COVID-19 vaccines — light at the

Over the past few months, the world has witnessed a resurgence of COVID-19 cases after a period of quiescence in the summer months.

Currently much of western Europe and the United States are seeing increasing numbers of COVID-19 cases, hospitalisations, and deaths. The past three weeks have, however, brought some good news as results of three phase three trials of COVID-19 vaccines have been announced. This week we will look at these three trials and see what the implications are for future management of the epidemic.

PFIZER/BIONTECH VACCINE

The first company to report results was Pfizer, who are working in conjunction with a German company Biontech. Their phase three study included approximately 43,000 people who were divided into a vaccine group and a placebo group. The vaccine group received two doses of vaccine approximately three weeks apart. They then looked for symptomatic COVID-19 disease. There was a total of 170 cases of which 162 occurred in the placebo group and only eight occurred in patients who had been vaccinated. This suggests an efficacy of 95 per cent.

Remarkably, of the total number of 10 individuals who had severe COVID-19 disease, only one was in the vaccine group. This suggests that the vaccine reduces symptomatic COVID-19 infections but also reduces the severity of infection in those who do become infected. The incidence of side effects was low with fatigue and headache occurring in two per cent and 3.8 per cent of placebo and vaccine recipients, respectively.

The major downside of the Pfizer vaccine is the storage requirement. The vaccine must be kept at -70 Celsius which does require specialised refrigerators which are usually only found in research facilities or large academic hospitals. In the developed world this is quite challenging, and for most low and middle-income countries this represents a significant obstacle to use.

Pfizer has been granted emergency approval in the United Kingdom with vaccinations starting in the second week in December. The company estimates that they can produce 50 million doses this year and 1.3 billion doses next year. It is unlikely that any of the early doses would be available to any of the low and middle-income countries like Jamaica as many of the richer countries have prepaid for the orders.

NIH/MODERNA

The second successful vaccine candidate is produced by Moderna in conjunction with the National Institutes of Health (NIH) in the United States. Their study had approximately 30,000 patients divided into vaccine and placebo groups. The vaccine group received two doses four weeks apart. Like the Pfizer group they were looking for a reduction in symptomatic COVID-19 cases.

Currently they have found 196 cases of COVID-19 of which 185 were in the placebo group and 11 in the vaccine group giving an efficacy of 94.1 per cent — 30 severe cases and one death were noted, all in the placebo group. Side effects were mild and infrequent.

The results suggest an effective vaccine for preventing symptomatic COVID-19 disease and like the Pfizer vaccine, a reduction in the likelihood of severe disease in the patients who do get symptomatic infection. An advantage of the Nih/moderna vaccine is the fact that it can be stored at -20 degrees C (which is the standard freezer temperature). More recent data has suggested that it can be kept at 2-8 degrees Celsius (which is the normal refrigerator temperature) for up to seven days.

Currently, they have applied to the US Food and Drug Administration (FDA) for emergency approval. They estimate the ability to produce 15 million doses this year and 500 million to one billion doses in 2021. The Moderna vaccine development has benefited from support from the US Government and it is to be expected that most of these early doses would be reserved for the USA where the pandemic has witnessed an unprecedented surge.

ASTRAZENECA/OXFORD VACCINE

The last vaccine is from Astrazeneca which was developed in conjunction with Oxford University. They studied 23,000 patients in two sub studies in Brazil and England. The vaccine group was intended to receive two doses of the vaccine four weeks apart. They reported a total of 131 cases of symptomatic COVID-19 disease. The overall efficacy of the vaccine is reported to be 70 per cent with no cases of severe disease or hospitalisation in patients who received the vaccine.

The interpretation of the study is somewhat challenging as a production error resulted in a subset of patients receiving half of the intended dose for the initial vaccination. Surprisingly, this group had the highest efficacy overall of 90 per cent. The vaccine group patients receiving the intended dosing schedule had an efficacy of 62 per cent. The average of these two dosing regimens gives the overall 70 per cent efficacy. The reasons for the higher efficacy with lower initial dosing remain unclear and further data is being gathered in the US arm of the study. A recent article in the respected journal Lancet has also raised some questions concerning the vector for this vaccine based on past experiences. It is a development we are monitoring and will highlight in subsequent columns if it becomes necessary.

While the efficacy is not as good as the Pfizer/biontech and the Nih/moderna vaccines it does meet the 50 per cent benchmark that is required for approval. In addition to the data on symptomatic COVID-19 infection, the Astrazeneca group did weekly nasal swabs on study participants providing data on asymptomatic infection and transmission. Given this data it is the only vaccine that has shown that it can reduce COVID-19 spread in addition to reducing symptomatic and asymptomatic infection.

Other advantages of this vaccine are the facts that it can be stored at 2-8 degrees Celsius (normal refrigerator temperature) and that the cost is likely to be in the range of 3 to 5 US dollars. They estimate production of 300 million doses by the end of March 2021 and the ability to produce 200 million doses per month subsequently. They have submitted data to the regulatory authorities in the United Kingdom for approval.

It appears that with the initial results of the above, the three companies we are about to take a significant step forward in the management of the COVID-19 epidemic. It does remain unclear how long the vaccines offer protection and whether repeat dosing will be required but there will be follow up data for two years after vaccination. We will need either additional successful vaccine candidates or a significant Madu