Variants:

Is there evidence that the BA 4/5 strains are more virulent and more infectious?

"Both BA.4 and BA.5 are more infectious (according to this preprint). There is no good evidence at this time to support them being more severe (https://www.ecdc.europa.eu/en/news-events/implications-emergence-spread-sars-cov-2-variants-concern-ba4-and-ba5). Initial studies from South Africa do not suggest increased virulence while in other populations e.g. Portugal there was an increased hospitalization observed. The severity of BA.4/5 is likely to be influenced by specific population profile, vaccination status, and prior infections. Importantly, vaccination in addition to other non-pharmaceutical interventions (wearing a mask) are still effective at minimising the risk of infection from these variants."

What do we know about the emerging Centaurus variant that has recently arrived in the UK?

"BA.2.75 is a relatively newly emerged variant that has some genetic features that make it worth watching, has been found in multiple countries, and has shown a growth advantage in India. Importantly, India doesn’t have much BA.5 so how BA.2.75 will compete against that is not yet well-understood. WHO has flagged it as a subvariant under monitoring because it 1) belongs to a currently circulating variant of concern (i.e., omicron); 2) shows signals of a transmission advantage; 3) has genetic changes known or suspected to confer a fitness advantage relative to other circulating variants (https://www.who.int/activities/tracking-SARS-CoV-2-variants). It is being monitored closely but it is too early to make any further conclusions about, for example, severity.

A recent study suggests that it is less immune evasive than BA.4/5 with previous omicron infection and vaccination. At the same time the study found that it is more immune evasive in individuals with prior Delta infection. Hence the growth advantage of BA.2.75 might very well be population dependent. Indeed this is similar to BA.4/5 which did not lead to huge waves in South Africa (https://twitter.com/yunlong_cao). Importantly, vaccination in addition to other non-pharmaceutical interventions are still effective at minimising the risk of infection from this variant."

Further technical details:

https://twitter.com/PeacockFlu/status/1542501382678147072

https://twitter.com/jbloom_lab/status/1542526095299203074?lang=en

Are the new variants managing to evade the immune system? What does this mean?

"Because of the genetic changes in BA.2.12.1, BA.4, and BA.5 (and likely BA.2.75), the immunity built up to earlier versions of SARS-CoV-2, like Delta and BA.1 Omicron, is not as effective at neutralising these newer variants, especially BA.4 and BA.5. That means that more virus particles of these variants will be able to get past existing antibodies to get into our cells to cause an infection. This is especially true if antibody levels are waning if it’s been a while since the last vaccination/infection. However, there are other types of immunity beyond just antibodies that will likely still protect against severe infection with these variants. Importantly, vaccination in addition to other non-pharmaceutical interventions are still effective at minimising the risk of infection from these variants."

https://pubmed.ncbi.nlm.nih.gov/35790190/

https://pubmed.ncbi.nlm.nih.gov/35775166/

https://pubmed.ncbi.nlm.nih.gov/35772405/

https://pubmed.ncbi.nlm.nih.gov/35731894/

Reinfection:

Are people becoming reinfected more quickly and if so, why?

"I don’t know that we have evidence that people are being reinfected more quickly. However, with more people having had COVID, the chance that a new infection being is in someone who has already had the disease is higher.

Back in August when almost no-one in the ACT had had COVID, the chance of an infection being in someone who had already been infected was really low. Now, not so much. Immunity from vaccines and previous immunity works incredibly well to prevent severe disease. It is pretty good at preventing reinfections with the same vaccine/first infection variant (depending on the time since the last vaccine/infection). But as new variants emerge, they are better at evading pre-existing immunity, especially if it’s been a while since the last vaccination/infection. Indeed BA.2.12.1 and BA.4/5 have been shown to have better immune escape from prior Omicron (BA.1/BA.2) infections. Importantly, vaccination in addition to other non-pharmaceutical interventions are still effective at minimising the risk of reinfection."

After COVID-19, how soon should people consider themselves at risk of getting it again and how severe are reinfections likely to be?

"Reinfections tend to be much less severe on average (https://www.medrxiv.org/content/10.1101/2022.07.06.22277306v1). It’s hard to say how soon reinfections can occur, because this depends on so many things like strength of immunity, the infecting variant, the type of variant that you have immunity against, etc. It can also be hard to detect a reinfection – it is just residual virus from the first infection or is it a true new infection? Importantly, vaccination in addition to other non-pharmaceutical interventions are still effective at minimising the risk of reinfection."

Does having having COVID-19 more than once bring further risks or conditions (sequelae)? If so, what are they?

"Every time you are infected with COVID there is a risk of developing sequelae that can linger for weeks, months, or longer.

These sequelae include: pulmonary disorders, neurologic disorders, mental health disorders, functional mobility impairments, difficulty concentrating, generalised anxiety, generalised functional impairments, fatigue, muscle weakness, cardiac disorders, dermatologic disorders, digestive disorders, and ear, nose and throat disorders (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784918).

The risk of post-acute sequelae of COVID-19 (PASC) or ‘long COVID’ have been shown to be lower in vaccinated individuals (https://www.nature.com/articles/s41591-022-01840-0, https://www.medrxiv.org/content/10.1101/2022.01.05.22268800v2.full.pdf). In addition, vaccines lower the risk of being infected in the first place (https://www.nature.com/articles/s41467-022-30895-3).

Therefore, the most effective way to minimise your risk of ‘long COVID’ is to minimise the risk of getting infected or re-infected by getting vaccinated and using other non-pharmaceutical interventions."

https://www.theatlantic.com/health/archive/2022/05/covid-reinfection-research-immunity/639436/

https://www.webmd.com/lung/what-is-long-covid-pasc#1

Restrictions and activities:

With governments reluctant to re-introduce restrictions such as mask mandates, what is the best way for people to avoid Covid this winter?

"Vaccination in addition to other non-pharmaceutical interventions are still effective at minimising the risk of infection and reinfection. Non-pharmaceutical interventions include: masking (ideally with a P2/N95/KN95 mask), social distancing, minimising the number of social contacts, choosing outdoor activities over indoor activities, ensuring adequate ventilation, using air filters if possible, maintaining general health (sleep, exercise, eating well)"

Should we be considering another lockdown? Why/Why not?

"We should clearly communicate that the COVID-19 pandemic is not over and Non-pharmaceutical interventions as explained above are key to reduce infections in Australia. Globally we need a comprehensive vaccination strategy for EVERYONE to reduce the risk of the constant emergence of new variants.

Overall the questions of new lockdowns is misplaced. There are many other interventions that are proven to be successful but are not implemented at the moment. These should be implemented first."

Vaccines:

Are the vaccines less effective against these new variants and if so, what benefit does the fourth dose bring?

"Boosting our antibody levels through a fourth dose ensures that we are maintaining high levels of antibodies to be able to rapidly neutralise any virus particles entering our body. While vaccine antibodies may be *less* effective at neutralising newer variants of SARS-CoV-2 compared to the ‘original’ variant, they are still effective, and having more antibodies around will maximise our protection.

Studies from Israel have shown that the fourth dose is very good to prevent serve illness and death in people above 50 and people with other risk factors. Hence a fourth dose is an excellent idea at the whole population level when targeted to older age groups.

Importantly, other non-pharmaceutical interventions further minimise the risk of infection/reinfection."

As a virologist BA5 is certainly the most interesting of the Omicron family. We have looked at BA5 here in the lab.

To sum up what we see. Antibodies in the community (from vaccination or vaccination + infection) still bind and block the virus but at levels lower than the earlier variants (which is typical for Omicron in general). This laboratory observation helps determine if those who have been vaccinated at least 3x will be protected from severe disease & from our observations and others, vaccines once again will help with the BA5 wave.

So the advice from ATAGI regarding the benefit of booster shots is still a very important message to get out, is still applicable for BA5 and they summarise this very well.

So what is driving the wave and why would we worry then? We are seeing a signal that BA5 can infect our body a little differently than its other Omicron relatives. From what we see it can infect in a manner that is similar to pre-Omicron variants. So in brief it can have the benefit of its parent BA2 (great at transmission and very slippery to existing antibodies) but also has expanded its options into what cells it likes. We see this as it uses a protein called TMPRSS2 better and use of that protein increases its efficiency of infecting cells lower in the respiratory tract (lung). Other Omicrons didn’t do that so well. This one does. 

In animal models disease severity is higher and the lung is more of a viral target. This is consistent with what we see in how the virus enters cells. That said, animal models do not take into account prior viral infection and/or vaccination (what we see in the community).
 
How it will manifest globally we are all watching closely.  In countries with high vaccine uptake (especially third shots) and/or high levels of previous infection, the disease severity will be tempered. 
 
Whilst the wave will hopefully be tempered, protecting those at risk will be key (elderly and immunocompromised) and whilst they can wear a mask, the rest of us can also help by doing the same when numbers accelerate.

There are many subvariants of Omicron, such as BA.1, BA.2, BA.3, BA.4, BA.5 and descendent lineages. New BA.4 and BA.5 variants of Omicrons seem more infectious compared to their predecessors, however there is no evidence that they are more virulent as well. The recent increase in number of deaths is due to the high number of cases. So, we need to avoid large outbreaks. 

Centaurus is the nickname of another variant of Omicron (BA.2.75 variant) and currently there is limited data on this new variant. Cases are reported from India, UK and some other countries. The large number of mutations in Centaurus is concerning, however more data is needed before we jump to any conclusion. The WHO is also closely monitoring the new variant and has not yet declared it as variant of concern (VOC). 

It is believed that new Omicron subvariants (e.g. BA.4 and BA.5) can escape from the immune system and can cause re-infection. Some recent data suggests that re-infection is occurring early, that's why Australia and some other countries have reduced the reinfection period from 12 week to four weeks. At this stage we do not know whether re-infections cause more severe illness or symptoms. We know that vaccinated people have less severe outcomes and fewer deaths, so it may be postulated that re-infection may be less severe. However, as said, more data is needed. 

I think we should adopt a precautionary approach and continue using available control measures to avoid large outbreaks. Large outbreaks will not only result in more deaths, but will also overwhelm the heath system.  If a universal mask mandate is not possible for the next few months, then it may be introduced at crowded (e.g. public transports, shopping centres, large gatherings etc) and high risk (e.g. hospitals, aged care etc) places. This will also avoid other unwanted measures such as lockdowns. We are still not out of the pandemic and new variants are emerging, so we cannot be complacent. Though vaccines are less effective against these new variants, we should still promote vaccines as they are safe and still preventing hospitalisations and deaths. Most deaths are still among unvaccinated and in people without booster doses.

There is emerging evidence that BA 4/5 strains are spreading faster through the population. That could be for two reasons: either inherent transmissibility, or immune escape. For this variant, we believe almost all of the advantage to be due to immune escape.

In the UK, we’re seeing people who have a good level of immunity (through either vaccination or infection) being infected more often. And in Australia, with our very high vaccination coverage, we’re seeing case numbers rise.

Immune evasion basically means the antibodies we’ve developed aren’t as effective in neutralising the virus. It doesn’t mean we have no protection at all, just that the protection we do have is less than previously. Having 6 weeks between infections now seems quite plausible. We’ve seen the Victorian government reduce the time before re-isolation of positive cases in line with this observation.

On vaccines, the fourth dose doesn’t give as big of a boost as third doses did. But it does ‘reset the clock’ on our immunity, bringing people back to slightly above third dose protection. As we go into the higher risk winter season, this extra immunity could be valuable for people.

While mandates don’t seem to be being looked for right now, that doesn’t mean the behaviour is out of the question. The best way to avoid COVID-19 is still to be vaccinated, wear a mask, meet outside and keep your distance wherever you can.

Are the new variants managing to evade the immune system? What does this mean?

"Broadly there are hundreds of variants of the virus. Some die out before they have an opportunity to infect others and never take hold in the community and others do, such as Delta, Omicron etc. Just because your immune system recognises one variant through vaccination or that you have had a variant of the virus, doesn’t mean your immune system can recognise another variant even though they may be similar. This is no different to the influenza virus, where there are also many variants which is the reason why you need to be vaccinated every year."
 
After COVID-19, how soon should people consider themselves at risk of getting it again and how severe are reinfections likely to be?

"Immunity seems to last for a few months. However as there are many variants the concept of ‘protected’ isn't really something to rely on. We should always use universal precautions to prevent contraction of the virus including making sure we are vaccinated, mask-wearing in populated places, hand sanitising, keeping in well-ventilated areas. What vaccination does very effectively is reduce the possibility of death and severe disease to a minimum."

With governments reluctant to re-introduce restrictions such as mask mandates, what is the best way for people to avoid COVID-19 this winter?

"Stick to the basics making sure you are recently vaccinated, mask-wearing in populated places, hand sanitising, keeping in well-ventilated areas. Then there are the usuals, keeping warm, good diet etc."

Should we be considering another lockdown? Why/Why not?

"As hospitalisations go up with an ever-stretched hospital workforce, the only way to decrease hospitalisations is to decrease transmission or reduce the severity of the virus with vaccination and antivirals. The reason for this is that COVID-19 has a mortality and morbidity associated with it. They are linked. If numbers go up so does mortality and hospitalisations and vice versa. We have to have a clear policy on how many cases our system can handle and then use the various options to prevent cases going beyond this in the medium and long term."
 
Are the vaccines less effective against these new variants and if so, what benefit does the fourth dose bring?
 
"The current vaccines are effective to the new variants for prevention of severe disease and mortality. That being said they are less effective for prevention of becoming infected with the new variants. That is no reason to not have the fourth dose as vaccination is still effective. The influenza vaccines get modified as new variants present. It is no different. I am sure there will be a time when there is a combined influenza SARS-COV2 vaccine." 
 
"We know this virus has a mortality and morbidity associated with it. Therefore if you increase transmission and more people contract the virus, more people will die and more people will be in hospital. You have to look at the both sides of the equation when making comment abouts about masks, social distancing etc. Currently hospitalisations are far too high for our health system. Policies centring on transmission need to be considered."

Is there evidence that the BA 4/5 strains are more virulent and more infectious?

"No more VIRULENT. That is, as best we can tell, if you are infected with BA 4/5, your chance of serious illness is much the same. However, there is a pattern of higher hospital counts as a ratio to case counts around Australasia of late. I suspect this is more that notification rates are falling away (e.g. about half of all infections seemed to be notified a month or so ago, and it might now be less than half), meaning the ratio of people in hospital to notified cases is driven higher. 

Yes, it is more INFECTIOUS. Probably all/mostly due to immune escape (i.e. less protection from vaccines and previous infection with previous variants), than due to innate increase in infectiousness (i.e. an innate increase in the R0))."

Are the new variants managing to evade the immune system? What does this mean?

"Yes - Randomly occurring mutations that – by chance – make the virus less detectable and ‘attackable’ by our immune system have a survival advantage. And take over. This evolution is to be expected, and one of my colleagues has termed it the “dazzling Darwinian dance”."

Are people becoming re-infected more quickly and if so, why?

"Immune escape means that the window of protection is less."

After COVID-19, how soon should people consider themselves at risk of getting it again and how severe are reinfections likely to be?

"How long is a piece of string? More thoughtfully:

• You would be extremely unlucky to be re-infected within months by the same variant. So if you had a BA 4/5 infection, your chance of being re-infected in the next few months is low – not zero, but low. In our modelling, we assume that chance is half that from being vaccinated (i.e. natural infection is a bit better at protecting you from the same variant than vaccination).
• But let's imagine BA.6 turns up. And it is substantially different from BA 4/5. Then, in theory, your chance of being infected with BA.6 if you have recently been infected with BA 4/5 is real. We strongly suspect your last BA 4/5 infection will offer you some protection, but not full protection." 

Does having COVID-19 more than once bring further risks or conditions (sequelae)? If so, what are they?

"There are two types of long risk: Long COVID-19, and increased rates of other diseases (like heart disease and dementia). To the best of my knowledge, you do not have a markedly increased risk of either from repeat infection, over and above one infection. But data is not yet ‘in’ on this; time will tell. What we can more confidently say is that your chance of long COVID-19 from an Omicron infection is half that from a Delta (or earlier variant) infection. Being immunised reduces the risk of long COVID if infected by 75%. Thus, if you are vaccinated and get Omicron, your chance of long COVID is 1 – (1-50%).(1-75%) = 87.5% less than your chance of long COVID when you were unvaccinated and infected with a pre-Omicron variant. So that is good."

With governments reluctant to re-introduce restrictions such as mask mandates, what is the best way for people to avoid COVID-19 this winter?

"Keep up to date with your boosters, wear masks (preferably N95) in indoor settings outside the home, work from home if practicable."

Should we be considering another lockdown? Why/Why not?

"No. We are far more resilient now due to previous infection and vaccination. To avoid overwhelming health systems in the next 2 months, we do want to:

• Encourage those eligible for a third dose who have not had one to go get one (about 25% to third of the adult population!).
• Encourage those now eligible for a fourth dose (second booster) to go get one.
• Enforce mandatory mask wearing on public transport (compliance is poor at the moment!).
• Encourage people to voluntarily wear masks (preferably N95) indoor settings outside the home.

If these actions are not enough to stop health systems getting overwhelmed, then we may need to step up some mandatory measures."  

Are the vaccines less effective against these new variants and if so, what benefit does the fourth dose bring?

"The fourth dose returns you to your immunity level (or a bit higher) than that after your third dose. This was really good for earlier variants! For Omicron BA 4/5, it is not great, though, or your risk of any infection. We do not know exactly the vaccine effectiveness yet. But my educated guess is that in the month or two after your fourth dose, you are probably 50% or so less likely to get BA 4/5 than if you were completely unvaccinated. Which is not great, but still useful for dampening transmission in the community. HOWEVER, we are very confident that your protection against serious illness after a fourth dose will be nicely boosted – so get your fourth dose if eligible.