1. Efficacy means “[the body] can produce IgM and IgG [antibodies]” and not “effective against COVID”. How long will antibodies remain in vaccinated patients (2 injections)?

Efficacy determined in phase III trials of vaccines actually means “effective against symptomatic COVID-19”. Antibodies in vaccinated patients (Moderna mRNA vaccine) definitely persist for ~ 4 months after vaccination. Longer-term follow-up data on vaccinated patients is pending.

2. Does IgA provide better protection against infection than IgG?

High levels of mucosal IgA potentially provide better protection against upper respiratory tract COVID-19 infection, although IgG is also important in the lower respiratory tract. Some COVID-19 vaccines like the Chimpanzee adenovirus vector vaccines can generate circulating IgA in addition to IgG. Detailed immunological analysis of people vaccinated with other platforms is pending.

3. Please comment on “Pathogenic Priming” of COVID infection with vaccination, making infection by native COVID (mutant strain, especially) more severe and may precipitate an uncontrollable cytokines storm. It has been documented that the same person can be infected with different strain of COVID coronavirus and may lead to death.

Inactivated/ mRNA/ adenovirus vector vaccines have shown good efficacy against severe COVID-19 in phase III trials, indicating that such priming is not taking place. It is notable that most vaccines were developed for D614 virus, but were evaluated in D614G endemic areas suggesting that spike mutants so far do not appear to affect vaccine efficacy adversely.

4. A [natural] COVID infection can cause spontaneous resolution of lymphoma (BMJ). Will COVID vaccine[s] have the same function?

Clinical experience of COVID-19 in hematological malignancy does not suggest that this type of remission is a common or consistent effect. Therefore, it is unlikely that vaccines would cause spontaneous resolution of underlying malignancies.

1. [Is it] safe and effective to receive different brands of COVID 19 vaccine? Will different COVID vaccines affect immunogenicity? i.e. Using mRNA then [inactivated] vaccine, or vice versa.

This is unknown at this stage and not recommended. It is not advisable to mix different types of vaccines, especially belonging to different platforms (e.g. inactivated virus and mRNA) as their immunostimulatory mechanisms are very different with unpredictable consequences upon mixing.

2. Any use for extra doses? Meaning more than 2 doses or more frequent doses, would it help to improve efficacy?

So far, two doses at initial exposure appears reasonably effective. Adding a third dose would be prohibitively expensive and also slow down vaccination rollout. It is possible that occasional boosting may be required for vulnerable individuals like the elderly. But we need a better understanding of the durability of protection of two vaccine doses to make this call.

1. How should I choose my COVID-19 vaccines?

The choice of vaccines a personal one as different vaccine types have differing advantages and disadvantages. The higher efficacy of mRNA vaccines come with more local side effects and some fever. There is also a higher risk of allergy than other vaccine types. The inactivated vaccines appear quite safe with mild local side effects, but the overall efficacy against symptomatic COVID-19 appears to be lower.

2. Will it be likely that we shall need annual vaccination?

This might be the case for vulnerable groups, but it is unlikely that the entire population would require repeated annual vaccination.

3. What will happen to the whole population of HK if 1 million people receive a 50% efficacy COVID vaccine? What will happen to an individual who has that vaccine?

From an individual perspective, this means that they are 50% less likely to have symptomatic COVID-19 and probably very unlikely to have severe COVID-19. It is possible that current vaccines do not confer sterilizing immunity i.e. vaccinated persons may still develop silent infections that are transmitted onwards. This means that there may still be COVID-19 outbreaks if only 1 million HK people get the vaccine. We need much higher vaccine rates to reduce the chance of outbreaks and waves.

1. Is there any risk of [vaccinations] affecting fertility?

No indication of this so far.

2. Any increased risk of antibody-dependent enhancement issue?

No evidence that this is occurring.

3. What [are the risks] of having a 50% efficacy vaccine affect adversely [those] subsequently receiving other types of [COVID vaccines]?

This is unknown at this stage and not recommended. It is not advisable to mix different types of vaccines, especially belonging to different platforms (e.g. inactivated virus and mRNA) as their immunostimulatory mechanisms are very different with unpredictable consequences upon mixing.

1. Do you recommend vaccinating cancer patients currently on immunotherapy?
2. Wil the vaccine precipitate/cause relapse/worsening of autoimmune disease? Did the Pfizer & Modena vaccine study include this group of patients?
3. [What if a patient is on biologicals] like TNF or Interleukin ab? Must [it] be mRNA?

Combined answer: the clinical trials did not include vulnerable immunocompromised patients. Therefore, the efficacy and safety profile of vaccines in these patient groups is unknown. Generally, mRNA vaccines and inactivated vaccines don’t contain ‘live’ virus, so they are theoretically safe. There is no evidence so far that mRNA vaccines can cause flares of autoimmune diseases. Efficacy of vaccines in these groups can be assumed to be lower than the general population, but would still be useful as this group is also at risk of severe COVID-19. Vaccination of such patients should be offered with adequate patient counselling. For example, such patients should continue to wear masks and practice social distancing even after receiving the vaccine due to unknown efficacy.

4. AZD1222 contains ethanol as an excipient. For those who are allergic to alcohol, are they contraindicated for the vaccine?

Depends on the type of allergic reaction, but usually I would recommend getting a vaccine without ethanol as an excipient.

1. [Comment on the Oxford/AstraZeneca SD/LD paradox] The reason is that a higher dose of AZD1222 causes a quicker immune reaction, attacking the adenovirus before it allows introduction of DNA in production of spike protein, hence this is the reason why it is less effacious. Also, the shorter dose is by accident.
   The adenovirus load is bigger, causing a bigger immune reaction, before introduction of DNA into the cells for production of S protein of SARS-CoV-2.

This is one of the hypotheses but the exact reason for LD/SD being superior to SD/SD is unknown. It is also unclear whether this is a genuine effect due to other possible confounders in the trial. Further evidence is required to confirm this phenomenon.

2. Why was Sinopharm not included in the government purchase? Any idea?

Sinopharm is also an inactivated vaccine, so the government decided not to purchase two vaccines belonging to the same vaccine platform.

3. Is the Pfizer vaccine essential same as BioNtech?

Yes.