Many of the questions below have received updates, but a few highlights include:
Views on Omicron are becoming more polarized with some claiming it is nothing to worry about while many businesses, schools, and healthcare providers are gravely concerned about how Omicron will impact their settings. Many are accepting that COVID-19 will be with us beyond Omicron, while others are continuing to experience “pandemic fatigue” and are immobilized to act, in part because of limited resources.
The United States and the world are in a much better position today than we were in January 2020; we are better prepared to respond to Omicron than we were to the original COVID-19 strain in January 2020. The mRNA platform can adjust vaccines for new variants if needed, genomic sequencing has increased globally with improved information-sharing between partners, many governments and decision-makers now understand the importance of early action, rapid tests are becoming more widely available and accessible, there are two very promising antiviral pills to treat COVID-19, and we have vastly greater knowledge of the SARS-CoV-2 virus.
Yes, everyone has “pandemic fatigue” and many have “plague amnesia”; we want to move on with our lives and get back to normal. But now is not the time to let up on important prevention and mitigation measures because COVID-19 is with us for the foreseeable future. All of us - corporate leaders, governments, researchers, and community members - have an important role to play in adjusting to this “new normal”.
The CDC updated and shortened the recommended isolation and quarantine period for the general population from 10 days to 5 days following a positive test result, provided that the individual is asymptomatic or symptoms are resolving. Below, we describe PHC’s perspective on this update.
A UK Health Security Agency study supports a 7 day self-isolation with 2 negative antigen tests 24 hours apart. By 7 days, 1 in 6 (16%) were still infectious compared to 5 days where 1 in 3 (33%) were still infectious.
Despite efforts by health institutions to increase Omicron testing and sequencing, test availability is becoming scarce (especially for at-home rapid tests) and delays for lab test results are increasing. Due to this shortage the White House and USPS are finalizing a plan to start shipping test kits to U.S. households.
PHC believes CDC's recent guidance was not based on public health science for Omicron but on the need to maintain workforces in the short-term. This shortened isolation period may backfire, though, with more infections based on early Omicron data suggesting the average infectious period is beyond 5 days. PHC strongly urges organizations to require a negative rapid test in order to exit isolation at the end of 5 days.
Omicron is widespread in the U.S. There are immediate steps we can take to protect lives and livelihoods. We know the layers of defense, or “Swiss cheese” model, that work to slow the spread of COVID-19:
The Omicron variant probably did not evolve from the Delta variant, rather it likely pre-dates the Delta variant. We can tell this because the mutations in Omicron’s genome can serve as a molecular clock, allowing an estimation of when it evolved from an existing strain of SARS-CoV-2. That molecular clock suggests it evolved around June of 2020. The scientific community is moving rapidly to analyze Omicron genomes and there will be a better understanding of its family tree in the coming month. There are a number of possible scenarios for how it evolved, including:
As global sequencing to detect Omicron increases, missing links in the recent Omicron family tree may be detected, including from older frozen specimens. This may help fill in the gaps in our knowledge of where and when it emerged.
We will likely never identify the exact origin case.
Most countries and territories have confirmed Omicron cases (source 1, source 2). As we predicted, Omicron cases are exploding globally and in the U.S. Cases in the U.S. have risen faster, in part due to robust testing and sequencing efforts to detect the new variant. Currently, the U.S. has the highest number of daily new cases relative to all other countries. This is more than twice as many cases as the UK, which has the second most daily new cases.
Wastewater surveillance (testing of wastewater from toilets, showers, sinks, etc. for molecular / RNA analysis) has identified unprecedented levels of Omicon. The identification of cases through wastewater surveillance, followed by positive Omicron cases demonstrates the ability for wastewater to be an early indicator of disease spread and detection. This U.S. map shows to date where SARs-CoV-2 has been identified in wastewater across the United States. Boston and California show signs of decreased levels of virus in wastewater – a sign that the virus may begin to trend downwards in those particular areas.
Omicron cases will continue to rise globally, due to both rapid spread and to improvement in Omicron detection in countries (like the United States) that were previously not doing enough genomic sequencing. For countries with less robust sequencing capabilities, as the saying goes, “absence of evidence is not evidence of absence."
Omicron is currently the dominant variant in the U.S.,currently accounting for ~95% of new cases in the U.S. In January, the daily count of new COVID-19 cases (including both Delta and Omicron) reached >1 million – the highest case count the U.S. has experienced. Currently, the U.S. has the highest number of daily new cases relative to all other countries. Cases in the U.S. have risen faster, in part due to robust testing and sequencing efforts to detect the new variant.Hospitalizations are also surging in many areas of the U.S., and many states are implementing crisis standards of care.
NewsNodes Omicron Tracker
As U.S. sequencing continues to increase, we will continue to see evidence of the dominance of this variant within the United States.The precipitous growth of cases in the U.S. is due to both rapid spread and to sequencing efforts “catching up” with the cases that have already been circulating and eluding prior detection.
Omicron contains ~50 notable mutations; some of them have been previously seen in other COVID-19 variants whereas some are new. There are ~30 notable mutations in the spike protein alone that may allow Omicron to get into cells quickly and avoid neutralization by antibodies that develop after natural illness and vaccination. This is one potential explanation for how Omicron is able to infect vaccinated and previously infected people at higher rates than Delta or other variants.
Unknown. Wildcard. As we saw with Delta, some initially worrisome mutations ended up having little impact. Both in vitro laboratory studies and observational data will substantially inform if and how Omicron’s mutations are expressed. As new Omicron data is known and studies are conducted, we will share that here and make predictions where we think we can.
Early information suggests the mode of transmission for Omicron is the same as prior variants, meaning it is mainly spread through air and droplets (breathing, singing, talking, coughing, sneezing.)
Omicron will have identical modes of transmission as previous COVID-19 variants. This is another reason why we are not in the same situation as February 2020, because we now know how COVID-19 is spread and know how to implement layers of protection to stop / slow the spread.
Exponential community spread of Omicron is rising across Europe and the United States. While it is too early to draw definitive conclusions about how easily Omicron is spread (i.e. the transmissibility “R0”), many “superspreader events” and mounting data from HKUMed strongly suggests Omicron is more transmissible than the Delta variant. The underlying attributes of Omicron that enable it to spread quickly (higher R0, significant immune escape of antibodies formed by the vaccine or previous infection, or both) are still being determined. One early study suggests a majority of Omicron’s spread is due to its ability to circumvent vaccine protection rather than an inherent increase in basic transmissibility. Additional studies will help to confirm or refute this hypothesis.
Omicron also appears to replicate, or grow to reach infectious viral loads, faster in cells than Delta. The UK is reporting the doubling time of Omicron cases to be ~2.5 days for sequenced specimens and less than 2 days for Omicron detected via PCR tests with S Gene Target Failure (SGTF). Additionally, the UK is experiencing increased household transmission and secondary attack rates (the percentage of people in a specific setting, such as a household, who develop COVID-19 infection from their infected household member). Data from the UK also shows that the secondary attack rate of Omicron is 21.6% of exposed household members versus 10.7% of those exposed to the Delta variant (Table 3).This data also supports why South Africa experienced such a large influx of cases and how Omicron ultimately surpassed Delta. However, clinical data and individual immune response are needed to confirm these findings and understand more about the severity of Omicron infection.
A study out of Denmark shows a reduction in transmissibility of Omicron among people who had a booster shot
PHC predicts that Omicron will prove to have transmissibility (R0) comparable to or higher than that of the Delta variant.
A question we are asking is, “How long did it take for countries to report confirmed cases of different variants?” This is an imperfect and rough proxy for speed of international spread, but a useful comparison especially for Delta and Omicron. Despite substantially reduced air travel, relative to before the pandemic, the speed at which Omicron has been reported by countries is substantially faster than any previous variant.
A global surge in Omicron cases has already led to significant staffing shortages and disruption to public and private institutions. Businesses should implement prevention and mitigation measures to limit the disruption to global supply chains, business continuity, and healthcare access.
The analysis below shows the rate at which each variant was publicly reported as a confirmed case by a country. It is important to recognize that many factors are at play here, including the amount of testing and sequencing a country is doing (how fast will they detect it?), political will to publicly share confirmed cases as soon as they are detected, etc.
*Note: For Delta, the curve above shows the number of days since it was detected in the 3rd country. We excluded two early outlier countries where Delta was detected in samples far before it started to spread widely.
The Delta variant of SARS-CoV-2 has an R0 (a measure of transmissibility*) ranging between 5 and 8. Omicron may have an unmitigated R0 similar to Delta, making it highly transmissible.
Incubation period is the time from virus/pathogen exposure (“infection”) to the start of symptoms. Infectious period is the time when a person can spread the virus to another person. Data from recent outbreaks of Omicron demonstrate that the incubation period of Omicron may be as short as 3-5 days (compared to 5-7 days for Delta and 7-14 days for the original strain).
A Norwegian study from an Omicron outbreak suggests that the time between virus exposure and symptom onset/positive test was 3-4 days, with a range up to 8 days.
Generation time (also known as generation interval) is the time from infection-to-infection, or the time between infection of a primary case and its subsequent infection of a secondary case. This is a really important number in determining the rate of spread. Very preliminary estimates of generation time are between 3-5 days, meaning Omicron is spreading very quickly.
The incubation period will likely be ~3-5 days and the infectious period will likely be ~6-14 days. Note, this does not include immunocompromised persons who become chronically infected.
Virulence is the severity or degree of harm of a disease. We are learning more about Omicron’s virulence as case numbers rise.
A study from the CDC, the White House, and Kaiser reports that when compared with Delta, people testing positive for the Omicron variant have a 53% lower risk of symptomatic hospitalization, 74% lower risk of ICU admission, a 91% lower risk of death, and a 70% decrease in hospital length of stay if hospitalized.
Of note, patients diagnosed with the Omicron variant in this study were more likely to be between the ages of 20-39 years and less likely to be older adults and young children than patients diagnosed with the Delta variant in the same population. While the decrease in severity of Omicron held true across all demographics in the study when compared to Delta, it is important to remember we do not yet have enough data to say if Omicron will be less severe for the most at-risk populations (i.e. immunocompromised, older adults, young children).
The ZOE COVID study in the UK reports the top five symptoms associated with Omicron infection are runny nose, headache, fatigue, sneezing, and sore throat. This information was obtained from review of cases in the London area, where the case rate is higher than any other region in the UK. At this time, there is no apparent difference between the symptom profile of Omicron and that of Delta.
Back in February/March 2020, we were watching closely how COVID-19 spread through the Diamond Princess cruise ship because we knew it was an early indicator (the canary in the coal mine, if you will) of what would happen when the virus reached skilled nursing facilities, prisons, and other high risk congregate settings. While many were claiming COVID-19 was no different than the flu, our focus was on that ship. Although imperfect, early conclusions could be drawn about the attack rate, generation time, and virulence just from the Diamond Princess alone, and those predictions proved to be true. As Omicron spreads through the U.S., high-risk congregate settings (i.e., skilled nursing facilities, prisons) provide the clearest picture of the severity of illness that Omicron can cause.
Multiple studies (e.g., study 1, study 2) indicate Omicron is less likely to induce COVID pneumonia than other strains, but other measures of severity are still lacking data. In vitro lab studies (study 1, study 2) as well as mouse models (study 1, study 2, study 3, study 4) report that there is decreased lung cell infectivity – suggesting Omicron doesn’t attack lung tissue as strongly as past variants.
Omicron will probably have equal or lower severity (virulence) compared to Delta across all demographic groups. However, given our prediction that prior infection with COVID-19 (natural immunity) will likely offer poor protection against Omicron, we suspect that the hospitalization rate (a percentage of positive cases that are hospitalized) and case fatality rate (a percentage of positive cases that result in death) in the unvaccinated could be similar to Delta. It is indisputably clear that the overall number of hospitalizations are climbing rapidly and PHC predicts the impacts of this will grow, causing systemic impacts to essential workforces and services, especially the U.S. health system.
We cannot afford to have a bad flu season, or even a “normal” flu season, on top of COVID-19, given both Omicron and Delta have the potential to severely stress healthcare systems, cause hospital bed and medical supply shortages, and drain already exhausted healthcare workers. Everyone needs to get their influenza vaccine, as soon as possible, to protect themselves, their loved ones, our healthcare system, and our economy.
Omicron underscores the fact that global HIV treatment and control, particularly in under-resourced countries, is a matter of global health security. Untreated HIV leads to an immunocompromised host, enabling COVID-19 to continue replicating and mutating within that host for up to six months. The inability of the host’s immune system to clear the virus creates an internal microcosm of molecular evolution. This is analogous to how many multi-drug resistant tuberculosis (TB) cases arise.
The U.S. FDA has issued a statement about the impact of SARS-CoV-2 mutations on the performance of COVID-19 molecular tests: The FDA acknowledges that mutations in the viral genome can result in changes to viral proteins and therefore have an effect on the performance of molecular tests. Specific EUA-authorized tests whose performance might be impacted by mutations associated with the Omicron variant have been identified and the recommendation from the FDA is to avoid using these specific tests until the ability of the tests to detect Omicron can be validated.
In the interim, the FDA has identified molecular tests that have been successful in identifying patterns that may be associated with the Omicron variant, specifically, a phenomenon called S gene target failure (SGTF), which produces a noticeably different signal in test results (essentially a clue that is left behind after a portion of the analysis fails). By running these specific molecular tests (e.g., “TaqPath” PCR from Thermo Fisher), a laboratory can indicate a suspected Omicron case.
UK studies continue to show that tracking SGTF is a predictive indicator of Omicron cases, even before genomic sequencing has been completed to provide definitive confirmation. This is also how many Omicron suspects are being identified in many countries. The U.S. has not yet organized a collaboration of laboratories to track Omicron suspects using this approach. The U.K has been tracking variants in this way since December 2020, and it is proving incredibly useful to track Omicron growth in near real-time.
Testing for S-gene dropout as an early indicator of Omicron cases will likely become very useful in tracking Omicron’s geographic distribution and growth globally. Indeed, the UK is already using this approach as a means of surveillance and reported in a technical briefing on Dec 3, 2021 that the numbers of S-gene target failure (SGTF) are increasing. Additionally, a targeted PCR for Omicron will probably be developed and used by some laboratories in the near future.
The UK Government announced that there is no impact on rapid test sensitivity to Omicron, based on laboratory data, however, there is emerging evidence from a real-world study indicating that several rapid tests that use nasal swabs may fail to detect some Omicron cases in the first days of infection. One preliminary explanation is that in the beginning of an Omicron infection, the virus may be more prominent in the throat as opposed to the nose.
This study comparing the test results of PCR and a particular rapid antigen test dispels any concerns that antigen tests will not work against Omicron.
Some rapid tests target the nucleocapsid protein, not the spike protein, and thus are likely to remain effective against Omicron. Currently, no rapid COVID-19 test manufacturers (either antigen or molecular) have confirmed a decline in efficacy for the Omicron variant. The UK has also been using an alternative type of test (lateral flow rapid antigen tests) and found similar sensitivity to detect Omicron compared to Delta.
There is a low probability that the currently available rapid antigen tests will lose efficacy based on a mutation preventing them from detecting the viral antigens. However, if the location where the virus primarily grows in the body shifts away from the nasal area, then there may not be enough virus collected on a nasal swab alone for the test to detect. While not yet officially recommended by rapid test manufacturers, swabbing the back of one's throat and nose may improve the test's ability to detect Omicron infections.
PHC predicts there is moderate risk that rapid molecular tests may have reduced efficacy based on the mutations found in the Omicron variant (i.e. some rapid molecular tests may not appropriately detect COVID-19 infections in a person that contracts the Omicron variant).
It is clear that vaccine effectiveness against disease caused by Omicron is lower than effectiveness against the Delta variant.
Numerous studies (study 1, study 2, study 3, study 4, study 5, study 6) have compared how effective various combinations of natural and/or vaccine-induced immunity were against variants of SARS-CoV-2, including Omicron. People who had received two vaccine doses had low to no ability to neutralize Omicron (meaning there was almost no protective effect from two vaccine doses against Omicron). Omicron’s reinfection rate was five times higher than Delta’s, which suggests low levels of residual immunity from prior infection with other variants.
However, a report from the UK Health Security Agency shows that getting the booster vaccine produced a moderate amount of neutralization (i.e. protection) against Omicron, and confirmed that a booster dose is more effective against the Omicron variant than 2 doses alone. Additionally, a study from a large health system in South Africa reports that the vaccine’s (Pfizer, 2-doses) ability to prevent hospitalization was reduced from 93% against delta to 70% against Omicron, further exemplifying the need for a booster.
This graph shows that while vaccine effectiveness is generally lower with Omicron, new cases are increasing more sharply among unvaccinated individuals, meaning it is ever important to get fully vaccinated.
The UK is reporting that Omicron is capable of immune evasion (including natural and vaccine derived immunity) based on multiple laboratory studies and real world vaccine effectiveness data for asymptomatic and mild cases. One study shows there is substantial immune escape from Omicron in dual vaccinated individuals and partial immunity following a booster dose of mRNA vaccine.
This table is from a U.K. technical briefing that describes vaccine effectiveness against hospitalization for Omicron. This shows a significant increase in protection from Omicron hospitalization after a 3rd dose (booster).
Scientists at the Walter Reed Army Institute have announced a vaccine that protects against all variants of SARS-CoV-2, including those in the past. It has passed phase 1 trials, but must still pass phase 2 and 3 trials.
We believe Omicron is going to have a meaningful reduction in vaccine efficacy, however the magnitude is yet to be determined. These early antibody neutralization studies are concerning, but it is not straightforward to translate a reduction in antibody neutralization into a reduction in overall vaccine efficacy; there are many other factors in play. Lab tests are one data point, and how the variant behaves out in the wild and up against the full landscape of our complex human immune system is another.
Note that the world is now a mixed bag of different immunity profiles because of different vaccines and different variants.
We correctly predicted that being fully vaccinated (which PHC defines as inclusive of a booster dose), combined with natural immunity from a past infection, affords the best protection against the Omicron variant. This prediction was based on the very high efficacy of booster shots, which help generate a robust immune response even beyond what the initial vaccine generated. Booster shots not only trigger strong B-cell response (the cells that make antibodies), but also trigger strong T-cell response, creating immune protection against many different flavors of COVID-19 variants regardless of specific spike protein mutations. As a precaution, vaccine manufacturers are already pursuing mRNA vaccines that will target the new changes to the spike protein in Omicron. However, vaccine development will take months.
The most pressing global priority is to vaccinate the entire world against COVID-19, prioritizing vulnerable populations and under-resourced nations. It is not enough to make vaccines “available;” efforts to operationalize culturally appropriate vaccine messaging and distribution must accompany that availability.
Governments should highly encourage and push for people to get their booster shots given the effectiveness of boosters in comparison to two doses of vaccine.
The United States is lagging behind many other countries in the percentage of people who have received booster vaccines. It is critical that the U.S. increases public messaging surrounding the positive impact that boosters play in the resistance against Omicron and future variants.
On December 21, Israel approved a fourth dose of a COVID-19 vaccine for persons over 60 years and healthcare providers.
Numerous governing bodies will begin to reclassify “fully vaccinated” as including a booster vaccine. Additionally, we anticipate heightened efforts from the G20 to further global vaccination campaigns.
Taking a long-term view, it is not realistic to think that the entire world can be vaccinated/ boosted against a new variant every 9-12 months. Indeed, we have not even achieved global vaccination yet with our current vaccines. We predict that in the next 1-2 years there will be promising developments toward a vaccine that covers all variants and whose protection lasts longer than 6 months.
Vaccine manufacturers and research laboratories are currently assessing vaccine efficacy against Omicron. Thanks to critical work on rapid mRNA vaccine development earlier in the pandemic, and how the mRNA platform was constructed, vaccine manufacturers report they will be able to adjust the vaccines for new mutations, if necessary, in a matter of months. On January 4,2022, the CDC updated their recommendation for when many people can receive a booster shot, shortening the interval from 6 months to 5 months for people who previously received the Pfizer-BioNTech COVID-19 vaccine.
On Dec. 8, 2021 Pfizer announced in a press release findings from their preliminary testing: 3 doses of the Pfizer COVID-19 vaccine neutralizes the Omicron variant, while 2 doses show “significantly reduced neutralization titers”. This means that only 2 doses likely provides less protection against Omicron.
Pfizer also “continues to develop a variant-specific vaccine against Omicron in case it is needed with the aim to induce high levels of protection against disease as well as a prolonged protection” with first batches anticipated by March 2022.
On December 20, Moderna announced that the authorized booster dose and a higher dose demonstrated a 37-fold and 83-fold increase in the antibodies that neutralize the SARS-CoV-2 virus. This is incredible validation of the benefit and importance of a booster dose, and specifically of the Moderna vaccine.
Laboratory assays show nearly all of the monoclonal antibody treatments used to prevent severe disease have reduced efficacy against the Omicron variant. However, other treatments have been introduced to treat Covid-19, like Paxlovid, an antiviral pill. It has been FDA approved in the US to treat COVID-19 and reduces hospitalization and fatality rates.
A recent study indicates that Omicron remains largely sensitive to eight of the most important anti-SARS-CoV-2 treatments, including remdesivir and molnupiravir (antiviral medications).
Current mRNA vaccines coupled with booster shots will continue to provide the best protection against Omicron while Omicron-specific vaccines are being developed.
In the near future, patients with COVID-19 may need to have their virus sequenced (viral genotyping) to determine if a monoclonal antibody will be effective or not, based on which variant they have. Different treatments for different variants is a very real possibility.
Mask requirements on airplanes, trains, buses, and other modes of transportation will be enforced through March 18th. Additionally, new testing and quarantine requirements (i.e. requirement for proof of negative COVID-19 test for all air passengers boarding a flight from a foreign country to the U.S.) have been put in place for international travelers including both vaccinated and unvaccinated persons.
Additionally, some jurisdictions like Los Angeles County are offering free rapid COVID-19 tests to international travelers arriving at the LAX international terminal.
There will probably be more travel restrictions, testing requirements, and mandatory quarantine after travel.