Vaccine nationalism

Vaccine nationalism is creating a disparity in providing vaccines around the globe.  Rich countries with just 16 percent of the world’s population have so far bought nearly 60 percent of the vaccine supply.  Nearly 130 countries have not yet received a single dose of vaccine.  The wealthier global north is able to meet its target of vaccinating people compared to the poorer global south where there is a delay in vaccinating even the healthcare workers, leave alone the general public.  This is responsible for the emergence of new SARS-CoV-2 variants despite the travel restrictions and stringent public safety measures.  According to WHO, some high-income countries, like Germany and France, are planning to give a third dose as a booster to protect its vulnerable population.

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TRIPS Waiver

Vaccines and other products required for treating COVID-19 are patent-protected and hence are supplied by very few players.  Compared to conventional vaccine technologies, mRNA vaccines are beneficial, mainly due to easy scalability in production.

India and South Africa led an initiative at the World Trade Organization (WTO) to lift the intellectual property (IP) rights so that products to treat COVID-19 could be made available widely, which in turn could enhance the global production of vaccines.  Trade-Related Intellectual Property Rights (TRIPS) is a multilateral agreement on intellectual property (IP) rights, such as copyright, industrial designs, patents, and protection of undisclosed information or trade secrets.  It came into effect in January 1995.  There was opposition from the global north for the TRIPS waiver, especially from Germany.

Global collaborative action is the need of the hour for equitable distribution of vaccines if we are to tame the virus, reduce economic loss, and human suffering.  Vaccine hesitancy and vaccine nationalism needs to end.

COVID-19 and its myriad symptoms

The most common symptoms associated with COVID-19 are the loss of smell and taste.  Brain imaging studies have shown that the regions associated with smell and taste are affected, as well as, the regions associated with memory and multitasking.  Hearing impairment, burning sensation and fizzy electrical feeling of the skin, gastric upsets, blood clots leading to gangrene, cognitive decline, psychosis, delirium, strokes, dementia, severe neurological complications are being reported following COVID-19.  It can impact activities of daily living (ADLs) and the ability to be gainfully employed.

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A few children with COVID-19 are impacted by a condition known as a pediatric multisystem inflammatory syndrome (PIMS).  Guillain-Barré syndrome (GBS), an autoimmune disease of the peripheral nervous system, and its rare variant, Miller Fisher syndrome, are also being sporadically reported in adults as well as children with COVID-19.

It is everywhere!

COVID-19 has spread everywhere, from the remote tribal hamlets to the climbers scaling Mount Everest.  Of note, the first COVID-19 patient in India in January 2020 was an Indian medical student who returned from Wuhan University in China, the epicenter of the disease outbreak.

SARS-CoV-2 not only impacts the respiratory and immune systems but also other systems like cardiovascular, gastrointestinal, nervous, urinary, reproductive, endocrine, and even skin, hair, and nail of the integumentary system.  The virus is found in the outer lining of the respiratory tract, sweat glands of the skin, digestive tract, distal convoluted tubule of the kidney, and testicular epithelium.  It is transmitted not only through the nose and mouth, but also through the skin, urine, and feces.

Diabetes

Diabetes mellitus is a risk factor for developing severe COVID-19.  Novel coronavirus can also spontaneously trigger Type 1 diabetes in people.  Type 1 diabetes occurs when the body’s immune system destroys the insulin-producing cells in the pancreas, and this interferes with the regulation of blood sugar in the body.  In Type 2 diabetes, although insulin is produced, the cells become insulin-resistant, leading to a rise in blood sugar.  In the pancreas, beta cells produce the hormone insulin which reduces blood sugar and alpha cells produce the hormone glucagon which increases blood sugar.  A balance between these two hormones maintains blood sugar levels.  The novel coronavirus was found to infect the beta cells by binding with its ACE2 receptors and damaging the cells which control the blood sugar levels.

Fatty Liver

The liver carries out more than 500 functions in the body.  For a healthy liver, a well-balanced low-carbohydrate diet is crucial.  A fat build-up in the liver causes fatty liver disease or steatosis.  Excessive alcohol intake severely damages the organ.  Even in people who drink little to no alcohol, there is a condition called as non-alcoholic fatty liver disease (NAFLD) that causes liver inflammation and scarring of the liver, leading to cirrhosis.  Obesity is also a major cause of liver damage.  The COVID-19 lockdown has made the obesity epidemic worse.  Fatty liver is increasingly becoming more prevalent and a risk factor for developing serious illness with COVID-19.

Hypertension

Blood pressure is high when it is over 150/100 mmHg.  Normal rage is less than 120/80 mmHg.  The longer hypertension is left untreated, the weaker the immune system becomes.  It is a risk factor for COVID-19.  Common drugs for the treatment of hypertension include Angiotensin-Controlling Enzyme inhibitors (ACE-i) and Angiotensin Receptor Blockers (ARBs).  ACE2 receptors are the entry point of SARS-CoV-2 into human cells.  These receptors are extensively expressed in numerous tissues and organs like the heart, lungs, kidney, blood vessels, brain, gut, and testis.  The COVID-19 virus binds to ACE2 to infect cells, and ACE2 levels are increased following treatment with ACE-i and ARBs.

Cholesterol

High cholesterol can interfere with the blood flow and increase the risk factor for heart attack or stroke.  Treatment for high cholesterol includes a healthy diet, exercise, and drugs like statins which help lower the bad cholesterol or low-density lipoprotein (LDL).  Cholesterol in the cell membranes of viruses is responsible for facilitating viral infection.  It was found that people taking cholesterol-lowering drugs were found to fare well against the novel coronavirus. Lipophilic statins were found to be more protective than hydrophilic statins, which have difficulty permeating organs and crossing the blood-brain barrier.

Black Fungus or Mucormycosis

Mucormycetes, a group of fungi belonging to the family Mucorales, are responsible for mucormycosis, a shadow epidemic within the COVID-19 pandemic in India.  The molds are largely found in soil, abundant in decaying organic matter, air, water, and damp places.  The fungi causing the infection were found to be Rhizopus arrhizusRhizopus microsporus, Rhizopus homothallicus, and Apophysomyces variabilis.  The black fungus appears as black spots in the nasal cavity and mouth, along with teeth pain and distorted vision.  It can lead to severe infection in an immunocompromised person.  It was not present during the first wave of COVID-19 in 2020.  It not only impacts the COVID-19 patients on steroids and those with uncontrolled diabetes but also the asymptomatic without any comorbidities.  Steroids are effective in the treatment of severe inflammation, but excessive use for long can lead to secondary fungal and bacterial infections.

Green fungus

A case of green fungus or Aspergillus is also being reported.  It can impact the sinuses, blood, and lungs of immune-compromised people.  The spores of this fungus are commonly found in the environment, especially in heating or air conditioning systems.

White fungus

COVID-associated pulmonary aspergillosis (CAPA) also includes a lethal yeast infection in the blood caused by Candida auris or white fungus.  This is a hospital-acquired bloodstream infection.  Candida is found on many surfaces.

Long covid

Post covid syndrome (PCS) or long covid is seen in COVID-19 patients with symptoms lasting more than 12 weeks.  These long haulers exhibit severe fatigue, breathlessness, cognitive issues, and memory lapses, digestive problems, erratic heart rates, headaches, dizziness, fluctuating blood pressure, and hair loss.  Even before the pandemic, some people suffered from what is known as chronic fatigue syndrome (CFS) after a viral or bacterial infection.  These debilitating symptoms could not be medically explained.  Children too have long covid.  People get better and then relapse.  It is attributed to altered levels of cytokine, immune system imbalance, and neuronal dysfunction.

Hidden threats of COVID-19

It is not just the disease alone, but there are hidden threats that interfere with the quality of life.  Increased screen time, mobile phones as germ carriers, gadget addiction, sedentary lifestyle, poor eating choices, obesity, insomnia or corosomnia, increased electromagnetic field (EMF) exposures from wireless gadgets, and eye and sleep problems arising from excessive blue light exposure are a few.  Retinal vascular occlusions, drooping of eyelids, and sudden onset of double vision have increased since 2020.

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Doomscrolling on social media is not good for mental health and indulging in risky irrational behaviors has increased under the pandemic fatigue. The dominant emotion during this prolonged pandemic seems to be languishing according to the experts, and the remedy to languishing is flow, which is to be absorbed into a meaningful and purposeful challenge.  The key is to set small goals, maintain focus and avoid fragmented attention.

Mental health issues

Several mental health issues are on the rise due to COVID-19.  It includes prolonged grief disorder (PGD) due to bereavement or job loss, cave syndrome due to long-term isolation leading to an extreme version of social withdrawal called the hikikomori complex, chronic anxiety and stress, mood disorder, fatigue, depression, and pandemic trauma similar to post-traumatic stress disorder (PSTD) exacerbating suicidality and substance abuse.

When a body is stressed, it releases the stress hormone, cortisol.  The prolonged release of cortisol increases the risk of heart disease and problems with sleep, mood, anxiety, and depression.  Chronic stress can kill brain cells and shrink the size of the prefrontal cortex responsible for memory and learning.  Long-term grief increases inflammation and systemic damage to the body.  There is an increase in inflammatory markers, especially cytokine interleukin-6, which is linked to increased risk of heart disease, greater susceptibility to infection, and earlier health decline.

There is no vaccine for this sort of grief.  Relief measures include gaining a sense of purpose in life, meditation, faith work, prayer, music, psychotherapy, and medications.

Role of genes in COVID-19 severity

SARS-CoV-2 manifests differently in different people, both young and old.  The risks of contracting COVID-19 is being attributed to genetics.  COVID-19 in some healthy young people is due to genes having a deficient immune response in their X chromosome.

Some people with blood group “O” are less susceptible, while some with genetic variability of ACE2 receptor and human leukocyte antigen genes are found to be more susceptible.  It was also found that the expression of ACE2 increases with age in both males and females.  The ACE2 expressions in Asians were similar to other races.

General health, nutrition, viral load exposure, and virulence of the pathogen also play an important role.

Air quality matters

It is understood that people breathe the exhaled air of others in a room.  Crowded spaces with poor airflow, as in the case of bars, clubs, gyms, and places of worship, are super-spreader hotspots for COVID-19.  Improvement in ventilation is crucial in offices, schools, hospitals, and senior care homes.  Efficient air filters, avoiding recirculation of air, availability of fresh air, use of germicidal ultraviolet lamps, and routine monitoring of air quality with sensors can help immensely.  Experts agree that the carbon dioxide levels must be kept below 700 parts per million (ppm) in a typical room and sensors can be used to monitor the levels.

SARS-CoV-2 is a challenging riddle

“Because answers exist only to questions…..”
Photo by Ilkka Kärkkäinen on Unsplash

Blood clotting from the Johnson & Johnson and AstraZeneca vaccines is seen as a very rare side effect after immunization in young women.  Heart inflammation and myocarditis from the mRNA vaccines like Pfizer and Moderna are extremely rare side effects reported after immunization in younger men.  It is very important to be aware that COVID-19 is a much bigger risk than vaccine side effects.  Vaccines are overwhelmingly safe.

Bacteria, fungi, and viruses when stressed undergo frequent mutations.  This is an evolutionary mechanism to cope with a changing environment.  Coronavirus under stress can mutate and become more transmissible, impacting children and penetrating the species barrier between animals and humans.

A 90-year-old female patient from Belgium was found to be the first person infected with two variants of SARS-CoV-2, namely alpha and beta variants.  Drugmakers are racing to create new versions of their vaccines for better defense against the ever-increasing number SARS-CoV-2 variants.

Booster shots and mixing of two different vaccines, also known as heterologous immunization, are being tested to guard against the diminishing responses from vaccines.  Covishield-Covaxin cocktail has been found to provide better protection when compared to two doses of the same vaccine.  WHO terms it as a dangerous trend, since sufficient safety data is lacking.

Interferons are signaling proteins crucial for anti-viral defense.  Interferons suppress viral replication early in the disease. But later on in the disease, they can exacerbate harmful inflammation in some COVID-19 patients, forcing them to go on life support.  Viruses also have several proteins, which can trick the interferon and shut it down.  The anti-interferon genes of SARS-CoV-2 can shut down the production of interferons.

ORF8 protein of SARS-CoV-2 enables viral replication.  It does this by downregulating a molecule called Major Histocompatibility Complex-1.  Coronavirus removes this marker by producing ORF8 protein, which combines with MHC-1 and destroys it.  MHC-1 is normally present in the membrane of a healthy cell.  When a cell is infected, MHC-1 alerts the immune system.  This is also a pathway followed by the Human Immunodeficiency Virus (HIV) to get rid of this marker.  HIV was discovered in the 80s.  Although no cure has been found, there is effective antiretroviral therapy (ART) to control the disease and prevent its transmission to other people.  SARS-CoV-2 and HIV are different, but their mechanism of action seems to be similar.

There are several other questions regarding SARS-CoV-2.

Low-dose radiation (LDR) is the weakest mutagen and carcinogen.  It is also known to improve immune response and inflammation.  LDR treatment can prevent the virus from mutating into a drug-resistant form.  LDR targets the host immune reaction and does not target the virus directly. Can LDR be a treatment option for COVID-19?

Is a single CT scan equal to 300 x-rays?  Will it increase the risk of cancer for the exposed?

Can COVID-19 be detected by testing cell phone screens?

While several cases of Zika virus in pregnant women in India, human H10N3 bird flu and monkey B virus in occupational workers in China, monkeypox virus in a traveler in Texas, and Marburg virus in West Africa are being reported, influenza has virtually disappeared worldwide. Why did the seasonal flu disappear?

How did the states in Brazil with a large number of people who contracted dengue in 2019-2020 witness very few cases of COVID-19 and deaths?

According to research, “failed nasal epithelial anti-viral immunity” may be the reason for severe COVID-19.  The viral replication begins in the epithelial cells lining the nasal cavity. Could this be the reason why some fall ill and some don’t? Could boosting immune response in this initial viral entry point avoid the infection altogether?

How did SARS-CoV-2 acquire a furin cleavage site at the S1-S2 junction?

How does this virus possess the arginine codons, not present in other beta-coronaviruses?

Where did the bat coronavirus RaTG13, the closest relative of SARS-CoV-2, originate?

There are known knowns. These are things we know that we know. There are known unknowns. That is to say, there are things that we know we don’t know. But there are also unknown unknowns. There are things we don’t know we don’t know.

Donald Rumsfeld

There are many unknown unknowns about the novel coronavirus causing COVID-19.


Further Reading

Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2 (20 April 2021): “Our data shows that while anti-NC antibodies provide long-lasting evidence of viral exposure or infection, about 20% of seropositive individuals lack meaningful neutralization activity after 5–6 months.”

WHO Statement on advancing the next series of studies to find the origins of SARS-CoV-2 (12 August 2021): “The International Scientific Advisory Group for Origins of Novel Pathogens, or SAGO, is a new advisory group for WHO, which will be responsible for advising WHO on the development of a global framework to systematically study the emergence of future emerging pathogens with pandemic potential.”

The animal origin of SARS-CoV-2 (17 August 2021): “Trading of animals susceptible to bat coronaviruses is the likely cause of the COVID-19 pandemic.”

Rogue antibodies involved in almost one-fifth of COVID deaths (31 August 2021): “Antibodies that turn against elements of our own immune defences are a key driver of severe illness and death following SARS-CoV-2 infection in some people, according to a large international study. These rogue antibodies, known as autoantibodies, are also present in a small proportion of healthy, uninfected individuals — and their prevalence increases with age, which may help to explain why elderly people are at higher risk of severe COVID-19.”

CALL OF THE WILD: Why many scientists say it’s unlikely that SARS-CoV-2 originated from a “lab leak.” (2 September 2021)

Kids and COVID: why young immune systems are still on top (7 September 2021): “Innate immunity might be the key to why children have fared better with the virus. But the Delta variant poses fresh unknowns.”

Our mobile phones are covered in bacteria and viruses… and we never wash them (14 September 2021)

Coronaviruses with a SARS-CoV-2-like receptor-binding domain allowing ACE2-mediated entry into human cells isolated from bats of Indochinese peninsula (17 September 2021)

Last Updated on 19 September 2021

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