As we reflect on 2021, many countries including US, UK and Europe have experienced another large wave of infections in the last few weeks of 2021, once again stressing their healthcare system. For many countries, the number of COVID19 infections in 2021 far exceeded the 2020 figures. Many countries have also re-instated “lockdown”, curtailed social activities, reduced opening hours of food and beverage establishments, decreased capacity at entertainment venues and “closed” their borders.
In 2021, we made remarkable progress in disease prevention with rollout of population wide COVID19 vaccinations. At last count, almost 8.8 billion doses of COVID19 vaccines (in various formulations) have been administered to the global population. We now have active intervention in treating patients, especially in the earlier stage of their infection with anti-viral agents and monoclonal antibodies.
What went wrong?
The Omicron strain emerged and was first reported by South Africa. It was quickly designated a “variant of concern” by WHO on November 26th 2021. Based on the >50 mutations detected (of which 30 were in the spike protein involving the receptor binding domain) in the Omicron strain, scientists expressed grave concern that this new strain would be more transmissible, bypass vaccine induced immunity from our current vaccine formulations and that it would start off another wave of infections.
These fears were rapidly realised. By late December 2021, the omicron strain became a co-dominant or the dominant strain in US, UK and many countries in Africa. This also coincided with marked increases in COVID19 infections in these countries and also in Europe. The Omicron variant has now been identified in >110 countries by the end of December 2021. In response, many countries have re-imposed face coverings (indoors and in some cases, outdoors), reduced social interactions, restrictions in dining for food and beverage establishments and in some instances, closure of entertainment venues. In the last 2 weeks of December, large sporting events and year end celebrations were curtailed or cancelled completely.
More transmissible but maybe less risk for hospitalisations
The Omicron strain is indeed highly transmissible and its replication rate is faster and Ro (replication number) is also higher than the Delta strain. This explains its rapid emergence as the dominant strain in many countries and there is no good reason why it will NOT become the dominant global strain by early 2022.
The encouraging real world data is as follows: A University of Edinburgh study reported that patients infected with the Omicron strain in Scotland were 67% less likely to require hospitalization. A study by Imperial College on a larger pool of UK patients reported a 50-70% reduction in hospitalisations for those infected with Omicron compared with the Delta strain. Similarly, South Africa reported that patients infected with the Omicron strain were 80% less likely to require hospitalisation and that the Omicron wave may result in a short intense spike of cases. COVID19 cases have been steadily decreasing in South Arica by the end of December 2021, just one month after it was reported there. The caveat is that a small percentage of hospitalizations of a larger number of cases is still a large number that may still overwhelm the hospital system. In addition, a large number of cases will result in a sizeable population being on medical leave and isolation resulting in disruption of economic activity.
There may be a scientific basis to these observations. Research from HK University School of Public Health used an ex vivo model and demonstrated that the novel Omcrion strain had higher replicative capacity (up to 70 times at 24hours) in bronchial (upper airway) cell culture compared with the Delta strain but lower replicative efficiency and fusion in alveolar (lung) cell cultures compared with the original SARS CoV2 virus.
What’s next after Omicron?
Variants such as Omicron and Delta developed mutations that blunt the potency of antibodies raised against previous versions of SARS CoV2. How the virus evolves over the next few months and years will determine what the end of this global crisis looks like.
Scientists expect the virus to eventually evolve more “predictably” and behave like other respiratory viruses. When this will happen is anyone’s guess.
In 2022, we can expect that the Omicron strain will dominate globally and new strains are likely to emerge.
Keep on Jabbing!
The public health data for the COVID19 pandemic is that adults will need at least 3 doses of vaccination to reduce the risk of severe disease in response to deal with emerging strains of 2021 such as delta and Omicron.
It is increasingly appreciated that severe COVID19 will evolve into a disease of the unvaccinated or inadequately vaccinated.
Further tweaks of the current vaccines will be necessary. In the meanwhile, the only defence is boosting those who have received 2 doses of vaccination. In Israel, in the midst of the Delta wave, a 3rd dose of vaccine reduced infection rate by 10 fold and mortality by 90% .
Israel had initially announced on December 21st, 2021 that to “battle the Omicron strain”, it will start administering a 4th dose of mRNA vaccine to persons aged 60 years and above. UK and several countries are considering the same. In the latest announcement, the 4th dose or second booster COVID19 vaccine will be on a clinical trial in an Israeli hospital and not rolled out nationwide.
The critical issue is the use of finite resources. Do you focus on giving the 4th dose to the previously vaccinated or make the effort to vaccinate the unvaccinated?
In Singapore, there are plans to roll out 2 million more doses of vaccination in the first few months of 2022. The target population for these 2 million doses are as follows: booster does for eligible adults (by 25/12/21, 87% have received 2 doses but only 36% have received their booster dose), teenagers and children between ages 5 to 11 years.
Paediatric COVID19 vaccines
The Pfizer BioNTech vaccine was approved for use in children aged 5-11 years in the US at the end of October 2021. Similarly, numerous the countries including Singapore have also approved the paediatric formulation. The benefits of paediatric vaccination are as follows
- Protect children from severe disease
- Decrease spread to family and community
- Ensure educational continuity
In the US, the take up has been about 1/3 eligible children have take at least 1 dose of the padeiatric formulation. Others have either adopted a “ wait and see” approach or rejected vaccinating their children outright. In Singapore, it was reported that 40% of eligible children aged 5-11 years were signed up to undergo COVID19 vaccination.
Do we need new COVID19 vaccines?
Variants such as Omicron and Delta developed mutations that blunt the potency of antibodies raised by our current vaccine formulations and also by infection induced immunity against the earlier strains of SARS CoV2. In a recent report, 3 doses or MRNA COVID19 vaccines provided around 60-70% protection against infection by the Omicron strain.
Research to find further solutions are ongoing. WHO has reported that there are more than 300 candidate vaccines in various stages of development.
There has been increase in travel and social interactions during the recent year end holidays and it is not clear if this was due to increased confidence in vaccines or just pandemic fatigue
Omicron Parties: Should we just get infected and be done with it?
There is a school of thought that “natural” infection with Omicron will provide a super-boost to your immunity rather than queue for a third or fourth (booster) dose of COVID19 vaccine.
In a study from Denmark reported in Eurosurveillance, within 1.5 weeks of identifying the first case of Omicron on November 28th 2021, there were >700 infected with Omicron and there was widespread community transmission despite the country imposing travel restrictions on numerous African countries since November 27th 2021. The major driver of this was thought to be a large party involving young adults resulting in a superspreader event. A similar superspreading event was also reported in a company Christmas dinner in Oslo Norway. Many of the Omicron infections in Europe were mild and did not require hospitalisation.
After 2 years of lockdown alternating with respite, month after month of surges and waning of cases, it may be inevitable that infection with SARS CoV2 for most individuals will occur.
This unconventional and somewhat radical approach is as follows: The Omicron strain being more transmissible but with less disease severity may be the ideal “natural booster” to young persons who had already received 2 doses of COVID19 vaccination. Such an approach is not likely to be endorsed publicly by any government body.
By the end of 2021, there were an estimated 285 million cases of COVID19 infection with 5.4 million deaths. We are only just beginning to learn about the later consequences of COVID infection, the “postacute-COVID condition” and often termed as “long COVID”.
Long COVID is the umbrella term for a wide range of physical and mental consequences experienced by some patients after infection by the virus, SARS-CoV2. It relates to the condition that is present at least 4 weeks after the acute phase of the SARS CoV2 infection. The frequency varies considerably in the medical literature and ranges from 5% to 80%. It may also affect persons who had asymptomatic or mildly symptomatic SARS CoV2 infection.
Th long COVID symptoms may last weeks to months and may be:
- Continuing or persistent symptoms that started from the onset of the infection
- Recurrent symptoms which wax and wane in severity
- New symptoms which were not present during the acute illness
Multiple onset patterns have been described and some of them share similarities with other post-viral syndromes, post-severe pneumonia (from whatever aetiology), chronic fatigue syndrome, dysautonomia, orthostatic intolerance like POTS, mast cell activation syndrome etc.
Long COVID is a heterogenous condition that we are just beginning to learn about and it is likely the symptoms are due to different underlying disease mechanisms including:
- Organ damage from acute infection
- Complications from persistent hyperinflammatory state
- Ongoing viral activity from the host reservoir
- Inadequate antibody response to SARS CoV2
The first articles on long covid were published in the second half of 2020 and there have been many more. WHO has also recognised that Long Covid may pose a potential health problem in the coming years and has convened several meetings on this condition. Several countries and medical associations have also issued guidelines on assessment and management of long COVID.
What else can we do to help to reduce our risk for COVID19 Infection?
Whether it is delta, omicron or another new unknown emerging SARS CoV2 strain, non-Pharmaceutical Interventions such as face coverings, social distancing and good hand hygiene continue to provide an additional layer of protection against COVID19 infection.
We can re-imagine our work and living environment; in essence, we need to make indoors more like outdoors – improving ventilation is probably something that has been under-utilized
Outpatient treatment: Believe it or not?
Nirmatrelvir boosted with ritonavir (Paxlovid), received emergency use authorisation (EUA) by the US FDA just before Christmas 2021. It is a protease inhibitor that has in vitro activity against all SARS CoV2 variants to date. It reduced rates of hospitalization and all cause mortality by almost 90%. The study population were unvaccinated high risk adults who had mild to moderate COVID19 infection within 3 days of symptom onset. No specific adverse effects are known at this time. Under the EUA, the drug has been authorised for use in unvaccinated persons above the age of 12 years. It is a 5 day course of oral medications.
Molnupiravir (Lagevrio) also received EUA in the US in late December 2021. The drug acts by causing fatal mutations in the SARS CoV2 and it too has in vitro activity against all SARS CoV2 variants to date. It reduced rates of hospitalization and all cause mortality by 30%. The study population was similar. i.e. unvaccinated high risk adults who had mild to moderate COVID19 infection within 5 days of symptom onset. There are concerns about mutagenicity, bone and cartilage toxicity of the drug and it is not approved for use in pregnant women and persons younger than 18 years. The course is 4 capsules twice daily for 5 days.
Remdesivir (Veklury): Intravenous remdesivir has been used in hospitalised patients with severe COVID19 infection requiring oxygen therapy since mid 2020. In a trial published in December 2021, intravenous remdesivir was administered in nonhospitalised patients who were at high risk for COVID19 progression. A 3 day course had minimal adverse effects and was associated with a 87% reduction in hospitalisation and death.
Tixigevimab with cilgavimab (Evusheld) – These 2 long acting combination monoclonal antibodies when administered will help to prevent COVID19 infection. It is called pre-exposure prophylaxis and prevents infection before contact with the virus. In the PROVENT trial, Evusheld had 83% efficacy for 6 months at preventing COVID19 infection when compared to placebo. It is approved for use in the US for patients who are immunocompromised and for those who had severe adverse reactions to vaccinations.
While the outpatient treatments described above are anticipated to become essential tools in the management of COVID19 infections in 2022, it is important to reiterate that vaccination remains as the most important public health tool in controlling the pandemic.
We had to battle with misinformation about COVID19 since the onset but 2021 was particularly bad because of the global rollout of vaccinations. The anti-vaxxers wrecked havoc and they have continued “ammunition” because we had wave after wave of infections in 2021 with the need for booster vaccinations (a third dose and now a fourth dose is being explored).
For the specialists in our group, we are advocates of vaccination but remain respectful and honour our patients’ ability to make choices for their health. We will not abdicate our role to be a source of medical expertise.
As we enter the third year of the COVID19 pandemic, are we going to continue lurching from crisis to crisis or will we finally bring the virus under control? The pieces of the puzzle are indeed falling into place, we are optimistic and remain hopeful that 2022 will be the turning point in our fight against SARS CoV2. To a great 2022