Covid -19 ” Evolving concepts and Emerging treatment modalities”

Dr Arvind Kohli
A month and half ago when our country went into preparatory mode for the first wave of corona virus cases, many doctors felt confident they knew what they were dealing with. Based on early reports, Covid-19 appeared to be a standard variety respiratory virus, albeit a contagious and lethal one with no vaccine and no treatmentcalled as SARS-CoV-2 which belongs to the betaCoVs category. It has round or elliptic and often pleomorphic form, and a diameter of approximately 60-140 nm.
Like other CoVs, it is sensitive to ultraviolet rays and heat. Furthermore, these viruses can be effectively inactivated by lipid solvents including ether (75%), ethanol, chlorine-containing disinfectant, peroxyacetic acid and chloroform except for chlorhexidine.
Covid !9 presents with clinical manifestations of
Mild disease: having non-pneumonia and mild pneumonia; this occurred in 81% of cases.
Severe disease: usually presents with dyspnea, respiratory frequency ? 30/min, blood oxygen saturation (SpO2) ? 93%, PaO2/FiO2 ratio or P/F [the ratio between the blood pressure of the oxygen (partial pressure of oxygen, PaO2) and the percentage of oxygen supplied (fraction of inspired oxygen, FiO2)] < 300, and/or lung infiltrates > 50% within 24 to 48 hours; this occurred in 14% of cases.
Critical disease: presenting with respiratory failure, septic shock, and/or multiple organ dysfunction (MOD) or failure (MOF); this occurred in 5% of cases.
Since then there has been an exponential growth in number of cases all over the globe and it has been established that Covid-19 attacks not only the lungs,but other organs like Liver ,Intestines, brain and Cardiovascular System for which.Blood is the transport system, responsible for moving nutrients to the cells and waste away from them and it is still a matter of emerging evidence whether blood complications in Covid 19 are a result of a direct assault on blood vessels, or a hyperactive inflammatory response to the virus by the patient’s immune system.
Based on observations in USA, Spain, Italy, France and UK,where there has been high mortalities and from autopsies of lungs involvement in COVID 19 , which revealed evidence of pulmonary thrombosis which is not typical ARDS , but more alarming that it is patient hypoxemia that is not responding to PEEP but high oxygen flow.
The COVID 19 virus attacks Haemoglobin ‘s beta chain, dissociates heme, removing iron and converting it to porphyrin. The virus can dissociate oxy-Hb, carboxy-Hb and glycosylated Hb. Like methemoglobin, the COVID 19 virus structural protein, sticks to heme and displaces oxygen which in turn releases iron-free ion , that leads to toxicity and causes inflammation of alveolar macrophages- that results in bilateral CT scan changes as it is a systemic response. Lung inflammation results from the inability of both oxygen and CO2 exchange, leading to the ground glass on x rays,
COVID-19 causes prolonged and progressive hypoxia by binding to the heme groups in the red blood cells. And Patients are desaturating due to failure of the blood to carry oxygen.
This process lead to multi-organ failure and high mortality.The lung damage seen on CT scans is due to the oxidative iron released from the haemolysed red blood cells which in turn overwhelm the natural defences against pulmonary oxidative stress and causes what is known as Cytokine storm.
The freely floating iron ion are highly reactive and causes oxidative damage. This always happens physiologically and naturally to a limited extent in our bodies and such cleanup is a defence mechanism to keep the balance.The Three primary Lung defences to maintain “iron homeostasis”, 2 of them are in the alveoli.
The first of the two are macrophages that roam around and scavenge up the free radicals of the oxidative iron. The second is a lining on the epithelial surface which has a thin layer of fluid packed with high levels of antioxidant molecules such as ascorbic acid (Vitamin C) among others.
When too much iron is in circulation, it begins to overwhelm the lungs’ counter measures and thus begins, the process of pulmonary oxidative stress. This leads to damage and inflammation, which leads to the so-called Cytokine storm; this can be documented on high-resolution CT scans of lungs.
The liver is attempting to do its best to remove the iron and store it in its ‘iron vault’. Only its getting overwhelmed too. It is starved for oxygen and fighting a losing battle from all the haemolysis haemoglobin and the freed iron ion. The liver will start releasing alanine aminotransferase (ALT) which is the second of 3 primary COVID 19 severity score indicators.
Tackling the Covid Patient
Based upon these revelations. new treatment protocol needs to be established There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. The treatment is symptomatic, and oxygen therapy represents the major treatment intervention for patients with severe infection
COVID 19, SARS2 is not ‘pneumonia’ and ARDS.presents at late stage Hence Invasive ventilation may not be the solution, but emergency intubation can harm and result in more damage, not to mention complications from tracheal scarring and stiff lung during the duration of intubation.
Blood Transfusions and Plasmapharesis, Patients require frequent blood transfusions or plasmapheresis. Which shall help in ameliorating the cytokine storm .and taking care of milieu of the blood
Role of HydroxychloroquinineHCQ Role of this drug has been advocated by many physicians both in management as well as prophylaxis A drug does not need to act on the pathogen to be effective directly. Chloroquine is understood to compete for the binding to porphyrin. Chloroquine lowers the blood pH and interferes with the replication of the virus
Retroviral Drugs
Favipiravir binds to the virus envelope protein with very high affinity, prevents entry into the cells as well as binding of the structural protein to porphyrin.
Tolicizumab: It is a humanized IgG1 monoclonal antibody, directed against the IL-6 receptor and commonly used in the treatment of rheumatoid arthritis has been used in patients in Italy
If free radicals scavengers and iron chelating agents are added to the protocol of management, it may lessen the inflammation process. .
Various management strategies all over world recommend that Aim should be to Inhibit viral growth and replication by the adjuvant use of HCQ+ZPAK+ZINC or other retroviral therapies . The less virus load patient shave, the less haemoglobin is losing its iron, the less severity and damage with the prevention of cytokine storm
Hyperbaric oxygen therapy (HBOT)
The patient will receive 90 minutes of hyperbaric oxygen at 2.0 ATA with or without airbreaks per the hyperbaric physician and five therapies are given.An aerosol of prostacyclin as pulmonary hypertension modulator is useful adjuvant
HBOT in the treatment of pulmonary hypoxia is emerging as a safe and clearly superior treatment compared to other methods such as mechanical ventilation and extracorporeal membrane oxygenation (ECMO) for pulmonary oxygenation. .
Mechanical Ventilation : The main point that patients will require ventilators if they present late with multi-organ system failure/ARDS to tie them over this life or death scenario. However, intubation is futile unless the patient’s immune system modulates the situation. Even If we reach the inevitably to ventilate, it must be done at low pressure but with maximum oxygen flow. Care should be taken to maintain euvolemia for preserving renal functions
Sepsis represents a life-threatening organ dysfunction caused by a dysregulated host response to suspected or proven infection, with organ dysfunction The reference for the evaluation of multiorgan damage and the related prognostic significance is the Sequential Organ Failure Assessment (SOFA) score
Meanwhile, scientific research is growing to develop a coronavirus vaccine.but meanwhile.
PLASMA THERAPY is Emerging fast as therapy for Covid-19 sick. patients and various studies have shown that CP [convalescent plasma] therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia [the presence of viruses in the blood] in severe Covid-19 cases, The convalescent plasma therapy aims at using antibodies from the blood of a recovered Covid-19 patient to treat those critically affected by the virus.
(The author is CTVS Consultant SSH Jammu)