Kingston Mills: Is Covid gone or will dangers keep lurking?

Effect of new mutations on transmission, immunity and severity difficult to predict

Everyone desperately wants the Covid-19 pandemic to end so that we can return to our normal lives and no longer have to endure restrictions and daily headlines about case numbers.

The fear of being infected, hospitalised or possibly dying from Covid-19 persists for individuals at high risk of developing severe disease. So, when will it all be over?

It has been suggested that Omicron, the Sars-CoV-2 variant that has caused the recent global eruption of cases, may end the pandemic. The World Health Organisation and medical experts, including Tony Fauci, have warned that we need to be more cautious in making these predictions. So, what does the science say?

In all my years of scientific research, including work on the effect of virus mutations on immune responses to influenza or human immunodeficiency virus (HIV) at the National Institute of Medical Research in London, I have never seen mutations in an individual virus variant to the extent of those in Omicron.

It has over 30 mutations in the spike protein, many in the region that binds to receptors on the human cells that it infects. Mutations can enhance virus infectivity, but also reduce the effect of neutralising antibodies that protect us against the infection. From the perspective of the virus it is an advantage to have mutations that do both.

There are three possible consequences of the mutational changes that occurred in Omicron: 1. The virus could become more pathogenic, ie, cause more severe disease. This does not appear to be the case and perhaps the opposite is true. 2. The virus could evade immunity induced by vaccines or previous infection. The evidence for this is incontrovertible. 3. The virus could be more transmissible. The evidence for this is very strong.

Respiratory tract

Lab studies have shown that mutations in the spike protein of the Omicron variant enable the virus to bind more tightly to the tissues of the respiratory tract, especially the nose, suggesting that, when compared with other Sars-CoV-2 variants, Omicron infects the nasal tissues more readily than the lungs. This, in turn, is consistent with clinical reports that Omicron causes a milder, predominantly upper respiratory tract infection; this contrasts with the severe lung infection seen with earlier variants that was associated with local and systemic inflammation, which can lead to sometimes fatal disease.

Omicron is associated with less severe disease because of the high level of immunity in the population induced by vaccines and/or previous infection

It can also be argued that rather than causing milder disease, Omicron is associated with less severe disease because of the high level of immunity in the population induced by vaccines and/or previous infection. Neutralising antibodies induced with Covid-19 vaccines or prior infection with other variants of Sars-CoV-2, while not preventing infection with Omicron, can reduce the viral load. Furthermore, vaccines also mobilise cells of our immune system, called T cells, that kill virus-infected cells and produce natural antiviral molecules; these can limit the infection but do not prevent it.

In Ireland, while 77 per cent of the entire population have received two doses of a Covid-19 vaccine (or one dose of the Janssen vaccine), only 51 per cent have received a booster dose. A recent study from the UK has shown that two vaccine doses confer only limited protection against symptomatic Covid-19 caused by Omicron. In contrast, vaccine effectiveness against symptomatic disease was 65-75 per cent after a booster dose with an mRNA vaccine, but this waned to 40-50 per cent after 10 weeks. However, three vaccine doses were 83-92 per cent effective at preventing hospitalisations.

The high case numbers in Ireland are consistent with the international evidence that two doses of Covid-19 vaccine, while protecting against severe disease, provide limited protection against symptomatic infection with Omicron. Ironically, the upside of the high case numbers is that a combination of vaccination and Omicron infections should confer a good level of protection in the population.

Immune response

Current vaccines induce antibodies that are highly effective at neutralising the Wuhan strain and early variants of the virus, but are much less effective against Omicron, whereas infection with Omicron will induce protective antibodies against Omicron. So, priming the immune response with vaccines, and “boosting” by infection with Omicron, should confer effective immunity against Omicron or minor variants thereof.

Those that have not been infected with Omicron will need to be boosted with an Omicron-specific vaccine, which have already been developed by the vaccine manufactures and should be available in late March or April.

The recent fall in case numbers in Ireland and, more importantly, the stabilisation of hospital and ICU admissions with Covid-19 is very encouraging and the numbers should continue to fall significantly in the coming weeks. However, unvaccinated individuals and people with underlying medical conditions or on immunosuppressive therapies are still at high risk of developing severe Covid-19 that could result in hospitalisation and ICU admission if infected with Omicron.

Unvaccinated individuals and people with underlying medical conditions or on immunosuppressive therapies are still at high risk of developing severe Covid-19

It is also worth reflecting on the chilling statistics from the WHO that, in the week January 10th-16th, 2022, there were 18 million new cases and 45,000 deaths from Covid-19 globally, so the epidemic is not over yet.

In Ireland, it would be prudent to retain measures that minimise transmission of the virus in the population until hospital admission with Covid-19 has reduced to low levels. The use of Covid certificates based on three vaccine doses, or two doses and recovery from Omicron infection, would ensure a safer full return to hospitality, entertainment and sporting events, and would encourage uptake of booster vaccines. When applied to international travel, they would also prevent further importation of Sars-CoV-2 from countries that still have high circulating levels of the virus. The argument for vaccine equity for developing countries, where vaccine coverage is still shocking low, is stronger than ever. The pandemic will never be over until all countries have equal access to vaccines.

Mutation emergence

The biggest cloud on the horizon is the emergence of new variants that are as transmissible as Omicron but completely escape immunity induced by the current vaccines. There is a strong possibility that further Sars-CoV-2 variants will emerge, but it is impossible to predict when, and what effect the next mutations will have on transmission, immunity and disease severity. If new variants are minimally different from Omicron, then an Omicron-specific vaccine or a previous infection with Omicron in vaccinated individuals should still confer protective immunity.

The orally administered antiviral drugs, Pfizer’s Paxlovid and Merck’s Molnupiravir, that suppress replication of Sars-CoV-2 and significantly reduce hospital admission and death in high-risk individuals, together with Xevudy (Sotrovimab), an injectable virus-neutralising antibody from GlaxoSmithKline, should soon be available in Ireland. These are important new weapons in the fight against Covid-19, but only for selected individuals at high risk of developing severe disease.

Vaccines will continue to be the key long-term approach for preventing infection with Sars-CoV-2. Scientists are working on new vaccines that induce better immunological memory, which will sustain their protective effects without the need for repeated booster doses. Covid-19 vaccines are also being developed that should completely prevent infection of the nasal cavity as well as the lungs and thereby prevent transmission of the virus. With global access, these next-generation vaccines could mitigate new virus variants, which is the biggest threat in the future direction of this pandemic.

Kingston Mills is professor of experimental immunology and academic director of the Trinity Biomedical Sciences Institute, Trinity College Dublin