Updates on boosters and treatments, and how these may help against Omicron

CLINICAL MATTERS

As more Omicron cases are reported in returning travelers, the possibility of breakthrough community transmission becomes greater and greater. It will likely be just a matter of time before this occurs. When it does happen, a growth rate faster than Delta’s is expected based on the European and American experience. Omicron has rapidly become the dominant variant in the US, even in competition with Delta.  

There is increasing epidemiologic and laboratory evidence that Omicron may cause less severe disease than Delta. In laboratory experiments, Omicron is more likely to infect the lining of air passages but it is less efficient at multiplying when it reaches the lungs. More viral particles in the airways may result in higher contagiousness, while less viral particles in the lung tissue mean less damage to the lungs. 

In Gauteng province in South Africa where the first Omicron outbreak was reported, there is now a downtrend in cases after an initial exponential increase of cases. Hospitalizations were significantly less compared with its Delta wave. In the US and Europe, Omicron cases continue to rise in record numbers. Even if Omicron is associated with milder disease, the sheer number of sick people can still overwhelm the healthcare systems. 

Omicron is associated with higher breakthrough infections among fully vaccinated and previously infected individuals. It is therefore essential that masks and other preventive measures continue to be used even in places with high vaccination rates in order to slow down the rate of infection. Unvaccinated individuals are still at highest risk for severe disease and death, so primary vaccination is more essential than ever.

The latest on boosters

A recent review from the World Health Organization discussed the use of boosters. This included which boosters to use, and which vaccines can be safely mixed with each other. Homologous strategies use the same vaccines as an additional dose. Heterologous strategies use a different brand or platform of the vaccine.

From a purely safety standpoint, WHO recommends homologous boosters. A third dose of the same vaccine is more predictable, especially if there were no problems with the first two doses. There is some evidence of more intense side effects though not necessarily severe with mixing vaccine brands. For frail individuals who may not be able to tolerate increased side effects, a homologous strategy may be the safest option. 

There is some data that boosting as early as three months from the second dose results in higher antibody generation for heterologous boosters, although this doesn’t necessarily translate to better clinical protection. Based on multiple studies, the following combinations may be associated with better efficacy, but it is uncertain by how much they decrease the risk of infection.

1. Boost inactivated vaccines (Sinovac or Sinopharm) with mRNA vaccines (Pfizer or Moderna) or vector vaccine (Astra). The WHO review shows that boosting inactivated vaccines with mRNA vaccines has the highest efficacy compared to other platforms. A separate study from Chile, however, shows that while Sinovac boosted with Sinovac, Pfizer, or Astra should all protect against severe disease, the best overall protection is seen with an Astra booster. Combining these findings, either vector (Astra) or mRNA (Pfizer or Moderna), is okay to use as a booster. The one with the least side effects may still be a third dose of inactivated vaccine, which can still provide a good amount of added protection, but it won’t be as high as the other two.

1. Boost vector vaccines (Astra, Janssen, Gamaleya) with mRNA vaccines (Pfizer or Moderna). Using a homologous strategy with vector vaccines carries a theoretical risk of decreasing efficacy since repeated use of a vector causes antibodies to develop against it. This results in the body destroying the vector in subsequent doses of vector vaccine before it can induce an immune response against SARS-CoV-2.

1. Boost mRNA vaccines (Pfizer or Moderna) with vector vaccine (Astra only in the Philippines) or with a homologous strategy. The use of a vector vaccine booster for mRNA is a new finding based on the WHO review. A more recent paper shows that homologous mRNA vaccination offers similar protection to mRNA boosted with a vector vaccine, but this study was not included in the WHO appraisal. Either homologous or heterologous strategies seems to have some benefit for mRNA, and so either approach is viable. A preference may emerge when more data is available. Pfizer and Moderna   mRNA vaccines have been linked to a very small increased risk of myocarditis, or inflammation of the cardiac muscle. The overall risk is low and getting COVID-19 infection is still several times more likely to cause myocarditis than vaccination. For those with a history of heart problems, however, it might be prudent to avoid these types of vaccines. Vector vaccines (Janssen, Gamaleya, Astra) are linked to a small increased risk of blood clots. This risk is also much lower compared with the risk of blood clots from natural COVID-19 infection. If someone has a history of blood clots, avoid these types of vaccines. Inactivated platforms (Sinovac, Sinopharm) remain the safest COVID-19 vaccines.

Current Philippine guidelines only allow the use of one of four vaccines for boosting (Sinovac, Pfizer, Moderna half-dose, Astra) so these are what are available at the moment.  Only one booster shot is allowed at this time, and there is currently no evidence that additional booster doses add more protection. The Emergency Use Authorization (EUA) for the timing of boosting was just recently amended. From giving boosters at least six months from the second dose, the EUA was revised to giving boosters at three months from the second dose. The exception is Janssen, which is a single-dose vaccine. An mRNA booster after a first Janssen dose may be given after two months, which was previously set at three months. These are continuously being reviewed and may change. 

For now, WHO prioritizes primary vaccination (those who haven’t gotten their first two doses) because this will save the most lives than boosting, especially if vaccine doses are limited. Protection against severe disease continues even without boosting and this protection goes beyond six months. Boosters should be prioritized for the most vulnerable if there is scarcity. 

The latest on treatment

Molnupiravir finally got an EUA from the Philippines FDA. The shine on this drug has decreased a bit since a reanalysis of data showed that its ability to decrease the risk of hospitalization among high-risk patients with mild disease went from 50 percent to 30 percent. As it is the first proven oral drug to work against COVID-19, it will still be useful and will save lives. The EUA states that it is for use only in those with a positive COVID-19 test. It is not meant for prevention or prophylaxis, and can be harmful if misused.

Paxlovid (nirmatrelvir + ritonavir) was recently approved in the US. Like molnupiravir, it is an oral treatment for proven mild COVID-19 in high-risk patients. It decreases the risk of hospitalization and death in the target population by 89 percent. Similar to molnupiravir, it is not meant for prophylaxis.

Remdesivir, one of the first anti-COVID-19 drugs used for severe disease, has now been shown to reduce the risk of hospitalization in high-risk patients with mild COVID-19 by 87 percent. This reduction is very similar to Paxlovid, although the major difficulty for remdesivir is that it needs to be administered intravenously. Nevertheless, since it is already familiar to most physicians treating COVID-19, it can have a major impact while waiting for Paxlovid to arrive.

Overall, the recent news for COVID-19 is promising. Vaccination and treatment are working, but masks remain essential. Next-generation and reformulated vaccines are on the way, but boosters and new treatments can mitigate the risk from Omicron while waiting. The choice of booster ultimately depends on balancing the potential added benefit of a heterologous strategy, versus the safety of a homologous one. When in doubt, this decision is best discussed with your physician.