Lessons learned from COVID-19 Infection?

Nine months already has passed since the virus SARS-CoV-2 has claimed its first victims in the USA. We can remember the way our healthcare providers at different hospitals started learning how to treat the critical ill. Then, we found out that the disease was spreading out mainly person to person in closed contact (less than 6-10 feet) through respiratory droplets from coughs, sneezes etc. Indeed, we have lost since, more than 198,000 human lives while some 6,700,000 persons in the USA have been infected.

The CDC has published and revised so many guidelines and protocols. We may believe that the pandemic although has slowed down while the SARS-CoV-2 virus has mutated in different ways without becoming more virulent. Schools are re-opening their doors, business are trying to survive but we are still learning about the COVID-19.

We have lost so many family members, friends, colleagues and we are asking what will happen to the survivors of this new Coronavirus. Hospital and emergency rooms for a while were full of patients and often it was difficult to assure their successful treatments. This dramatic situation appears to have eased, creating perhaps a false assurance in the public. People become tired of the confinement and refused at time to wear masks for the protection of others or for their own safety.

Progress:

At the end, we distinctly learned how to describe 3 phases in the evolution of this viral disease which has spread through a pandemic:

1- A prodromal phase in which there is a “cytokine storm” which is manifested by the reaction of the body to the invasion of the virus, producing typical symptoms of elevation in temperature, coughing, shortening of breath, body ache etc. We have learned that the best approach at that phase was to prescribe antibiotics like Amoxicillin or Zithromax in the goal of avoiding any respiratory complications like a pneumonia. We added bronchodilators, nebulizers or steroid-puff inhalers to ease the reactive inflammatory process. The addition of Zinc and Chloroquine or Hydroxychloroquine has shown in many institutions in Europe and the United states (Yale University hospital) beneficial effects.       More clinical studies are expected to resolve present dilemma among physicians about possible heart toxicity.

2- The second phase coincides to the viral replication when the virus invades the lungs and different organs in the body. It is believed that a cleavage of the polyproteins into RNA-dependent to RNA Polymerase facilitates the mechanism. Simultaneously, an Angiotensin-Converting Enzyme 2 acts as the main receptor for SAR-CoV-2 on the alveolar epithelial cells allowing the conversion of Angiotensin1 into Angiotensin 2. The virus multiplies and forms identical copies, attacking different organs. The go-to medication is then “Remdesivir” (Adenosine Analog) to fight the duplication of the virus. Additionally, Blood thinners like Heparin, Coumadin, Lovenox etc. are strongly recommended especially in young patients to avoid vascular insults like strokes, thromboses and other vascular accidents.

3-  The third phase deals with the most advanced aspect of the disease when respiratory decompensation force the physician to place a patient under a respirator/ventilator. The go-to medication at his phase is “Dexamethasone” which was found to reduce the rate of death especially in front of a patient with multiple organ involvement and failure.

4- We learned how to use efficiently Convalescent Plasma transfusions of patients who have recovered from the disease, bringing immunoglobulins (antibodies) to the recipient. There may be risk of anaphylactic reaction or even transmission of the virus, infection and anaphylactic shock etc.

5-  An immune based therapy with Interferons Alpha and Beta have been tried with no conclusive data. The Interleukins I and VI, cytokines found in the macrophages and monocytes are also under investigation in many institutions around the world. Some have imposed the use of Lopinar or Ritonavir (HIV Protease Inhibitor) to ease the symptoms of the disease. We have learned that the virus SARS-CoV-2 infestation triggers changes in the level of “Ferritin”. The higher the level, the higher the mortality rate.

6- Stem cell therapy has been implemented in cases of patients with multiple organ failure. Recently one lung transplant was successfully performed in a Chicago IL hospital.

7- Finally, there is a lot of hope generated by the new vaccines which will work at exposing the recipient’s body to an antigen in the goal of training the immune system to fight the invading organism. Many vaccines are using a weakened or a killed version of the viruses to stimulate the formation of these antibodies. To date, more than 20 companies around the world are trying to achieve these goals.

During MERS (Middle East Respiratory Syndrome, 2013) pandemic, it was demonstrated that corticosteroids was detrimental to the well-being of the victims because the drug was delaying the viral clearance. Although SARS- CoV2 (China 2019) do present similar genetic resemblance to MERS and SARS-CoV1 (China 2002), “Dexamethasone” or “Methilprednisone” as anti-inflammatory medications were found to be life saver in COVID-19.

We applied these principles to the actual pandemic at the beginning of the crisis but it took us some times to realize that indeed these medications were saving lives in avoiding longer admission to our Intensive Care Units. It is now well admitted that “Corticosteroids” are becoming the go-to medication in the fight of advanced COVID-19.

The World Health Organization (WHO) has recently accepted the fact and released official statement to support the Corticosteroids effects on the survival rate of patients with severe disease.

Low doses of steroids medication for 10 days are now routinely used during hospitalization to help avoiding placing patients on a ventilator, lowering the risk of death and controlling the inflammatory process directly related to the viral infection, organ failure and death.

The go-to drug “Remdesivir” has been authorized by the Food and Drug Administration (FDA) for children and adults and has been used as well in pregnant women. This drug has allowed in-patient to recover in about 10 days of their hospitalization for COVID-19, avoiding the use of a ventilator.

The use of anti-Malaria and anti-Lupus medications Hydroxychloroquine/Chloroquine with or without Azithromycin and Zinc has been challenged but remain popular in African and European countries as well as in different institutions in the United States like the Yale Medical school. Controversies about the cardiovascular complications due to arrhythmias have reached the political world at the Eve of the new presidential elections.

Convalescent Plasma was granted approval in the treatment of COVID-19 in the hope that antibodies (Immunoglobulins) used to fight the aggression of the virus in an individual would be able to help others in gaining sufficient immunity to fight the disease.

The idea of using the plasma donated by survivors of a viral disease is not a recent concept and can find its origins during the Spanish Flu in 1918. On-going trials on patients receiving convalescent plasma are being performed all over the world to study the efficacy of the transferred antibodies in fighting the disease.

In a flash news this week, it was reported that a specific antibody (particle) to the COVID-19 was isolated at the University of Pittsburg. One has to believe that help is on the way.

Critical Care Physicians have also held off intubating any patient to minimize the use of mechanical ventilator after adequate oxygenation while “Remdesivir” was not yet in use. More, sedated patients on ventilators were found to have recovered faster when placed in a prone position or face down because of a better oxygen distribution throughout the lungs.

The majority of critical ill patients with COVID-19 presented with co-morbidity like old age, Obesity, Diabetes Mellitus, Chronic Obstructive Pulmonary Disease, Asthma, High Blood Pressure, Liver disease, Cardio Vascular Disease, Renal Disease, Cancer etc. Health inequity among Blacks and Hispanics has contributed to the problem. Recently a correlation between low level of Vitamin D3 and the COVID-19 has been identified. Papers from China and Italy have reported that this infection appears to be less common in people with blood type “O” and more common in people with the type “A”. The blood type appears to carry a receptor for the pathogen.

Strangely if one individual type “O” is protected against the SARS-CoV-2, he was found to be prone to Cholera bacillus.

Many are asking if this pandemic will ever go away. We are questioning the immunity acquired once exposed to the disease. Some countries are requesting an “Immunity passport” to be admitted or a test at least confirming that you are COVID-19 free of disease. We are not too sure if people in contact with the virus, will develop a long lasting immunity. Studies have shown that a patient who recovered from COVID-19 carries antibodies for 3 to 4 weeks until this defense mechanism disappear.

COVID-19 remains a puzzle that will require more time to resolve. While schools and business are trying to open timidly their doors, we are learning that the pediatric population has seen some children in need of hospitalization. Death among children under 15 of age have been recorded in France, Australia, England and United States.

More, rare cases of re-infections in the adult population have also submerged answering the question that you can have the disease twice. Indeed, people in Hong Kong, Europe and the United States (Nevada and Massachusetts) who have previously recovered from COVID-19 have become re-infected by a new strain of SARS-CoV-2. For some, the virus showed more virulence the second time. In any way, this virus is mutating like it was expected and the pandemic is still claiming life. We can’t let off our guards but we will need to keep taking the recommended precautions.

SARS-CoV-2 is certainly more contagious than any influenza virus but we will have to look at a way to survive especially when the next flu season is about to knock at our doors. Whether SARS-CoV-2 may become more infectious or more deadly, it must remain clear in our mind that this pandemic will co-exist with us for the next year to come. The virus may have mutated in many strains but it remains identical to the one which originated in Wuhan, China.

Keep practicing the usual social distancing, wear your mask once outside and wash your hands as often as you can. Stay away from the sick and avoid crowd. Stay away from parties in poorly ventilated places. Keep on doing your home exercises and enjoy your nutritious food.

Maxime Coles MD (9-15-2020)

References:

 

1-             Pozo Milton FACP: Prevention and Treatment of SARS-CoV-2, A Clinical Review (2020)

2-             Emerging coronaviruses: Genome structure, replication, and pathogenesis. J. Med. Virol. 2020 Apr; 92(4): 418-423.

3-             Ace2 Cell Biology, Regulation and Physiological Functions; The Protective Rm of the Renin-Angiotensin System (RAS) Academic Press; Boston.

4-             Fehr and Perlman, Coronaviruses: An overview of their Replication and Pathogenesis: Methods in Molecular Biology, 1282 pp 1-23.

5-             Li, Receptor recognition mechanisms of Coronaviruses: A decade of structural studies, Journal of Virology, 89 (4), 1954-1964.

 

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