COVID-19 Vaccine Safety Now: Soft Rollout, Not Pause, After Reports Of Guillain-Barré Syndrome

Johnson & Johnson’s COVID-19 vaccine has been associated with a small risk of Guillain-Barré syndrome, but unlike with its link to rare incidents of blood clots, the US Food and Drug Administration and Centers for Disease Control and Prevention are not requesting a pause in the administration of the shot.

The CDC issued a statement on 12 July noting that the CDC and FDA are monitoring reports of Guillain-Barre syndrome after receipt of J&J’s vaccine, distributed by its Janssen unit. Around 100 preliminary reports of GBS have been detected in the Vaccine Adverse Events Reporting System (VAERS), which is co-managed by CDC and FDA, after 12.8 million doses of the J&J vaccine were administered.

“These cases have largely been reported about two weeks after vaccination and mostly in males, many aged 50 years and older,” CDC stated. “Available data do not show a similar pattern with mRNA vaccines (Pfizer-BioNTech and Moderna), after over 321 million doses administered in the United States.”

In a separate statement, the FDA said that of the 100 preliminary reports, 95 of them were serious and required hospitalization and there was one reported death. "Although the available evidence suggests an association between the Janssen vaccine and increased risk of GBS, it is insufficient to establish a causal relationship," the agency stated. "Importantly, the FDA has evaluated the available information for the Janssen COVID-19 vaccine and continues to find the known and potential benefits clearly outweigh the known and potential risks."

CDC’s Advisory Committee on Immunization Practices (ACIP) will discuss the reports of GBS at an upcoming meeting, the date of which is yet to be announced.

There is a notable contrast between the approach the health agencies took with the reports of Guillain-Barré syndrome and the reports that the J&J vaccine was associated with cases of cerebral venous thrombosis in combination with low levels of platelets.

On 13 April, the FDA and CDC called for a pause in administration of the J&J shot after six reported cases of cerebral venous thrombosis in combination with low levels of platelets, including one death, in women between the ages of 18 and 48. (Also see "J&J COVID-19 Vaccine Pause Expected To Be Brief, But Subsequent Use May Be Restricted" - Pink Sheet, 13 Apr, 2021.) 

The adverse events are of course different. While Guillain-Barré syndrome is a serious neurological disorder, and the events appear more widespread than the blood clots, there appear to be fewer deaths attributed to GBS associated with the J&J vaccine. 

The blood clot announcement featured a press conference with numerous government officials, and the issue was also discussed during the White House daily briefing. (Also see "White House Reiterates Confidence In FDA Expertise, Independence With J&J Vaccine Pause" - Pink Sheet, 13 Apr, 2021.)

In contrast, news of the Guillain-Barré syndrome reached the public in what seemed like a trial balloon. The Washington Post first reported the adverse event, and CDC and FDA eventually issued statements, but engaged in no active outreach on GBS.

Taking a different approach is understandable after the government’s decision to encourage a pause in J&J vaccinations in response to the blood clots came in for a fair bit of criticism, particularly once it became clear that mid-April was the high-water mark for vaccine administration in the US.

The seven-day rolling average actually peaked on 13 April, the day of the pause announcement, and has fallen steadily since then. After topping out at 3.38 daily million doses administered, it now sits at around 506,000, about the same number of shots that were being administered in January before distribution ramped up, while almost one-third of US adults remain unvaccinated.  

The pause for the J&J vaccine is not the only reason for the slowdown in vaccinations, but it certainly seems to be a factor, and the cantankerous discussion of how the pause should have been lifted may have contributed as well.

After the announcement of the pause, a next-day ACIP was convened, and FDA seemed willing to lift the pause if the committee endorsed the move, but panelists opted not to, declaring they did not yet have any more information than the officials who had recommended the pause. (Also see "Rejecting FDA Advice, ACIP Defers J&J COVID Vaccine Blood Clot Decision Until It Gets More Data" - Pink Sheet, 14 Apr, 2021.)

Ten days later, after more events had been compiled, CDC’s advisory committee voted to lift the pause and a warning and precaution regarding thrombosis with thrombocytopenia (TSS) was added to the vaccine’s label. (Also see "With J&J’s COVID Vaccine Pause Now Lifted, The Question Is How Well The System Worked" - Pink Sheet, 23 Apr, 2021.)

At a subsequent ACIP meeting in May, some panel members pushed for stronger warnings following additional reports of cases of TSS in a wider age range of women. (Also see "J&J Vaccine: Some CDC Advisors Question Warning’s Strength As Clot Reports Grow, Female Use Drops" - Pink Sheet, 14 May, 2021.)

Whether that history drove the government’s handling of the GBS events or officials decided to take a different approach for unrelated reasons remains unclear.

GBS Risk Added To Vaccine Fact Sheets

Unlike the unusual constellation of systems presented with TSS, Guillain-Barré syndrome is a rare but routine condition in which the body’s immune system damages nerve cells, causing muscle weakness, or in the most severe cases paralysis. CDC said an estimated 3,000 to 6,000 people develop GBS in the US each year and most fully recover. It is typically triggered by a respiratory or gastrointestinal infection.

CDC notes on its website that there was a small increased risk of GBS after swine flu vaccination in 1976 and that there have been several studies of the risk of GBS after flu vaccine. It says the data on an association between seasonal influenza vaccine and GBS has been variable from season-to-season and when there has been an increased risk, it has consistently been in the range of 1-2 additional GBS cases per million flu vaccine doses administered.

The FDA is addressing GBS with revisions to the vaccine recipient and vaccine provider fact sheets. The agency said the fact sheet for healthcare providers administering vaccine has been revised to include a warning about GBS and notes that reports of adverse events suggest an increased risk of GBS.

The fact sheet for recipients and caregivers has been revised to include information about GBS and notes that vaccine recipients should seek medical attention right away if they develop any of a list of symptoms after receiving the Janssen vaccine, including weakness or tingling sensations, especially in the legs or arms, that's worsening and spreading to other parts of the body; difficulty walking; difficulty with facial movements, including speaking, chewing or swallowing; double vision or inability to move eyes; or difficulty with bladder control or bowel function.

J&J said in a 12 July statement that it has been in discussions with the FDA and other regulators about rare cases of GBS that have been reported following vaccination with its vaccine.

“The chance of having this occur is very low, and the rate of reported cases exceeds the background rate by a small degree,” the company said. “Any adverse event report about individuals receiving Johnson & Johnson’s single-shot vaccine, as well as our own assessment of the report, is shared with the U.S. Food and Drug Administration, the European Medicines Agency and other appropriate health authorities. We strongly support raising awareness of the signs and symptoms of rare events to ensure they can be quickly identified and effectively treated.”

Four Adverse Events of Interest With Pfizer/BioNTech Vaccine

The risk of blood clots, which have also reported with AstraZeneca PLC’s COVID-19 vaccine in the countries where it has been cleared, and GBS have not been observed with Pfizer Inc./BioNTech SE and Moderna, Inc.’s mRNA vaccines.

However, there have been reports of myocarditis/pericarditis following administration of the mRNA vaccines, particularly in older male adolescents and young men. FDA said it would add warning language about the risk to the fact sheets for the vaccines and ACIP concluded that the benefit-risk of the two vaccines remains favorable. (Also see "mRNA COVID-19 Vaccines To Add Warning Language On Myocarditis Risk" - Pink Sheet, 23 Jun, 2021.)

The list of adverse events for Pfizer/BioNTech’s vaccine also continues to expand as its use does. On 9 July, the FDA posted a statement about initial results of near real-time safety monitoring of COVID-19 vaccines in persons aged 65 years and older. The agency said the surveillance detected four potential adverse events of interest (AEI) in the Medicare healthcare claims database of persons in this age group who had received Pfizer/BioNTech’s vaccine: pulmonary embolism, acute myocardial infarction, immune thrombocytopenia, and disseminated intravascular coagulation.

The agency said the screening methods have not identified these AEI in persons 65 years and older who received the two other authorized COVID-19 vaccines, Moderna’s and J&J’s.

“These four events may not be true safety concerns, and the screening method cannot establish that the vaccine caused these AEI. FDA is sharing the initial findings of this safety study in the spirit of transparency but does not believe there is a cause for concern,” the agency stated. “There are alternative explanations for the findings, including the fact that the Pfizer/BioNTech vaccine was given to many high-risk individuals who were older and had significant co-morbidities.”