THE treatment of Covid-19 is likely to boil down to good old nursing care. And here is why.
To understand how the coronavirus afflicts us, one has to appreciate that the basic unit of life is the cell. Cells organise into tissues, then organs (such as the lung); and then into systems and systems into the human being.
There are pathogens, that cause disease and which might be life threatening. They are parasites (protozoa, e.g. malaria, hookworms), bacteria (tuberculosis), fungi (candida, cryptococcus) and viruses (Ebola, polio, measles). We have mechanisms that protect us. Innate immunity, present at birth, fights pathogens, other than viruses.
For bacteria, fungi, and parasites, there are medications to treat them, should our immune defences fail.
These possess unique characteristics, not shared by the human cell. For example, bacteria possess a cell wall, which the human cell does not. Antibiotics can be designed to target the cell wall, killing bacteria without damaging the human cell.
However, viruses are so tiny that they cannot exist for long outside the human cell. They cause disease by entering the human cell and hijacking the cell machinery to multiply themselves, in the process killing the infected cell.
It is difficult to selectively kill viruses, without damaging the human cell. This is where acquired immunity comes into place. The blood has three types of cells: white, red and platelets, suspended in a fluid called plasma. The main job of white blood cells, or leukocytes, is to fight infection. There are several types of white blood cells, the most important of which are lymphocytes and phagocytes. B and T lymphocytes start the war against pathogens. When pathogens are detected by any of the lymphocytes, the B cells are stimulated to produce antibodies, which are proteins that attach themselves to pathogens, forming complexes called antigen-antibody complexes.
Although the antibodies find the antigens, they cannot kill them, so the T-cells come in to help. The T-cells call in phagocytes to help finish off the invaders, and then the phagocytes help clean up.
Whenever the acquired immune system overcomes a viral infection, B-lymphocytes keep it in its eternal memory. Should the same virus come into contact, the B-lymphocytes are primed to destroy the virus before it causes any illness. This understanding is the mainstay of preventing viral infections. Currently, there are no specific antiviral medications that can eradicate viral infections, but they can control the viral infection.
The acquisition of anti-viral defences is subject to the acquired immune system or learned immunity. This assumes there is enough time and ability for the immune system to develop the necessary defences. There are certain viruses that kill so fast, depriving the human immune system time to learn about them, with the Ebola virus being one.
Then there are viruses that can bypass the immune system altogether, by corrupting the whole human defensive mechanism, making the human being defenceless against viral and other pathogens; that is HIV. Immunisation is the mainstay of treatment of viral disease; entailing injecting a dummy version of the virus, similar to the disease-causing real virus, but without causing illness. It is such that when the human immune system encounters the real virus, it is already primed to destroy. Examples of successful vaccinations include measles, polio, rubella, etc.
The main job of red blood cells, or erythrocytes, is carrying oxygen from the lungs to body tissues and carbon dioxide as a waste product, away from the tissues and back to the lungs. The main job of platelets, or thrombocytes, is blood clotting. They group together to form a plug in the hole of a vessel to stop bleeding.
Although it has not been fully understood yet, Covid-19 afflicts the lungs in a way similar to high-altitude sickness, in a manner different from other lung diseases. In Covid-19, it is as if there is no oxygen in the air, hence patients gasp for breath and experience suffocation. This is as a result of a defect in the absorption of oxygen by the lungs due to damage to the air sac-capillary membrane of the lungs, where the gas exchange takes place.
Another feature is that the virus attacks red blood cells, impairing their ability to transport oxygen to the tissues (just like in carbon monoxide poisoning); while multiplying and destroying the red cells.
In Covid-19, initially the lung as a mechanical unit works well, but oxygen does not get to the tissues and patients need high concentration oxygen therapy delivered by non-invasive ventilation (NIV); where a breathing tube is not introduced into the throat. Such devices ensure continuous positive airway pressure (CPAP) and oxygen delivered by high-flow nasal cannula (HFNC); both delivered by face masks or nasal prongs. In other lung diseases, the lung as a mechanical unit does not work, and patients need mechanical ventilation early via a tube down the throat connected to the ventilation machine.
As the Covid-19 disease progresses, the patient will eventually struggle to breathe, with the lung as a mechanical unit failing, hence the patient requiring mechanical ventilation. There is a sub-group of patients who deteriorate without showing any of the usual course and parameters.
Patients might enter the hospital with high blood oxygen levels, engaging in happy conversation, only to be “gasping for breath” and intubated a few hours later.
The sudden turns for the worse are likely products of an “overly exuberant” reaction by the immune system as it fights the virus, called a cytokine storm, which occurs when the body overproduces immune cells and their activating compounds — cytokines; causing severe lung damage and organ failure. In part, this is triggered by putting the patient too early on a mechanical ventilator; hence the high mortality of Covid-19 patients put on mechanical ventilation, almost 80%. Clinicians are re-thinking their approaches after noticing more patients dying while on the mechanical ventilation in comparison to favourable outcomes for patients given oxygen through face masks.
Who gets Covid-19?
There is no way of predicting who might or might not get the severe form of the illness. About 98% of patients survive the illness and 2% succumb. Patients at highest risk are those above 65 years of age, who have a 20-fold risk of dying from it.
Also included are patients with pre-existing lung diseases like asthma, high blood pressure, heart disease and diabetes (diabetics are 10 times more likely to succumb to the disease than any other patients). It is not just the elderly or patients with underlying health conditions who can be fine one minute and at death’s door the next. It can happen to the young and healthy, including healthcare workers.
The commonest symptoms of the virus are fever, cough and shortness of breath. Other symptoms are sore throat, fatigue and headache. Less frequent symptoms are runny or stuffy nose and diarrhoea. Shortness of breath is the most frightening symptom, described as similar to suffocating. The work of breathing is good but there is still breathlessness. Bouts of coughing can take minutes, leaving the patient exhausted.
Treatment at home
Around 25% to 50% of patients experience no symptoms. The remainder with minor symptoms, can be managed symptomatically and supportively at home, provided their breathing is tolerable, particularly on exertion. The same barrier and distancing approaches must be maintained to minimise infection spread. Preferably, patients should be nursed in a single room with the windows open.
Fever patients are advised to drink cold water; not less than two litres per day to avoid dehydration. Patients are advised to take paracetamol, and use a fan. Ibuprofen is of second preference to paracetamol, as it might cause kidney damage; it can however be used with paracetamol. Patients should be given supportive treatment to ensure sufficient energy intake and hydration.
Cough is managed with simple measures like the intake of a teaspoon of honey, with cough syrups like codeine linctus being the next choice. The second choice is to use morphine sulfate oral solution. Patients are encouraged to avoid lying on their backs as this makes coughing up secretions ineffective. Breathlessness can trigger anxiety, making the breathlessness worse. A calm reassuring environment is encouraged. Patients remain unstable while they are still breathless, and preparations must be in place to take them to hospital at short notice, avoiding use of public transport in the process, and preferably warning the hospital in advance.
Treatment in hospital
For patients with moderate symptoms in at-risk groups (that is, aged above 65 years and/or with lung, heart and liver disease, diabetes, arterial hypertension); or alarming symptoms of breathlessness, treatment has to be individualised as much as possible, taking the patient’s wishes on board.
Hydroxychloroquine can be administered, if no contraindications can be given. Chloroquine can be a substitute for hydroxychloroquine. It must be noted that these medications have powerful side-effects. Hydroxychloroquine has been found to be even more effective when combined with the antibiotic azithromycin.
In severe disease, the antiviral combination kalentra (lopinavir or ritonavir); used for the treatment and prevention of HIV and Aids can be tried as a second line to hydroxychloroquine. In the setting of multiple organ failure, additional anti-viral therapy includes use of remdesivir (an anti-viral drug developed for the treatment of Ebola virus).
Tocilizumab, an antibody fragment used to treat inflammatory diseases like rheumatoid arthritis, has been found to have a favourable effect in the most critical patients suffering from persistent and overwhelming inflammation resembling cytokine storm, and can be used on patients requiring mechanical ventilation without evidence of bacterial superinfection.
For intubated patients, the judicious use of intravenous steroids like dexamethasone for a short course might be helpful.
Oxygen is indicated for patients exhibiting symptoms of breathlessness. If patients are still able to breathe on their own, the recommendation is to give them supplementary high oxygen concentration under low pressure, using a face mask or nasal prongs (CPAP and HFNC), which require machinery consisting of standalone units or in combination with proper ventilation machines, providing gentle ventilation, while buying time to recover with minimum additional damage.
Should the patient’s breathing be laboured, then mechanical ventilation is required, and the mortality becomes higher. Covid-19 patients behave in different ways, making the interpretation of the clinical signs baffling. Ordinarily, the normal partial pressure of oxygen in the arterial blood is near 100mmHg; the threshold for putting a tube and mechanically ventilating a patient is an arterial oxygen partial pressure of 88mmHg. This is what has guided most protocols. When a patient’s saturation drops to 70mmHg, they are confused and virtually unconscious, and a saturation of 60mmHg is incompatible with life. Yet for Covid-19 patients, they could be talking with a saturation of 50mmHg! And the moment they have a tube in they desaturate so rapidly to 10-20mmHg.
Worse still, their stress response is so atypical; heart rates may remain the same, rise or fall down. Blood pressure responses are difficult to predict. Clinicians are being guided by the patient’s state, not necessarily by established parameters of clinical measurements.
Observations such as these have prompted some physicians to ask whether standard respiratory therapy protocols for typical lung illnesses might need to be adjusted for this novel coronavirus, with some arguing that because of the threat of ventilator-induced lung injury, “putting patients on ventilators for Covid-19 pneumonitis could be a bridge to nowhere”.
In treating any critically unwell Covid-19 patient, we need to respond to the patient’s pathophysiology, not apply protocols blindly. There is no magic bullet in any of this, and the best way to manage this is to pay strict attention to detail, provide excellent organ support, as well as excellent nursing care and physiotherapy, and that is about as much as we can do. Everyday sees new research findings emerge, with an updating of guidance.
The medical community is working on overdrive to develop a vaccine for this dreadful disease, with one vaccine trial in Russia and two in China, in addition to repurposing other existing medications and developing other newer ones by way of gold-standard clinical trials. Quarantine and social distancing remain the only practical ways of dealing with it.
Mutamba is a UK-based ophthalmic and oculoplastics surgeon, with a passionate interest in Zimbabwe. He works as a consultant in the UK. His credentials are as follows: BSc Hons (UZ), MBChB Hons (UZ), MSc (Lon), DTM&H (Lon), MRCP (UK), FRCOphth (UK).