SARS-CoV-2: an unknown virus with a high degree of contagiousness, mistaken for a trivial flu, that is capable of triggering a tsunami of reactions in the human body. Few certainties and many hypotheses. But above all, what will actually cure it?
Effectively treating COVID-19, the disease that develops following coronavirus infection, has proven to be a very difficult task right from the start, and which has quickly led to the collapse of many hospitals around the world.
The reason therein lies in the fact that SARS-CoV-2 is a new coronavirus, and therefore there are no known and proven drugs or treatments of any kind. In this scenario of increasing uncertainty, Doctors and Researchers have attempted to use drugs already used against other viruses — but with discouraging results.
What treatments are available today?
We can divide treatments into five categories; it’s important to point out that studies on the efficacy of drugs are still in progress and are updated on the website of the Agenzia Italiana del Farmaco (AIFA). We should mention the following:
- Antiviral drugs
- Plasma and therapeutic antibodies
- Inhibitors of inflammation
- Supporting therapies
Let’s analyze them one-by-one, trying to understand their use, availability and effectiveness.
They are a category of drugs that act directly on the virus, preventing its replication. Some drugs already used to treat HIV (and which inhibit viral replication) are used as part of the (Italian) national emergency management plan. In general, their use is directed toward COVID-19 patients with lower severity and in the early stages of the disease.
Chloroquine and hydroxychloroquine (trade name of the drug Plaquenil) have also shown some efficacy; although studies conducted by various research groups have led to different efficacy results. Chloroquine and hydroxychloroquine act by preventing the virus from entering the cell and thus preventing the replication and spread of SARS-CoV-2. Currently, the use of Plaquenil is recommended — both in less severely-affected COVID-19 patients managed at home and in hospitals, as is specified by AIFA.
Remdesivir, the first COVID-19 drug approved by the Federal Drug Administration (FDA), deserves special mention. This drug prevents the replication of the virus, and therefore its propagation to other cells of the patient. It’s been tested on more than one thousand patients, it reduces the time needed for recovery by 30% and has also reduced the overall number of deaths. AIFA has also approved the use of Remdesivir in ten specialized centers, located throughout Italy.
Plasma and therapeutic antibodies
Following a venous sampling from a donor, the blood is centrifuged, in order to separate the cells and thus obtain the plasma, which is the liquid part of the blood and has a unique yellowish color. The technique is called plasmapheresis and has been known for many years — and has proven effective in the treatment of Rabies, Hepatitis A, Hepatitis B, but has neither worked with Hepatitis C nor HIV.
Plasma contains water, proteins, nutrients, hormones and antibodies which are the important part of an anti-COVID-19 therapy. The use of plasma as a cure is not comparable to a simple transfusion, since plasma must be treated in order to be used in patients. In fact, it’s necessary that the plasma donor has recovered from COVID-19 and has undergone at least two swabs that have certified the recovery.
In addition, plasma is not without risks; in fact, it must be verified that there are no other infectious agents such as Hepatitis A, B, C, HIV, Parvovirus B-19; tests that have a cost. Only after these controls, and having verified that there is a sufficient number of neutralizing antibodies (those useful for the immune response), the treated plasma can then be administered to the patient and therefore be called hyperimmune plasma. We must also stress that treatment with plasma doesn’t protect the recipient forever, since it doesn’t stimulate the production of antibodies, but provides them, and therefore the supply of these antibodies will eventually become exhausted.
Therefore, the treatment with hyperimmune plasma is not free and not even risk-free; its effectiveness has been proven in some hospitals in Italy (namely, in Pavia and Mantua) but must be confirmed by rigorous scientific studies and on an adequate number of patients.
Since many donors are needed for the treatment of patients and not all former COVID-19 patients have a sufficient number of neutralizing antibodies, Researchers are studying the possibility of producing immunoglobulins (i.e. therapeutic antibodies). These studies are directed toward the production of an artificial serum, containing human antibodies directed to the spike protein present on the surface of SARS-CoV-2. The advantage would be a standardized process of production of the treatment, in sufficient quantity for all patients — and available at a reasonable cost.
Inhibitors of inflammation
It’s now well established that SARS-CoV-2, in addition to the ability to develop into interstitial pneumonia, is able to cause an altered inflammatory response that in some patients, causes a “cytokine storm” that precipitates so-called systemic damage (i.e. to many organs).
Thanks to the studies conducted at the Istituto Pascale di Napoli (Pascale Institute in Naples), the experimentation with Tocilizumab, an anti-arthritis drug, has been authorized by AIFA. Tocilizumab is used in cancer patients to counteract the effects of immunotherapies, such as excessive cytokine production; exactly what happens in COVID-19 patients in the severe stages. Inflammation in the pulmonary alveoli makes gas exchange difficult; Tocilizumab reduces inflammation and therefore improves breathing. This drug (as well as other similar drugs) does not act on the virus but on the effects of the infection.
As previously mentioned, the altered inflammatory response of COVID-19 patients is at the root of the “cytokine storm” and consequently the possibility of thrombosis (i.e. clots that obstruct the passage of blood) and can cause the death of the patient. For this reason and thanks to preliminary scientific studies, AIFA has included low molecular weight heparin among the drugs that have been cleared to be used in the treatment of COVID-19 patients.
Low molecular weight heparin is already used in post-surgical venous thromboembolism prophylaxis, and also in venous thromboembolism in patients suffering from acute diseases such as heart and respiratory failure.
In COVID-19 patients, low molecular weight heparin is now administered under strict medical supervision because it can lead to bleeding, but can be administered in the early stages of the disease as a prophylaxis for venous thromboembolism, due to enticement. Or, even in the more advanced phases, in order to contain the thrombotic phenomena that can arise from the pulmonary circulation — as a result of excessive inflammation.
Supporting therapies are non-pharmacological therapies such as oxygen therapy, non-invasive positive-pressure ventilation, and mechanical ventilation by intubation. In extreme cases, a Doctor may decide for Extracorporeal Membrane Oxygenation (ECMO), which consists of replacing the pulmonary process with an external machine that increases the oxygenation of the blood.
How close are we to a vaccine?
In conclusion, much progress has been made since we first encountered SARS-CoV-2, but there’s still a long way to go in fully understanding the biology of the virus — and to develop effective drugs, and possibly even a vaccine.
This post is also available in: Italiano