Virus World

Two people who received Pfizer's respiratory syncytial virus (RSV) vaccine during a clinical trial were later diagnosed with Guillain-Barre syndrome, and the US Food and Drug Administration has asked Pfizer to conduct a safety study if the shot is approved, according to agency documents released Friday. The cases were confirmed in two adults in their 60s who were among 20,000 vaccine recipients in Pfizer’s Phase 3 clinical trial. One person’s illness had completely resolved after three months, and another was improving after six months. There were no Guillain-Barre cases among people who didn’t receive the shot. “Given the temporal association and biological plausibility, FDA agrees with the assessments of the investigators that these events were possibly related to study vaccine. … Therefore, [Guillain-Barre] is being considered an important potential risk,” the FDA says in the documents, which were released ahead of a meeting of its independent vaccine advisers, the Vaccines and Related Biological Products Advisory Committee, on Tuesday and Wednesday.

The committee is scheduled to discuss and make recommendations on RSV vaccines for adults 60 and older from Pfizer and GSK. Guillain-Barre syndrome is a rare neurological disorder in which the immune system attacks its own nerves, causing muscle weakness and sometimes paralysis. Although most people recover completely, some cases can be fatal or have lasting effects. The incidence of Guillain-Barre is about 1.5 to 3 cases for 100,000 adults over age 60 in the US annually, according to the FDA.

“Given the higher than background rate of GBS observed in the Phase 3 study, FDA will recommend a postmarketing study and enhanced surveillance for further evaluation of GBS and other immune-mediated demyelinating conditions with postmarketing use,” the FDA says. In a briefing document submitted for next week’s meetings, Pfizer says that the cases have other possible explanations and that its shot is a “well-tolerated and safe vaccine, with a benefit-to-risk ratio that is favorable.” The company says it will conduct a safety study on Guillain-Barre syndrome if its RSV shot is approved. RSV is a highly contagious virus that causes flu-like illness in people of all ages that increases in severity with age. According to the US Centers for Disease Control and Prevention, RSV is responsible for an estimated 177,000 hospitalizations and 14,000 deaths per year among adults 65 or older. There are no vaccines approved for immunization against RSV in either children or with adults. The Pfizer vaccine was 66.7% effective at preventing moderated lower respiratory tract illness with two or more symptoms and 85.7% effective at preventing severe illness, the FDA documents say. GSK’s RSV vaccine candidate for older adults was 83.5% effective at preventing severe lower respiratory tract disease. The company similarly reported a potential case of Guillain-Barre syndrome among vaccine recipients but said there was insufficient evidence to confirm a diagnosis. The FDA considers the case to be related to the vaccine and said it will review GSK’s safety plan. Data from both vaccines was discussed Thursday during a meeting of the CDC’s Advisory Committee on Immunization Practices. The working group concluded that the vaccines “demonstrated significant efficacy against lower respiratory tract illness caused by RSV among older adults” but that “post licensure surveillance for both safety and vaccine effectiveness will be critical” if the vaccines are approved by the FDA.

The "mRNA COVID-19 vaccines may be administered to people with underlying medical conditions provided they have not had a severe allergic reaction to any of the ingredients in the vaccine," the CDC wrote in updated guidance. The Centers for Disease Control and Prevention (CDC) issued new COVID-19 vaccine guidance, which indicates that those with preexisting medical conditions should receive the vaccine. "Adults of any age with certain underlying medical conditions are at increased risk for severe illness from the virus that causes COVID-19," the CDC wrote in updated guidance on December 26, adding that "mRNA COVID-19 vaccines may be administered to people with underlying medical conditions provided they have not had a severe allergic reaction to any of the ingredients in the vaccine." The two different vaccines that are currently being administered to Americans use mRNA technology, which tells the body to create antibodies to combat the virus, instead of using a weakened version of the virus. The two vaccines include one developed by Pfizer and German biotech company, BioNTech and the other developed by Moderna.  The CDC's COVID-19 vaccine update provides guidance for those with several different preexisting medical conditions including weakened immune systems, autoimmune conditions, Guillain-Barre syndrome and Bell's palsy.

As the CDC notes, people with HIV and weakened immune systems "due to other illnesses or medication might be at increased risk for severe COVID-19." The CDC states that these people should receive a COVID-19 vaccine but notes that "information about the safety of mRNA COVID-19 vaccines" for this group is not yet available. "People living with HIV were included in clinical trials, though safety data specific to this group are not yet available at this time," the CDC said.  The CDC provides similar guidance for those with autoimmune conditions, stating that this group should receive a COVID-19 vaccine but adds that "they should be aware that no data are currently available on the safety of mRNA COVID-19 vaccines for them." According to the CDC, to date, there have been no reported cases of Guillain-Barre syndrome after a person received a COVID-19 vaccine during clinical trials and people who previously had GBS should receive the vaccine. On December 17, the Food and Drug Administration reported cases of Bell's palsy in people who received the Pfizer and Moderna vaccines during clinical trials. Bell's palsy is a temporary facial paralysis, but in the CDC's updated guidance, it states that the FDA "does not consider these [cases] to be above the rate expected in the general population." "They have not concluded these cases were caused by vaccination. Therefore, persons who have previously had Bell's palsy may receive an mRNA COVID-19 vaccine," the CDC stated.

The CDC's updated guidance also states that even after receiving a COVID-19 vaccine, people should continue to follow the current guidance to combat the virus. The current guidelines include wearing a protective face mask while in public, following social distancing measures, washing hands, and following quarantine guidance after being exposed to the virus.  The updated guidance comes as the CDC and many other health authorities have said that those with preexisting medical conditions are at a heightened risk of developing serious cases of the novel virus. Newsweek reached out to the CDC for comment but did not receive a response in time for publication. The updated guidance comes as the CDC and many other health authorities have said that those with preexisting medical conditions are at a heightened risk of developing serious cases of the novel virus. Newsweek reached out to the CDC for comment but did not receive a response in time for publication.

Updated CDC guidelines (Dec. 29, 2020):

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/underlying-conditions.html

Question  Are Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccines associated with Guillain-Barré syndrome (GBS) within 21 or 42 days after vaccination?

Findings  This cohort study of 487 651 785 COVID-19 vaccine doses found that in observed-to-expected analyses, the observed number of GBS reports was higher than expected based on background rates within 21 and 42 days after vaccination for Ad26.COV2.S but not BNT162b2 or mRNA-1273. GBS reporting rates within 21 and 42 days of Ad26.COV2.S vaccination were 9 to 12 times higher than after BNT162b2 or mRNA-1273 vaccination.

Meaning  These findings suggest that Ad26.COV2.S vaccination was associated with GBS and that GBS after BNT162b2 and mRNA-1273 may represent background incidence.

Importance  Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring.

Objective  To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines.

Design, Setting, and Participants  This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included.

Exposures  Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine.

Main Outcomes and Measures  Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates.

Results  Among 487 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods.

Conclusions and Relevance  This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.

As if the symptoms of COVID-19 were not disturbing enough, physicians have noted a rare neurological condition that emerges during some severe cases of this viral infection. The patient in the case report (let’s call him Tom) was 54 and in good health. For two days in May, he felt unwell and was too weak to get out of bed. When his family finally brought him to the hospital, doctors found that he had a fever and signs of a severe infection, or sepsis. He tested positive for SARS-CoV-2, the virus that causes COVID-19 infection. In addition to symptoms of COVID-19, he was also too weak to move his legs. When a neurologist examined him, Tom was diagnosed with Guillain-Barre Syndrome, an autoimmune disease that causes abnormal sensation and weakness due to delays in sending signals through the nerves. Usually reversible, in severe cases it can cause prolonged paralysis involving breathing muscles, require ventilator support and sometimes leave permanent neurological deficits. Early recognition by expert neurologists is key to proper treatment.

We are neurologists specializing in intensive care and leading studies related to neurological complications from COVID-19. Given the occurrence of Guillain-Barre Syndrome in prior pandemics with other corona viruses like SARS and MERS, we are investigating a possible link between Guillain-Barre Syndrome and COVID-19 and tracking published reports to see if there is any link between Guillain-Barre Syndrome and COVID-19.

Some patients may not seek timely medical care for neurological symptoms like prolonged headache, vision loss and new muscle weakness due to fear of getting exposed to virus in the emergency setting. People need to know that medical facilities have taken full precautions to protect patients. Seeking timely medical evaluation for neurological symptoms can help treat many of these diseases.

Guillain-Barre syndrome occurs when the body’s own immune system attacks and injures the nerves outside of the spinal cord or brain – the peripheral nervous system. Most commonly, the injury involves the protective sheath, or myelin, that wraps nerves and is essential to nerve function. Without the myelin sheath, signals that go through a nerve are slowed or lost, which causes the nerve to malfunction...