Omicron leads to milder disease compared to the Delta variant

Omicron leads to milder disease compared to the Delta variant

Macron said “I am not about pissing off the French people. But as for the non-vaccinated, I really want to piss them off. And we will continue to do this, to the end. This is the strategy. In a democracy, the worst enemies are lies and stupidity. We are putting pressure on the unvaccinated by limiting, as much as possible, their access to activities in social life.” I was surprised Djokovic was given an exemption to play in the Australian open unvaccinated. I note Rio has cancelled its carnival for a second year in a row. A fourth dose of vaccine boosts antibodies five-fold a week after the shot is administered, the Israeli prime minister, Naftali Bennett, said, citing preliminary findings of an Israeli study.

As the Omicron variant collided with the holiday season, daily cases in the UK surpassed 200k and weekly new case numbers in the United States rose dramatically to 2.64 million over the most recent week, increased by 193% from two weeks prior and eclipsing prior new case peaks. For comparison, the current US week’s cases are 2.3 times greater than the peak weekly cases of 1.14 million observed in the Delta wave in summer 2021 and are 1.7 times greater than the 1.53 million peak weekly cases observed during the winter 2020/2021 wave, which occurred before the widespread rollout of vaccines. Examining regions across the United States, compared to two weeks prior, new cases are increasing dramatically, with 55%, 196%, 222%, and 360% increases compared to two weeks prior in the Midwest, Northeast, West, and South, respectively. The US is already leading the hospitalisation wave:

The silver lining in the current wave is the suspected decreased severity of illness. However, the sheer number of infections and the still-large number of unvaccinated individuals in the United States (62% of population fully vaccinated) are concerning. Over the week, 7,906 new deaths were recorded, increased slightly (1% decline) from the week prior and down slightly (4% decline) from two weeks prior. While one can be optimistic that hospitalisations would not trend upward as rapidly in the current wave as new cases, this week the number of hospitalisations did increase significantly by 41% compared to two weeks prior and is now 97,218. Breaking down hospitalisations by region, compared to two weeks prior, they increased by 17% and 28% in the Midwest and West, respectively, but rose dramatically by 51% and 71% in the Northeast and South, respectively:

I also note, according to the latest data from the CDC, as of the week ending December 25, Delta still composed 41.1% of all U.S. COVID-19 cases (Omicron composed 58.6%); therefore, many of the hospitalisations observed are likely driven by Delta infections, although the current proportions remain unknown. While deaths remain flat compared to prior weeks, with the large increase in hospitalisations, increases in deaths are likely. Currently, 3,314 pediatric patients are hospitalized with COVID-19, up 92% from two weeks prior. Pediatric hospitalisations are now at a pandemic peak, exceeding the prior peak of 2,561 patients in the hospital on September 1, 2021. When it comes to ‘kids’, independent experts who advise the CDC on vaccination policy will meet today to discuss yesterday’s move by the FDA to extend emergency use authorisation for the Pfizer-BioNTech Covid-19 booster shot to include teens aged 12 to 15. It’s possible the panel will issue a "permissive recommendation," saying these youths may get a booster if they wish, but stopping short of urging them to do so. If the committee goes this route, it will likely be because of outstanding questions about the risk of myocarditis and pericarditis — inflammation of the heart and tissue surrounding the heart, respectively — that may be associated with a booster in this age group. The ACIP’s guidance must be approved by CDC Director Rochelle Walensky before it can come into effect:

With new cases rising throughout the United States, another winter wave of COVID-19 is underway, driven by a mix of seasonality, overall fatigue with nonpharmaceutical interventions (such as less distancing, especially around the holidays), waning vaccine immunity (leading to more mild/moderate disease), and the spread of Omicron. While the prior winter wave of COVID-19 proved the deadliest to date, spread of the highly transmissible Omicron and fatigue with nonpharmaceutical interventions is pushing the current wave to be by far the largest yet, at least in terms of new infections. I believe hospitalisation trends, despite being a lagging indicator, will be a more informative indicator of COVID-19 dynamics in the United States considering the rate of vaccination, which will reduce risk of hospitalisation, and the potential for Omicron infections to be milder. Despite a lower-flow-through to hospitalisations, however, with cases rapidly increasing and new cases already at numbers far exceeding prior waves of COVID-19 (not including a lack of reporting of at-home tests, which is masking the true number of positive cases, potentially by several-fold), I believe with a large number of hospitalisations expected in coming weeks, healthcare systems are likely to be strained.

Commercially, for anyone who’s been following how the US government has been allocating and shipping supplies of its Covid-19 treatments over the past year, the news has shifted so many times that it can be difficult to keep track of what’s still being shipped and where. More change is coming this week too, as HHS has now decided to re-start shipments of Lilly (bamlanivimab plus etesevimab) and Regeneron (casirivimab plus imdevimab) monoclonal antibody products after a short pause because neither product works against the new variant Omicron. Lilly’s combo also was halted last June due to the presence of other variants. “If the Delta VOC [variant of concern] still represents a significant proportion of infections in a region and other options are not available or are contraindicated, eligible patients can be offered bamlanivimab plus etesevimab or casirivimab plus imdevimab, with the understanding that these treatments would be ineffective if the patients are infected with the Omicron VOC,” HHS’ ASPR said in a statement.

So, Omicron leads to milder disease compared to the Delta variant (67-73% lower risk of severe disease), which is more likely to manifest in the nose and throat as opposed to in the lungs. Omicron's enhanced ability to cause re-infections and greater transmissibility means that extrapolating underlying Omicron infection rates into acquired immunity levels will become important over time, especially for countries pursuing zero-COVID or more restrictive social policies. Gauteng COVID-19 cases peaked 9 December 2021 at 897% of Delta wave (7-day moving average), hospital admissions 39% of Delta wave, deaths at 13% of Delta wave:

However, in the near-term, all the focus is on whether Omicron infection waves will follow a similar pattern to that seen in South Africa where daily cases peaked within ~4 weeks before declining sharply. Healthcare systems are under pressure in the UK as hospitals aim to maintain urgent and high priority elective care activity. The situation is distinctly different from January 2021, reflecting ~60% fewer patients in critical care for COVID-19 respiratory problems, with the key challenges being a combination of: i) staff absences, which could become as high as 25%, and ii) having to isolate Omicron patients, whether incidental or not, to avoid cross infection. This is London COVID-19 dynamics relative to January 2021 peak (lhs) and 7-day average week over week changes (rhs):

With the holiday period introducing volatility into the tracking data, the focus is on whether UK Omicron cases in leading-indicator London will continue to decline from the recent 23 December 2021 peak or begin to rise again, with COVID-19 hospital admissions lagging by about a week. London can be used as a primary focus as a proxy for other regions of the UK (it appears to be 10-14 days ahead) and other Northern Hemisphere countries going through winter respiratory infection seasons. Projected Omicron cases and hospital bed occupancy in London:

At this stage, London appears to be following a similar trajectory as Gauteng, South Africa, but the picture will become clearer over the next two weeks as the potential impact of New Years celebrations, inter-generational mixing and the return of schools take effect. The UK government has indicated that further COVID restrictions are unlikely to be introduced based on the current data, with the potential that hospital admissions in London may have peaked. COVID-19 patients admitted to hospital in London:

Whilst vaccine effectiveness against hospitalisation is estimated to be 88% for Omicron after 3 doses, efficacy against symptomatic infection with Omicron wanes significantly to ~40-50% after 10 weeks. Updating our projections for vaccine efficacy and recent hospital dynamics where 33% of COVID-19 admissions are "incidental", one can easily project ~120,000 COVID-19 hospital admissions over the Omicron plus Delta wave period and peak hospital cases of ~21,000 (compared to 39,254 at the January 2021 peak).

The clinical severity of COVID-19 patients admitted to hospitals in Gauteng, South Africa, during the Omicron wave has been compared to previous waves by Jassat and his team. There were 41,046, 33,423, and 133,551 SARS-CoV-2 cases in the Beta, Delta and Omicron waves, respectively. An estimated 4.9% of cases were admitted to hospital during the Omicron wave compared to 18.9% and 13.7% during the Beta and Delta waves (64% lower risk of hospitalisation in the Omicron wave versus the Delta wave). In terms of disease severity, an estimated 28.8% of admissions in the Omicron wave were for severe disease compared to 60.1% and 66.9% in the Beta and Delta waves (73% lower risk of severe disease in the Omicron wave versus the Delta wave).

They concluded that any combination of a less-virulent virus, co-morbidities, high immunity from prior infection(s) or vaccination may be important contributors to these observations and therefore care should be taken in extrapolating this to other populations. Omicron is better at infecting those with vaccine or natural immunity compared to Delta and breakthroughs/re-infections are less likely to lead to severe disease. Some have argued that much of the reduction in observed severity is due to intrinsically lower virulence, with an abrupt drop in the case fatality ratio in South Africa from 3% in late November to 0.36% during the Omicron wave in essentially the same population. Omicron disease severity and risk of hospitalisation compared to Delta:

https://www.medrxiv.org/content/10.1101/2021.12.21.21268116v1; https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf

These observations are supported by studies in S Africa, England, Scotland and Ontario as well as the most recent UK Health Security Agency technical briefing (31 December 2021). Based on 528,176 confirmed or probable Omicron cases identified through PCR-based S-gene target failure (SGTF) in England and 573,012 Delta cases occurring between 22 November and 26 December 2021, the MRC Biostatistics Unit estimated that the risk of hospital admission with Omicron was 47% lower than with Delta and the risk of emergency care admission was 67% lower than with Delta. These analyses were adjusted for baseline factors including prior infection. The risk of hospitalisation after 3 doses of vaccine was found to be 81% lower compared to unvaccinated Omicron cases.

More broadly across South Africa, Wolter estimated that individuals infected with Omicron were 80% less likely to be admitted to hospital compared to Delta and the risk of severe disease was 70% lower compared to Delta. Based on 23,840 probable Omicron cases in Scotland, Sheikh estimated that the risk of reinfection was 10-times higher with Omicron (7.6% versus 0.7%) but that hospital admissions were reduced by 68%. Neil Ferguson analysed 306,194 COVID-19 cases across 1-14 December 2021 in England and estimated a 40-45% reduction in the risk of hospitalisation lasting one day or longer with Omicron compared to Delta (with a 0-30% reduction in intrinsic severity with Omicron) and that previous infection reduced the risk of hospitalisation lasting one day or longer by 61%.

Given that most infections are missed, with an estimated 40% of infections through the pandemic asymptomatic and potentially 70% of Omicron infections asymptomatic, the risk of severe disease with Omicron could be lower than these projections. Mirroring trends in South Africa, COVID-19 incidental admissions have risen to 33% during the Omicron wave in the UK (lhs) and average hospital stay times are falling towards 3-4 days (rhs):

Source: The Spectator

These observation studies support earlier hospital reports from South Africa. The Steve Biko/Tshwane District Hospital Complex in Pretoria published a detailed report on its early patient experience through 3 December based on 166 hospital admissions. The majority (66%) of hospital admissions were for diagnoses unrelated to COVID-19 and were uncovered by mandatory PCR testing before patients are admitted to hospital. The average hospital stay was 2.8 days versus 8.5 days for previous waves. 79% of patients were not requiring supplemental oxygen (in previous waves the majority of patients have required oxygen) and 80% of admissions were under the age of 50 years.

Similarly, the Netcare CEO commented that most patients at the group's Gauteng hospitals are showing milder symptoms compared to previous, such as a blocked or runny nose, scratchy or sore throat, and headaches. It was estimated that ~90% of COVID-19 patients did not need supplemental oxygen and are described as "incidental" patients. The majority (~75%) of the ~800 COVID-19 patients admitted to Netcare hospitals were unvaccinated and ~71% of patients were below 50 years of age, compared to only 40% in the first three COVID-19 waves. Whilst COVID-19 vaccination rates in South Africa remain low (32% first dose, 27% second dose), acquired immunity from previously completed Beta variant and Delta variant waves is estimated to be 75-80%. COVID-19 infection and mortality dynamics in South Africa and Europe:

Why is Omicron causing less severe disease but is more transmissible?

A series of animal and in vitro studies summarised below support the view that Omicron infections are more limited to the upper airways of the nose, throat and windpipe, similar to endemic common cold coronaviruses, and cause less damage to the lungs. Chai-Wai found that Omicron infects and multiplies 70-times faster in the upper airways than Delta, supporting a transmission advantage. However, Omicron multiplies 10-times slower in the lungs compared to the original D614G SARS-CoV-2 strain, which has been supported by Abnelnabi who found 3 log10 lower viral RNA load in the lungs with Omicron compared to the original D614G strain. Omicron in vitro and animal studies focused on lung cell infectivity:

Source: @EricTopol

The spike (S) protein of Delta is efficiently cleaved into two subunits, S1 and S2, which facilitates cell-cell fusion. Cleavage of the spike protein and viral fusogenicity are correlated with viral pathogenicity. The Omicron spike protein is only faintly cleaved, which means that it poorly infects and spreads in the lung and is less pathogenic compared to Delta and original D614G strain. Gupta have argued that efficient cleavage of the spike protein is also dependent on the presence of TMPRSS2, which is found in the lower airways of the lungs but not in the upper airways. Suboptimal Omicron spike protein cleavage reduces infection of the lungs where TMPRSS2 is found, but is less impacted in the upper airways which lack TMPRSS2 expression.

Population-level evidence suggests that Omicron has gained the ability to evade immunity generated from prior COVID-19 infections, something that Beta and Delta were unable to achieve. Up to 27 November, 98.7% of COVID-19 cases in South Africa were primary infections, with 1.2% second infections and 0.01% third infections, but with 14.2% of all reinfections occurring in November 2021. UK Health Security Agency risk assessment for Omicron:

Omicron's immune escape advantage together with the possibility it might be more transmissible than Delta and it might have a shorter incubation period than Delta (the balance of these three factors remains to be evaluated) means that Omicron has rapidly become the dominant variant in South Africa and also in the UK. The balance between the level of immune escape and intrinsic transmissibility is important when it comes to determining the ultimate level of spread, with the Barnard estimating a 12.8-fold increase in immune escape translates into 5-10% lower transmission relative to Delta and a 5.1-fold increase in immune escape translates into a 30-35% higher transmission rate. Kim et al have estimated that Omicron has a significantly shorter generation time of ~2 days compared to ~4 days for Delta. The UK Health Security Agency risk assessment for Omicron highlights the growth advantage over Delta and the immune evasion risks.

COVID-19 vaccine boosters initially provide 71-76% protection against symptomatic disease with Omicron, but this benefit begins to wane quickly. Four academic datasets and initial data from Pfizer/BioNTech provide a similar conclusion on vaccine efficacy against symptomatic infection with Omicron in a laboratory setting. An initial two dose COVID-19 vaccine series provides little protection based on a 25-40-fold reduction in neutralising antibody titres compared to the original Wuhan strain. However, two doses of the Pfizer/BioNTech COVID-19 vaccine followed by a booster resulted in a 2.6-fold reduction in neutralisation compared to the original strain with Omicron and ~a 15% reduction in neutralisation compared to the original strain with Delta. The Pfizer/BioNTech study found that the booster dose strongly increased the T cell response, with 80% of epitopes recognised by T cells not affected by Omicron mutations, suggesting that even the initial two dose COVID-19 vaccine series might protect against severe disease. Pfizer/BioNTech expect a variant-specific vaccine for Omicron to be available March 2022 as part of a 4bn dose total capacity for 2022. Research out of Hong Kong suggests that two doses and a booster of the Sinovac Biotech vaccine did not produce sufficient levels of neutralising antibodies to protect against Omicron. Pfizer/BioNTech in vitro neutralisation data versus Omicron:

Neutralising antibodies are only one part of the immune response following infection and vaccination, with T cells and memory B cells playing an important role especially when it comes to protecting against severe outcomes. Alessandro Sette’s group has shown that 98% of CD8 T cell and 95% of CD4 T cell epitopes are conserved across the various SARS-CoV-2 variants (including Alpha, Delta, Beta, Gamma) following an infection. With Omicron, the Sette group estimates that the proportion of epitopes that are conserved drops to 95% for CD8 T cells and 88% for CD4 T cells following an infection. When it comes to vaccination and focusing on spike protein mutations only, 86% of CD8 T cell and 72% of CD4 T cells epitopes are conserved with Omicron (in-line with the Pfizer/BioNTech data). We do not know what level of conservation is likely to preserve T cell responses, but these data suggest that T cell activity is far less impacted than neutralising antibody responses. T cell responses following vaccination:

Source: Sette group

The Sigal group’s in vitro study provided an important insight into the role of acquired immunity. Blood samples from six of the twelve individuals in the South African study (average age 57 years) came from people who were infected in the first original SARS-CoV-2 wave (on average 418 days before) and were then subsequently vaccinated (on average 27 days before the blood samples were taken). This is an important cohort given that it has been estimated that 75-80% of individuals in Gauteng province have been previously infected and >57% of people over the age of 50yrs in Gauteng province have been vaccinated. MorganStanley estimate that prior to Omicron, 55% of infections in Gauteng province have come in the Delta wave and 20% in the Beta wave, implying a higher level of natural immunity from (more recent) prior infection than in the six individuals studied by the Sigal group. 5/6 of these individuals had neutralising antibody titres in the 10,000-plus range to the original strain and ~1,000 to Omicron, implying a ~10-fold attenuation but relatively strong neutralisation against Omicron. Prior infection followed by Pfizer/BioNTech COVID-19 vaccine provided strong neutralisation against Omicron (green lines):

Gazit compared natural immunity to vaccine-induced immunity in a retrospective cohort study utilising medical records from the Israeli Maccabi Healthcare Services (MHS) centralised database over the study period of 1 March 2020 to 14 August 2021. The database analysis showed that vaccinated individuals not previously infected with SARS-CoV-2 had a 6.0-fold increased risk for breakthrough infection and a 7.1-fold increased risk of breakthrough symptomatic disease with the Delta variant compared to those previously infected between March 2020 to February 2021. The authors hypothesized that natural immunity, which is both mucosal and systemic, generated by the whole SARS-CoV-2 virus as opposed to anti-spike protein immune activation, offers broader protection than the immunity conferred by the Pfizer/BioNTech vaccine. COVID-19 infection rates per 100,000 at-risk days between 1 August and 30 September 2021:

Goldcompared protection from natural immunity, vaccine induced immunity and from hybrid immunity (infection plus vaccination) again using medical records from the Israeli MHS centralised database for the period of 1 August to 30 September 2021. The authors found that the risk of reinfection after recovery is about 7-fold lower than after double vaccination and that unlike vaccination, natural immunity remains relatively high even beyond 12 months. These data also suggest that vaccination after recovery offers limited significant additional benefit. New Danish data from the Statens Serum Institut support stronger protection from previous infection and hybrid immunity compared to vaccine induced immunity alone. Protection against COVID-19 infection from vaccination (green), from prior infection (orange) and from hybrid immunity (infection plus vaccination):

Source: Statens Serum Institut

The UK Health Security Agency published its technical briefing on 10 December 2021 containing an early assessment of COVID-19 vaccine effectiveness. The analysis included 56,439 Delta and 581 Omicron infections and suggested that COVID-19 vaccine efficacy against symptomatic disease with the primary course was significantly reduced with Omicron (~30-40% with Pfizer/BioNTech, limited with AstraZeneca/Oxford). However, from 2 weeks after a Pfizer dose, vaccine effectiveness increased to ~71% among those who received AstraZeneca/Oxford as the primary course and ~76% among those who received Pfizer as the primary course. COVID-19 vaccine efficacy against symptomatic disease versus Delta and Omicron (10 December 2021 report):

Source: Andrews et al

The UK Health Security Agency has published an updated technical briefing on 31 December with an assessment of COVID-19 vaccine efficacy against hospitalisations as well as an update on protection against symptomatic disease. The analysis included 169,888 Delta and 204,036 Omicron infections. Vaccine effectiveness (VE) against symptomatic disease continues to be lower for Omicron than for Delta and is waning significantly to ~40-50% by 10 weeks after a Pfizer/BioNTech (BNT162b2) booster dose (initial efficacy estimate with Moderna mRNA-1273 booster dose appears higher at 5-9 weeks). Vaccine effectiveness against symptomatic disease with Delta and Omicron:

Source: UKHSA

After 3 doses of vaccine, the risk of hospitalisation for a symptomatic Omicron case was estimated to be reduced by 68% (42-82%) when compared to similar individuals with Omicron who were not vaccinated. Combined with the protection against becoming a symptomatic case, this gives a vaccine effectiveness against hospitalisation of 88% (78-93%) for Omicron after 3 doses of vaccine. Although waning is seen in the effectiveness against symptomatic disease, there is insufficient data to assess the duration of protection against hospitalisation, which is expected to last longer. Vaccine effectiveness against hospitalisation from Omicron:

Source: UKHSA

In terms of the impact of immune evasion, 9.5% (11,103/116,683) cases were re-infections versus 0.4% (336/85,460) previously for Delta, which before adjusting for baseline factors implies >20-fold increase in the risk of re-infection with Omicron. With respect to household transmission, 13.6% of Omicron cases resulted in household outbreaks versus 10.1% of Delta cases, implying just a 1.4-fold increase for Omicron versus Delta which is lower than previous estimates (odds of non-household transmission estimated to be 2.6-fold higher for Omicron versus Delta). By comparison, the adjusted odds of household transmission was 2.6-fold higher for Delta versus Alpha.

Miyamoto have found that Omicron was highly resistant to neutralisation in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralisation against the Omicron were induced in vaccinated individuals who experienced breakthrough infections. The time interval between vaccination and infection was significantly correlated with the magnitude and potency of Omicron-neutralising antibodies. Reflecting this, Israel is now offering a 4th vaccine dose to individuals >60 years of age and to healthcare professionals as it faces a surge in Omicron infections.

Sigal studied previously vaccinated and unvaccinated individuals infected with Omicron close to when they had symptoms and ~2 weeks later. The group found a 14.4x increase in neutralising immunity against Omicron after 14 days, as well as a 4.4x increase in neutralising cross-immunity versus Delta. If Omicron is less pathogenic and can displace Delta, these data suggest that an infection with Omicron could generate hybrid immunity and protect against the emergence of future variants, which could have important implications for countries pursuing zero-COVID or more restrictive social policies.

The implications for the UK

In Gauteng province, it is estimated that 75-80% of individuals have been previously infected (most in the Delta wave) and ~57% of people aged >50yrs had been double-vaccinated. Across South Africa, 20% of individuals are immuno-compromised with HIV and 30% are living in poverty. Therefore the population in Gauteng province is not a typical population to extrapolate to the UK and more globally.
Comparing the first 30 days of the Omicron wave to the Delta wave, the percentage of cases which result in hospital admissions is 1.6% with Omicron compared to 4.5% with Delta, a ~65% reduction. Taking into account that ~70% of Omicron hospital admissions are "incidental" asymptomatic cases, they estimate that the chance of being hospitalised in the Omicron wave was up to 9-fold lower than during the Delta wave after 30 days. The proportion of ICU admissions not accounting for "incidental" cases was currently 12-fold lower in the Omicron wave compared to the Delta wave in Gauteng province after 30 days. COVID-19 vaccine uptake to 5 December (22.6m booster jabs as of 11 December):

Source: UK HSA

Turning to the UK, the percentage of cases which have resulted in hospital admission during the Delta wave has been 2.1% and after 33-39 days, 2.9% of Delta wave cases were admitted to hospital. At a comparable timepoint in the Omicron wave, the percentage of cases resulting in hospital admission is 1.2% (~60% lower). It is estimated that 33% of COVID-19 hospital admissions in England are incidental (i.e. in hospital for reasons other than the virus) which suggests a hospital admission rate for COVID-19 of ~0.8% compared to ~0.5% in Gauteng, South Africa.

Key adjustment factors to take into account include COVID-19 vaccine booster programs and the level of population acquired immunity. They estimate that up to 81% of the UK population has been infected using adjusted case fatality ratios, a similar level to that estimated in Gauteng province. In contrast, the vaccination program in the UK is significantly more advanced. Focusing on the age groups most at risk of hospitalisation, >84% of those aged 60 years or over have now had a booster jab, where protection against symptomatic infections is estimated to be ~40-70% and protection against hospitalisation is estimated to be ~88%. They estimate combined immunity against symptomatic disease (booster vaccine and hybrid immunity) in the UK is currently >65% at this point in the Omicron wave. Estimating combined immunity in the UK (vaccine plus acquired immunity against symptomatic COVID-19 (booster jabs have risen to 24.64m); over 70% of hospitalisations have historically been in the >50yrs demographic:

MorganStanley here have assumed that the Omicron wave started in the UK on 21 November and that infections are doubling every two days. Before taking into account booster vaccine and hybrid immunity, we have assumed that daily infections peak after 40 days on 2 January 2022 (compared to ~23 days in Gauteng province), with 2.5m daily infections, the majority of which are expected to be asymptomatic or mild. This could clearly prove highly conservative, with an implied ~60% of the UK population being infected with Omicron compared to ~30% in Gauteng province based on extrapolation. Comparing unadjusted hospital burden of the Omicron wave to previous waves:

Source: Morgan Stanley Research

Applying a hospital admission rate of 0.6% would result in a total of close to 270,000 hospital admissions (Omicron plus Delta wave) through to 1 March 2022. On the basis the average hospital stay time for an Omicron infection is 3 days (2.8 days in Gauteng province), they would estimate that on 7 January 2022, at peak, there would be ~47,000 individuals in hospital with COVID-19 before adjusting for vaccine-based immunity. So whilst the total number of admissions would be projected to be -16% below the Alpha variant / Winter wave of 2020-21, the number of hospital cases would be projected to be 19% higher at peak. Comparing the Omicron plus Delta wave 2021-22 (unadjusted for vaccine immunity) to previous infection waves:

Applying a collective immunity of 70% in preventing severe disease leading to hospitalisation against our un-adjusted base case scenario and assuming ~one third of patients in hospital are "incidental COVID-19 patients" would result in ~120,000 COVID-19 hospital admissions over the Omicron plus Delta wave period and peak hospital cases of ~21,000 (compared to 39,254 at the January 2021 peak). Compared to recent winter flu season in the UK, there were an estimated 46,215 hospitalisations in the winter of 2017/18 (~26,000 deaths) and an estimated 39,670 hospitalisations in the winter of 2018/19. Vaccine efficacy assumptions versus Omicron (Barnard et al, LSHTM):

Source: Barnard et al

Barnard et al from the London School of Hygiene and Tropical Medicine have released a preprint modelling study for the Omicron wave in England. The group constructed scenarios based on low and high estimates of immune escape, as well as low and high estimates of transmissibility of Omicron based on S-gene target failure (SGTF) PCR data from England. By using low and high estimates of booster effectiveness, the group modelled four main scenarios: (1) low escape + high booster efficacy; (2) low escape + low booster efficacy; (3) high escape + high booster efficacy; (4) high escape + low booster efficacy, in order from most optimistic to most pessimistic. Importantly, the group assumed the same level of disease severity for Omicron versus Delta, despite evidence to date to the contrary. Under the most optimistic scenario (low immune escape, high booster efficacy), the group estimates that there will be 20.9m Omicron infections and 175,000 hospital admissions. Under the most pessimistic scenario (high immune escape, low booster efficacy), the group estimates that there will be 34.2m Omicron infections and 492,000 hospital admissions. Omicron epidemic scenario analysis (Barnard et al, LSHTM):

Source: Barnard et al

What is the current situation in the UK?

With the holiday period introducing volatility into the COVID-19 tracking data, the focus is on whether UK Omicron cases in leading-indicator London will continue to decline from the recent 23 December 2021 peak or begin to rise again, with COVID-19 hospital admissions lagging by about a week. Therefore London is currently our primary focus as a proxy for other regions of the UK (it appears to be 10-14 days ahead) and other Northern Hemisphere countries going through winter respiratory infection seasons. At this stage, London appears to be following a similar trajectory as Gauteng, South Africa, but the picture will become clearer over the next two weeks. London COVID-19 cases by specimen date (upper), patients admitted to hospital (lower):

Source: https://coronavirus.data.gov.uk/

These data are supported by ZOE COVID study which suggests that the R value for London is currently between 0.8-1.0 which daily cases falling since just before Christmas Day. The UK government has indicated that further COVID restrictions are unlikely to be introduced based on the current data, with the potential that hospital admissions in London may have peaked. It will be important to see what impact New Year celebrations, inter-generational mixing and the return to school will have on infection rates in London over the next 2 weeks. ZOE COVID Study estimated daily COVID-19 cases in London:

Source: ZOE COVID Study

Compared to the January 2021 Alpha/winter wave peak, Omicron wave cases in London appear to have declined to 50% above the Jan-21 peak whilst hospital admissions appear to be plateauing at ~50% below the Jan-21 peak and mechanical ventilator cases are ~80% below the Jan-21 peak. London Omicron wave compared to the Alpha/winter wave peak:

Given reporting delays over the Christmas holiday period, the following exhibits highlight the broader picture across England. Growth in cases by specimen date, some 2-5 days following infection, is continuing to moderate but unlike London appears to be growing >20% week over week. Hospital admissions have increased by over 70% for the week ending 31 December, but appear to be moderating somewhat in the last few reporting days. England COVID-19 cases by specimen date (upper), patients admitted to hospital (lower):

Source: https://coronavirus.data.gov.uk/

Compared to the January 2021 Alpha/winter wave peak, Omicron wave cases in England appear to have risen to 135% above the Jan-21 peak whilst hospital admissions have risen to ~50% below the Jan-21 peak and mechanical ventilator cases remain ~80% below the Jan-21 peak. England Omicron wave compared to the Alpha/winter wave peak:

COVID-19 case growth rates across England:

Healthcare systems are under pressure in the UK as hospitals aim to maintain urgent and high priority elective care activity. The situation is distinctly different from January 2021, reflecting ~60% fewer patients in critical care for COVID-19 respiratory problems, with the key challenges being a combination of staff absences, which could become as high as 25%, and having to isolate Omicron patients, whether incidental or not, to avoid cross infection. In London, the number of COVID-19 hospitalised patients is at 36% of the 18 January 2021 peak (for England, 29% of the Jan-21 peak). London COVID-19 patient hospital cases (of which just 6% require mechanical ventilation):

Hospital trust chiefs are reporting a high number "incidental COVID" asymptomatic patients (estimated to account for 33% of patients) and are not seeing large numbers of severe covid type respiratory problems needing critical care (just 6% of hospitalised patients). However, there is arguably more pressure on the NHS compared to January 2021 with more planned urgent and emergency care cases that cannot be delayed and the booster campaign remaining resource intensive. If cases were to continue to rise, hospital trusts would likely have to set up extra surge capacity which would in turn put pressure on less urgent elective procedures. Whilst there has been some progress in terms of speeding up hospital discharges to reduce the demand on G&A beds, growing numbers of COVID patients and rapidly increasing staff absences are increasing pressure on NHS services like step down and social care. Challenges are being reported for ambulance trusts given the need to ensure that every ambulance has trained paramedics, which is one of the reasons why a number of trusts have declared internal critical incidents over the last few days. Hospital admissions and NHS COVID related absences in London:

Source: The Spectator

What does this mean for other regions?

For countries which have either transitioned through a Delta wave, such as India or Indonesia, or where acquired immunity from prior variants such as Gamma meant that they did not experience a Delta wave, such as Brazil and Argentina, Omicron's immune escape advantage and rapid spread suggests these countries will likely experience another infection wave. Like South Africa, these regions have a relatively young population, but their COVID-19 vaccine programs are more advanced, especially across South America, suggesting that Omicron might potentially lead to a milder spectrum of disease in these regions (Exhibit 32). For South Africa, antibody surveys suggested ~50% prior levels of infection in January 2021 and this is estimated to have reached ~75-80% ahead of Omicron. Acquired immunity is both mucosal and systemic, against all 29 proteins in the SARS-CoV-2 virus, with Israeli cohort studies suggesting it is more durable than vaccine-based immunity. Comparing COVID-19 pandemic parameters in South Africa with other regions:

Many parts of Europe and the US are still transitioning through Delta waves towards acquired immunity thresholds under the protection of COVID-19 vaccines, with wastewater studies uncovering significant regional variations in the US where clinical cases are running significantly below SARS-CoV-2 virus levels in the South and West, indicative of high levels of asymptomatic infection. European countries such as Germany, Austria, the Netherlands and Norway have experienced low levels of prior infection and therefore are likely to experience the most significant residual morbidity and mortality burden from this point.

The populations in these countries are older and there will be greater reliance on the booster programs to extend protection against severe disease in vulnerable groups ahead of the anticipated spread of Omicron. The early assessment of COVID-19 vaccine effectiveness published by the UK Health Security Agency published in technical briefings on 10th and 31st December will lead to direct comparisons between countries based on how advanced their booster rollouts are (Chile 57%, UK 43% of the total population, Germany 39%, France 37%, Italy 33%, Spain 29%, US 21%). There are ~595k episodes of influenza in West Europe each year with a direct mortality rate (excluding pneumonia) of ~1.5% and as such we await more data to understand the relative burden Omicron might carry within the context of a normal respiratory virus winter season. There is a possibility that hospital systems under pressure in countries such as Germany as identified by Chapman will reach with an abundance of caution and introduce lockdowns over the coming weeks. We continue to believe that "herd immunity" driven by infections against a backdrop of protection from COVID-19 vaccines and therapeutics is the key to exiting the pandemic and that "zero COVID" policies will not prove to be sustainable against the Delta and Omicron variants with the potential for a perpetual cycle of lockdowns.

Graphs:

Hospitalisation in Gauteng:

Cases and hospitalisation of South Africa in Beta, Delta, and Omicron waves:

Time series of primary series/booster vaccinations (top), new COVID cases (middle) and current hospitalisations due to COVID (bottom) in the US

Source: Morgan Stanley Research, Our World in Data, Department of Health and Human Services, JHU CSSE.

Emerging hot spots in the US. The x-axis is growth rate of new cases compared to last week, the y-axis is the new case per hundred, and z is the latitude. Each state is color coded by vaccination rate.

 


 


Justin Stebbing
Managing Director
 

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