The Janssen COVID-19 vaccine

Clinical trials of the Janssen COVID-19 vaccine (in some parts of the world this is called the Johnson & Johnson COVID-19 vaccine) have found that it is generally safe. Common side effects included pain at the injection site, headache, fatigue and muscle soreness. These side effects were generally mild and temporary. Furthermore, they suggest that the immune system is responding to the vaccine. The vaccine was 66% effective at reducing the risk of developing COVID-19 after one injection. Leading scientists and public health officials in Canada, the European Union and the U.S. have noted the following:

Although there may be a risk of developing blood clots with this and other COVID-19 vaccines, the risk is generally very small compared to the much greater risk of developing COVID-19 and requiring hospitalization if one is not vaccinated.

The Janssen vaccine is based on a modified adenovirus. For further information about how adenoviruses are used as vaccines, please see the previous article about adenoviruses in this issue of TreatmentUpdate.

Study details

Janssen conducted a phase III clinical trial of its vaccine in about 40,000 people. Participants were randomized to receive one of the following interventions:

• a single intramuscular injection of the vaccine into the upper arm
• a single intramuscular injection of placebo into the upper arm

The average profile of participants upon study entry was as follows:

• 55% men, 45% women
• age distribution: 18 to 59 years – 65% of participants; 60 and older – 35%; 65 and older – 20%; 75 and older – 4%
• major ethno-racial groups – 62% white, 45% Hispanic, 17% Black, 8% Indigenous, Asian – 4% (due to the overlap of ethno-racial categories, the total proportion does not equal 100%)
• presence of one or more underlying conditions (comorbidities) – 40%

Focus on comorbidities

Participants had a wide range of comorbidities. The four most common were as follows:

• obesity – 29%
• high blood pressure – 3%
• HIV infection – 2%
• asthma – 1%

Results

Before the data were analyzed, participants were monitored for about two months post-vaccination.

Cases of flu-like symptoms that occurred at least 28 days after vaccination and that tested positive for SARS-CoV-2 (via analysis of nasal swabs) were distributed as follows:

• vaccine – 66 cases of COVID-19
• placebo – 193 cases of COVID-19

According to calculations by the U.S. Food and Drug Administration (FDA), the vaccine was 66% effective in reducing the risk of moderate-to-severe COVID-19.

Hospitalizations

Beginning 14 days after vaccination, the numbers of people hospitalized were distributed as follows:

• vaccine – 2 people
• placebo – 29 people

There were no further cases of hospitalization among people who received the vaccine. However, among people given placebo, further cases of hospitalization occurred beyond the initial 14-day analysis. No one who was vaccinated died from complications arising from COVID-19. However, seven people who received placebo and who developed COVID-19 and who were hospitalized died.

Demographics

There was no significant impact of the following factors on the effectiveness of the vaccine:

• age
• comorbidities
• ethno-racial groups

Adverse effects

Common side effects were as follows:

• pain at the injection site – 49%
• headache – 39%
• fatigue – 38%
• muscle ache – 33%

In general, these were more common in younger than older people.

The above-mentioned side effects were generally very mild and temporary. In most people they appeared within a day or two after vaccination and resolved within a couple of days.

Clotting-related events

There was a slight imbalance in the distribution of excess formation of blood clots, as follows:

• vaccine – 15 clots in 14 people (0.06%)
• placebo – 10 clots in 10 people (0.05%)

Readers can see that excess clot formation normally occurs in a population but at very low rates. It is not clear how many people who received the vaccine would have developed excess blood clots had they not been vaccinated. However, clotting problems that may be associated with this vaccine are likely very rare.

These clots occurred in different parts of the body—limbs, lungs, carotid artery, hemorrhoids. Most participants affected in the vaccine group were male (12 men vs. two women). The clots were generally associated with only a modest degree of injury and everyone recovered or is recovering. The age range affected by the excess clots among vaccinated people was between 25 and 90 years. An FDA analysis suggested that many of the affected participants were at heightened risk for excess blood clots due to underlying issues. Furthermore, in all but one case of blood clots that occurred in vaccinated persons, investigators concluded that the clots were unrelated to the vaccine.

Here are details on the only case where investigators concluded that the clots were related to vaccination:

A 52-year-old male with obesity (his body mass index was 32.4 kg/m²) developed pain in one of his calves 27 days following vaccination. An ultrasound scan revealed the presence of a blood clot in his calf. He was diagnosed with deep vein thrombosis. According to the FDA, investigators considered this issue “non-serious” but related to his vaccination. However, Janssen disputes any relationship with its vaccine and the subsequent development of blood clots in this man.

A future issue of TreatmentUpdate will explore the topic of blood clots that have occurred in very rare cases with COVID-19 vaccines.

Hypersensitivity reactions

There was one report of a hypersensitivity reaction (a kind of allergic reaction) that occurred in a person two days after vaccination. This was not fatal and no further details were provided.

Pregnancy

As with many large COVID-19 vaccine studies, women of childbearing potential were screened for pregnancy prior to randomization. Those who tested positive were excluded from the study. However, once vaccinated, some women in these and other COVID-19 vaccines studies may become pregnant.

Two women in the vaccine group in the Janssen study are currently pregnant and the results of the pregnancy are not known.

Experiments with rabbits before, during and after pregnancy found no harmful effects on the pregnant rabbits or their offspring when they were given the same dose of the vaccine used in humans.

Vulnerable populations

There were relatively small proportions of people with HIV infection—about 3%. HIV-positive participants would have been on treatment (ART) and healthy and well. No results of the vaccine in this population were released.

About 0.5% of participants were categorized as having an unspecified liver disease. It is possible that some of them had viral hepatitis, but at this time the company has not released details.

For the future

Janssen is conducting another large study in which two injections of the vaccine are given. Results from this study are expected later in 2021. The company is also planning other studies.

—Sean R. Hosein

REFERENCES:

1. Food and Drug Administration. Janssen Ad26.COV2.S Vaccine for the prevention of COVID-19. FDA Briefing Document. 26 February 2021.
2. European Medicines Association. COVID-19 Vaccine AstraZeneca: PRAC investigating cases of thromboembolic events—vaccine’s benefits currently still outweigh risks – update. Press release. 11 April 2021.
3. Food and Drug Administration. Joint CDC and FDA Statement on Johnson & Johnson COVID-19 Vaccine. 13 April 2021.
4. COVID-19 Vaccine Janssen: assessment of very rare cases of unusual blood clots with low platelets continues. Press release. 14 April 2021.