Following an outbreak of cases of a serious illness in Wuhan, China in December 2019, the cause of the illness was confirmed as a novel coronavirus and the number of cases and deaths have soared as people have moved around our connected globe.
A range of human coronaviruses (HCoV) already cause 15-30% of common colds. However, notable outbreaks have resulted from some coronaviruses moving from animal reservoirs to humans, including the SARS-CoV (2002, from bats in China) and MERS-CoV (2012, from camels in the Middle East) outbreaks. These so-called ‘zoonotic’ (animal origin) viruses tend to cause a more serious lung infection that may result in adult respiratory distress syndrome and death. The source of COVID-19 is not known but so far, the risk of dying from an infection is thought to be significantly lower (a figure of 3.8% has been quoted but thus far testing has been sporadic) than that of SARS-CoV (10%) and MERS-CoV (37%).
However, certain people appear to be more vulnerable to a more severe infection by COVID-19, such as older age groups and people with pre-existing health problems such as asthma and other lung diseases, as well as those whose immune systems are suppressed. It is not yet understood how suppressed immunity influences the risk from COVID-19 infection – until more is known, shielding is strongly advised.
The structure of COVID-19
Coronaviruses are basically strands of RNA (genetic material similar to DNA) in an envelope. In order to reproduce, they need to enter a host cell (in the respiratory tract in the case of coronaviruses) and in doing so, they induce the host cell to produce more copies of themselves along with various proteins that help the virus machinery to function. Along with this, the host’s immune system kicks into action and tries to resist the invasion. In most cases, this resistance is successful and the individual develops immunity to the virus. It remains to be seen whether this immunity is long-lasting enough to prevent further infections.
The RNA structure of the virus can be dissected so as to understand exactly what it consists of (the genomic sequence). This was identified by scientists in China and released to public databases in January 2020 so as to kick-start a research effort in testing and therapy.
Using the identity of COVID-19 against the virus
To test if you have COVID-19: the first available test is based on the detection of the COVID-19 RNA in respiratory (nose, throat and lung) secretions. This is a specific test as it looks for COVID-19 but its sensitivity (the number of true cases identified) needs improvement. Also, such a test can only be done in specialist laboratories and is therefore not widely available.
In most cases of infection, evidence for this can be found by looking for antibodies in the blood (produced by the person’s immune system in response to the infection). This test is not yet available but when it is, the testing process will be more widely available and easily performed.
Antiviral medication: Nucleoside analogues
There already exist several treatments for viral infections including aciclovir for the virus that causes shingles, various combinations to treat HIV and some agents to treat types of viral hepatitis and influenza. One group of these are the so-called nucleoside analogues, which are basically chemicals that mimic components that make up DNA and RNA. These chemicals interfere with the production of more DNA or RNA (which is essential for the reproduction of the virus), leading to the death of the virus. At present the most promising agent in the coronavirus setting is remdesivir and clinical trials are already underway in people affected by COVID-19. Treatments are being tested in patients with different severities of COVID-19 infection either alone or in combination with other agents that modulate the immune response to the infection.
Teaching an old dog new tricks: chloroquine
This is an age-old drug that has been used to treat malaria for decades following its discovery in 1934. It also has antiviral properties - it is thought to impair the release of the virus’ genetic material into the host cells resulting in its inability to replicate. Trials are underway to test its usefulness in treating COVID-19 infection. Although cheap and widely available, it has a range of potential side effects such as eye damage, deafness and tinnitus, mental and mood changes and heart rhythm disturbances. Consequently, it needs to be tested so as not to cause more problems than it solves in COVID-19 patients as well as to see just how effective it is in treating COVID-19 infection.
Repurposing drugs: protease inhibitors
In order for COVID-19 and other viruses to replicate, certain enabling protein structures are modified by the virus to make this happen. So-called protease inhibitors prevent this from happening and this results in anti-viral action. Such drugs are already widely used to treat HIV and appear to have activity against SARS and MERS. Trials of such drugs are also underway in COVID-19 patients.
Repurposing drugs: other inhibitors
Other targeted therapies such as BTK inhibitors (such as ibrutinib, acalabrutinib and zanubrutinib) and other so-called kinase inhibitors (such as ruxolitinib) are being tested in the COVID-19 setting to see if they modulate the body’s immune response to COVID-19. These studies are in current rapid set-up in hospitals around the world (including in the UK).
Vaccines are the most effective strategy for preventing infections and many vaccines are in use today for a variety of diseases. At present, there is no vaccine for human coronaviruses. Research groups around the world are accelerating the development of COVID-19 vaccines using various approaches. Despite the massive expansion in understanding of immune responses to infection, research is often hindered by a lack of understanding of the exact kind of immune responses required for protection, or by a lack of approved methods of administration or additional ingredients needed to stimulate the immune system safely.
Usually, the development of a vaccine requires testing in the laboratory in so-called ‘cell lines’ (test tube experiments) then animal models, and then humans. This ensures the vaccine is perfected in terms of effectiveness and safety before it is launched into standard practice.
These steps typically take years and require a massive and sustained investment and effort by pharmaceutical companies and research laboratories. In addition, even if a viral target is identified, this might need updating due to mutations (spontaneous variations in the virus genes) which the virus undergoes to overcome the vaccine.
Currently, a trial developed at the University of Oxford by the Jenner Institute and Oxford Vaccine Group is underway with UK Government backing, starting in younger persons (who are more tolerant of possible side effects) before moving to other age groups. There is an estimate of a possible workable vaccine in September 2020. WMUK will update the website as more information becomes available.
Until an effective antidote to Covid-19 is available, it remains imperative that persons who are in the highly vulnerable groups remain in strict isolation and follow NHS guidance.