SARS-CoV2 or COVID-19, the New Invader
A pandemic is always underestimated and poorly understood, claiming victims after victims. It is becoming evident to us that the new COVID-19 is not only a respiratory disease but a disease that can mimic almost any condition. As more people become infected around the world, more information are shared about the disease.
A virus is a micro-organism even smaller than a bacterium that can grow or reproduce itself only in a living cell. Once it invades it, it destroys the defense mechanism and replicates itself at will, with fidelity or with errors creating mutations and allowing the virus to take a slightly different personality in each infected individual. This ability to change, renders also the treatment more difficult. Many common human infections as well as certain rare diseases are due to viruses.
Viruses exist under the form of independent particles (Virions) consisting in a genetic material (DNA or RNA) that encode the structure of a protein. They vary in shape and can be visualized under the optical microscope. A common cold is due to a rhino virus. AIDS is due to the HIV virus. All viruses are not the same kind but contain either DNA, either RNA in their genetic baggage. Herpes simplex and Hepatitis B viruses are both DNA viruses. The difference between the RNA viruses is the fact that they contain an enzyme called “Reverse Transcriptase”, permitting the DNA to be converted to RNA.
Three new RNA viruses have emerged in the turn of this century. Three Coronavirus SARS or SARS-CoV (China- November 2002), MERS (Middle East 2013) and finally SARSCoV2 or COVID-19 (China Dec 2019). These viruses most likely infect birds and mammals like bats and animals in the wet market but the virus has evolved from animals to humans. In humans, they can cause upper respiratory tract infections expanding from a common cold to more serious lower respiratory tract with pneumonia and severe respiratory illness. The CDC and the World Health Organization encourage the use of COVID-19 when referring to this new disease, a new coronavirus that has never been encountered before in humans. The name COVID-19 stands for “CO” means corona, “VI” means virus, ”D” means disease and 19 indicate the year of its discovery.
The general public has become familiar with the terminology SARS-CoV-2: “Severe Acute Respiratory Syndrome Coronavirus 2”. In short term to “SARS-CoV-2” is actually the virus that causes the disease “COVID-19”, remembering the SARS of the 2002-2003, a similar but different coronavirus. A virus acts as a submicroscopic infectious agent which has the ability to replicate only inside a living cell of an organism. All life forms can be involved: animals or plants or micro-organisms like bacteria. Description of pathogens infecting tobacco plants at the end of the 19th century has opened the field for scientists to discover many thousands of viruses.
Once infected, the host cell loses its defense mechanism and is forced to produce thousands of identical copies of the original virus. The origins of viruses are unclear but they are considered as a life form because they carry a genetic material, more they reproduce through natural selection although lacking cellular structures. They are often called “replicators”.
Viruses can spread in many ways using “vectors” by example. Diseases get transmitted from plant to plant by insects, or they can be carried by animals, like blood sucking animals. Influenza viruses are spread by coughing and sneezing. Norovirus and rotavirus cause gastroenteritis and are transmitted by fecal-oral route. HIV viruses is transmitted through sexual contact or by contact with an infected blood. HPV infection and viral hepatitis attack the immune response and result in chronic infections.
RNA virus like HIV and Hepatitis C are classified depending on their shape and behavior. DNA viruses are Herpes-viruses, adenoviruses, papoviruses, poxviruses, parvoviruses etc. while the RNA viruses include the picornaviruses (rhinoviruses) calciviruses, rhabdoviruses, retroviruses etc. Many of those viruses are host specific capable to behave in animal to human transmission.
An epidemic disease across a large region, crossing international boundaries or continents but affecting numerous people worldwide, is called a “Pandemic” (From the Greek Pan=All + Demos=People). Pandemic of Smallpox, Pandemic of Tuberculosis. The most fatal pandemic reported in human history was the “Black Death” 1331-1353 (Plague) who killed 75-200 million people in the 14th century. Another one in 1918-1920 was the Influenza pandemic (Spanish Flu) killing 50-100 million people. Others like the HIV/AIDS and the COVID-19 continue to claim victims. It starts mostly when animals are infected with a virus, later infect people, then move to the stage where the virus is also transmitted between humans locally and worldwide.
A new strain of coronavirus originated in Wuhan, Hubei province, China in late December 2019, or maybe earlier, has caused a cluster of cases with acute respiratory disease: a new coronavirus disease COVID-19. It looks nowadays that around 200 countries have been affected by this pandemic with major outbreaks in central China, Western Europe, Iran and the United States. It is only on March 2020 that the World Health Organization declared it a Pandemic after almost 4 million people become infected.
It is said that this virus lands on your nose, eyes or mouth allowing a “spike protein” on its surface to interact with a specific ACE2 receptor found in most organs in the body. The virus uses the living cell to multiply making millions of copies of itself, and becoming as virulent as the others. The virus can be inhaled or coughed out to infect others.
The Coronavirus paralyses the cells and stops them from calling for help in cutting all distress signals and in destroying its antiviral commands, allowing the virus to copy itself and infect the surrounding areas. The virus spreads before any immune responses like fever can be even noted. Many with mild or no symptoms find a way to fend off the virus especially if the symptoms are only respiratory. Once an individual becomes a victim of the virus at an entry point, the viral particles invade the entire body attacking the Gastrointestinal system and different organs.
A respiratory syndrome is almost the most important reason to visit the hospital looking for care. Others may have diarrhea and abdominal pain as well. To-date in this pandemic, it is noted that the COVID-19 has shown an aggressively to all part of the body that many have underestimated. Most infectious disease specialists would appreciate if I can jump on the opportunity to state that such infection has never been seen in recent years.
Once the virus is embedded in the body, the disease becomes severe and attacks any organ which contain ACE receptors, including the heart, the kidneys, the liver, the nervous system and the vascular system. This disease does not discriminate and every organ can be a target. Studies at the Neurology Department of the University of Colorado are being conducted on the Central Nervous System including the brain and the peripheral nerves. They hope to be able to explain the loss of taste and smell as a possible involvement of the nerve and subsequently the brain. So far, there are no conclusive evidences to establish such correlation with “SARS-CoV-2”, the actual name for COVID-19.
The infection can simulate a gastrointestinal disease with diarrhea and abdominal pain or be confused with a cold or the flu. Pink eye or runny nose, loss of smell and taste, muscles aches, fatigue, loss of appetite, nausea and vomiting. Body rashes with swelling and redness can be also seen. Cases of Guillain-Barre syndrome and fainting smells, seizures with hypoglycemia and confusion are seen. Cutaneous lesions have been reported and recent headlines that young children have been admitted with serious inflammatory conditions similar to Kawasaki disease with fever, rashes, red eyes, swollen lymph nodes and hands have surprised pediatricians. In more severe cases cardiac arrhythmia, heart failure and kidney damages are also expected. One fatality has been recorded in the USA in a 7 month-old child.
Viral particles are easily found on pathologic specimen during autopsies, in the nasal passage and the throat, in secretions like tears, stools and in multiples organs like the kidney, liver, pancreas and heart. New reports have also found evidence of viral particles in the spinal fluid suggesting possibly meningitis and guess, the virus is also discovered in the semen. Can it be transmitted sexually like HIV or Hepatitis C? We will need to wait for an answer.
Severe damage to the lungs can overstimulate the immune system through a flood of chemicals called cytokines, referring to a “cytokine storm”. This storm is manifested by a rapid drop in the blood pressure responding to the viral load forcing inflammatory cells to invade the lungs, heart, kidneys and brain. Some will suggest that the storm may contribute to a sudden decompensation in the disease.
Many specialists are discovering that a phenomenon of abnormal clotting or thrombosis may play a major role in the pathophysiology and the severity of the disease. Blood clots, deep vein thrombosis (DVT) in the legs have been described: A famous lead singer, Canadian born on Broadway underwent a leg amputation due to complications from COVID-19 explaining what can go wrong during severe infections. He was placed in an induced coma using machines supporting his heart, lungs and kidneys.
Not only pulmonary emboli (PE) are also seen but also clots are discovered in smaller arteries and multiple organs. They may result in strokes. These blood clots are seen in spite of patients being placed on blood thinners. An interesting study in the Netherlands has demonstrated that 31% of patients admitted with an infection due to the COVID-19, have developed blood clots while being on blood thinners. The reason for the clotting phenomenon is still not clear but it contributes directly to the rate of death. Compiling the damages caused by the cytokine storm and adding on the severity of the illness, the low level of Oxygen, the ventilators use and different drugs used in the treatment can harm vital organs like the heart, liver, kidney, brain etc.
The ACE2 receptor used by the virus to penetrate the cells is a key player in lowering the blood pressure and reducing the inflammation. It is also important to know that targeting and blocking these receptors may actually worsen the blood pressure, increase the risk of heart failure and kidney injury while finally worsening the lung problems. Medications targeting the immune response to lower the risk of cytokine storm may render also difficult the killing of the virus. Timing appears to be the key in any treatment strategy. Vitamin C and D are suggested as supplement, especially in the black population because of their high prevalence in morbidity leading to death.
When dermatologists discovered another condition involving the toes and the fingers with redness, in relation to this pandemic, they rapidly coin the name of “COVID-19 toes” or Pernio to the lesions and they found it directly related to blood clots involving the small arteries. This condition is believed to be found exclusively in children.
Finally, what are the long terms effects of the disease on survivors? What does life will look like after being a ventilator dependent-patient for so long? What about kidney disease and the need for dialysis? Will heart, kidney or lung functions decline with time? We are not sure on the way one will react after clearing this infection. We would also expect to develop at least a short term immunity after recovering from the disease or should we guess that the virus continues to hurt through a latent infection like we see with Chickenpox. Yes!!! Dormant in the body only to re-emerge periodically as Shingles or as a chronic infection like Hepatitis B, causing progressive and long term damage.
I will avoid entering the world of controversies about treatment because so much is being offered to the one suffering from COVID-19 while studies are being pursued. The convalescent plasma, a biologic agent is expected to act on immunity. Chloroquine (Aralen) or Hydroxychloroquine (Plaquenil) are known as anti-malaria medications which have been in use for long periods. They can be mixed with Zithromax and Zinc or Magnesium to bring promising results. Lopinar, an angiotensin receptor blocker, Tocilizumab a monoclonal antibody that bind to interleukin IL-6 receptors, Losartan is a receptor blocker in the treatment of High Blood pressure, Redemsivir, a nucleotide analog that inhibits viral RNA polymerases can be given in a 9 days course intravenously with a starting dose of 200 mg followed by 100 mg/day for a week, has shown promising results.
So many other drugs and medications including anti-coagulants have played a role in the treatment of the disease. We will have to wait later the formulation of a more definitive approach.
I just want to conclude in reflecting a little, on the time of my young years in training:
The few months passed in confinement has affected my life as a physician, orthopedic surgeon and Traumatologist. COVID-19 has punched us and bought the world to its knees. Behaviors have changed, business have closed while our health is menaced. This pandemic has modified deeply our way of living. We have lost so many colleagues in the front line of the fight against this pandemic and many parents or friends have contracted the disease or still fighting for their lives. Their struggle became our struggle.
I remember entering the United States in search for a residency program and the menace of a new disease HIV with its stigma on the Haitian Diaspora, associated to the disease of the 4H. The HIV/AIDS put a toll on the medical community as well.
I was unable to contain my joy when I got accepted at Howard University Hospital, in General Surgery and then in Orthopedic surgery. Proud of being a young physician at a so prestigious University Hospital, I felt like being in a twilight zone. We knew so little about protection and our medical knowledge was obviously deficient. I have in memory an encounter with a patient, victim of a crush injury to the right hand with bleeding from an open fracture, referred to me for an evaluation. I approached him without proper gear and no gloves. The patient then mentioned to me that he was HIV positive. It took me time to understand his message. We did not know much about the disease then. nor were we trained sufficiently to handle these cases. I appreciated so much his gesture that I made me available to personally care for him anytime he would return for follow-up care.
I do not think that we were better prepared to handle such high risk patients as surgical residents but actually nobody really knew much about the disease. We learned soon about the life expectancy of the virus with a drop of blood on a table compared to the one from hepatitis C. While we had more fear for hepatitis C, the HIV was most potent. But we understood that the Hepatitis C virus would last longer on a surface. Indeed, nowadays one can expect an almost full recovery in both diseases because of advances in their treatments. Family members, friends have also perished suffering from these diseases, the same way we are losing them actually, with the COVID-19.
I would guess that the fear expressed by our young residents and interns approaching the first patients during this COVID-19 pandemic in February 2020, was similar to what we felt while facing our patients during the HIV/AIDS epidemic. They needed to learn like us, new sets of skills and apply them in approaching such patients.
In today’s world, given what we know about COVID-19, I suppose I would have already unknowingly carried the pathogen from one patient’s room to another. But being a good physician requires one to be both reasonable and compassionate enough, to differentiate the possible from the likely. We needed to proceed with caution without a crippling anxiety.
In the case of COVID-19, I imagine that a new generation of students and residents will learn how to prevent airborne illness and, more importantly, how not to spread the pathogens to others. In fact, better hand-washing techniques has led to a drop in other nosocomial infections that cause significant morbidity and mortality, such as MRSA and C. difficile. We know well how the proper disposal of sharps in the HIV era has decreased the risk of catching hepatitis from needle sticks. For us, they were lessons learned while responding to a crisis.
COVID-19 is not as deadly as AIDS was, but its sudden onset, casual transmission and virulent attacks, have rendered the serious pulmonary complications, a much more tangible threat. I am sure that our young physicians have mastered new ways to examine patients at bedside in order to avoid contaminating others. HIV/AIDS was also a deadly epidemic when I started my residency program. I faced my fears and succeeded in becoming an orthopedic surgeon. I followed the Hippocratic Oath and cared for many who suffered from HIV, Hepatitis C or other threatening diseases, allowing me to rapidly improvise and perform in the best of my ability. It will not be the last pandemic to affect the world but I am confident that a newer generation of physicians have already developed the proper techniques to deal with the challenge.
To all the friends I lost in the fight against this new pandemic, to all the healthcare providers and personals, victims of the COVID-19, I want to dedicate this page and wish them a full recovery. I know of so many, still respirator dependent hanging to life and not knowing what tomorrow will bring. This viral pandemic is here to stay longer than two years or more. It may attack more the poor, the sick, the old or anybody with comorbidities but there will be a time when immunity will help us fight more effectively this invasive disease.
Maxime Coles MD (5-8-2020)
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