No significant increase in Guillain-Barré syndrome after COVID-19 vaccination in adults: A vaccine adverse event reporting system study.

OBJECTIVE: To investigate the association between Guillain-Barré syndrome (GBS) and COVID-19 vaccination. BACKGROUND: On July 13, 2021, the US Food and Drug Administration (FDA) released a new warning that Johnson & Johnson COVID-19 vaccine could increase the risk of developing GBS. METHODS: The reporting rate of adult GBS after COVID-19 vaccination, ascertained with Brighton criteria, was compared with the reporting rate after other vaccinations during the same time period, and also compared with the reporting rate during control periods. Statistical methods such as proportion tests, and Pearson's chi-squared test were utilized to identify significant relationships. Self-controlled and case centered analyses were conducted. A machine learning model was utilized to identify the factors associated with a worse outcome defined as emergency room (ER) or doctor visits, hospitalizations, and deaths. RESULTS: The reporting rate of GBS after COVID-19 vaccination was significantly higher than after influenza and other vaccinations (49.7, 0.19, 0.16 per 10 million, p < 0.0001). However, the reporting rate was within the incidence range of GBS in the general population. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of GBS after COVID-19 vaccination between the risk period and control period (p < 0.0001). There was an estimated 0.7-1.7 per million excess reports of GBS within 6 weeks of COVID-19 vaccination. Machine learning model demonstrated that female gender and age between 18 and 44 are associated with worse outcome. No association was found between the onset interval of GBS and its prognosis. CONCLUSIONS: Although the reporting rate of GBS after COVID-19 vaccination was not statistically different than that of the general population, the increased reporting of GBS within the first 6 weeks after COVID-19 vaccination, more so than with other vaccinations, suggests that some cases of GBS are temporally associated with COVID-19 vaccination. However, there is a reduction in the reporting rate of GBS after other vaccines, compared to reporting rates pre-COVID-19, highlighting limitations inherent in any passive surveillance system. These findings warrant continuous analysis of GBS after COVID-19 vaccination. Further improvement of the machine learning model is needed for clinical use.

Association Between COVID-19 Vaccination and Rhabdomyolysis in Adults: A Vaccine Adverse Event Reporting System (VAERS) Study

Objective: To investigate whether there is an association between rhabdomyolysis and COVID-19 vaccination. Background: Rhabdomyolysis was reported after COVID-19 infection. Design/Methods: The reporting rate of rhabdomyolysis after COVID-19 vaccination was compared to the reporting rate of rhabdomyolysis after all other vaccinations in 3 periods: the vaccine period (December 2020-July 2021);the pre-vaccine period (April 2020-November 2020) and the pre-COVID-19 period (January 2019-August 2019). Self-controlled case series analysis and case-centered analysis was used. Six weeks after vaccination was defined as the risk period of probable cause-effect relationship between vaccination and rhabdomyolysis. Results: 169 and 8 cases of rhabdomyolysis after COVID-19 vaccination and all other vaccinations respectively. During COVID-19 vaccine period, the reporting rate of rhabdomyolysis after COVID-19 vaccination was significantly higher compared to the reporting rate of rhabdomyolysis after all other vaccinations (8.75 vs 0.34 per 10 million p<0.0001). However, it is within the incidence range reported in the general population. Only 4 and 8 cases of rhabdomyolysis after vaccination were reported during pre-vaccine and pre-COVID-19 period respectively. Using self-controlled and case centered analyses, there is a significant difference in the reporting rate of rhabdomyolysis after COVID-19 vaccination between the risk period and control period (98.22% vs 0.06% p<0.0001). The reporting rate of rhabdomyolysis after Johnson and Johnson was not significantly different from the reporting rate after Moderna and Pfizer vaccinations. Conclusions: There is no significant increase in cases of rhabdomyolysis with COVID-19 vaccinations. However, the unbalanced distribution of rhabdomyolysis within the first 12 weeks, with a significant increase in reporting rate, suggests that some rhabdomyolysis cases are temporally associated with COVID-19 vaccination. This supports an autoimmune-mediated muscle injury mechanism rather than direct viral muscle invasion for cases of rhabdomyolysis occurring after COVID-19 infections. Due to limitations in passive surveillance, nonreported or undiagnosed concomitant COVID-19 infections cannot be excluded. Controlled studies are needed for further investigation.

Is COVID-19 Vaccination Associated with an Increased Reporting Rate of MyastheniaGravis? A Vaccine Adverse Event Reporting System (VAERS) Study

Objective: To investigate whether there is an association between Myasthenia Gravis (MG) and COVID-19 vaccination. Background: New onset or exacerbation of MG after vaccination was previously reported. Design/Methods: The reporting rate of MG cases after COVID-19 vaccination was compared to that of MG after all other vaccinations in 3 time periods: the vaccine period (December 2020- July 2021);the pre-vaccine pandemic period (April 2020-November 2020) and pre-pandemic period (January 2019-August 2019). Self-controlled case series analysis and case-centered analysis were used. Six weeks after vaccination was defined as the risk period for possible causeeffect relationship. For self-controlled case analysis, the risk period was followed by one month of washout and another six weeks of control monitoring. Results: 77 and 3 cases with MG after COVID-19 vaccination and all other vaccinations were reported during the vaccine period respectively. The reporting rate of MG after COVID-19 vaccination was significantly higher than the reporting rate of MG after other vaccines (4 vs 0.1 per 10 million p< 0.00001). However, the reporting rate was within the incidence range expected in the general population. Two cases of MG after vaccination were reported during pandemic period and none in the pre-pandemic period. Using self-controlled and case centered analyses, there is a significant difference in the reporting rate of MG after COVID-19 vaccination between the risk period and control period (92.2% vs 2.6-3.9% p<0.00001). The reporting rate of MG after COVID-19 vaccination was not significantly different between Johnson and Johnson, Moderna and Pfizer vaccines. Conclusions: There is no significant increase in reporting rate of MG after COVID-19 vaccination. Although the reporting rate of MG after COVID-19 vaccination was significantly higher during the risk period compared to the control period, a non-reported or undiagnosed concomitant COVID-19 infection, other triggering factors or non-adherence to medications cannot be excluded;this could account for the observed increase.

Investigating the relationship of Miller Fisher Syndrome and COVID-19 Vaccination: A Vaccine Adverse Event Reporting (VAERS) Study

Objective: To investigate whether there is an relationship between Miller Fisher Syndrome (MFS) and COVID-19 vaccination Background: MFS was rarely reported after COVID-19 vaccination. Design/Methods: The reporting rate of MFS cases after COVID-19 vaccination was compared to the rate after all other vaccinations in 3 time periods: COVID-19 vaccination (December 2020 - July 2021);COVID-19 pandemic outside the vaccination time period (April 2020-November 2020) and the time outside of COVID-19 vaccination and the pandemic (January 2019-August 2019). Self-controlled case series analysis and case-centered analysis was used. Six weeks after vaccination was defined as the risk period of possible association. Results: 12 cases after COVID-19 vaccination and 1 case from all other vaccinations were reported during the vaccine period. The reporting rate of MFS after COVID-19 vaccination (0.62 per 10 million vaccinations) was significantly higher than the rate after other vaccinations (0.04 per 10 million vaccinations) p<0.05. Both reporting rates are within the incidence range expected in the general population. No cases of MFS were reported during the pandemic period and 2 cases of MFS were reported outside the pandemic period. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of MFS after COVID-19 vaccination between the risk period and control period (91.6% vs 0-8,3% p<0.00001). The reporting rate of MFS after each vaccine used in USA (Johnson & Johnson, Pfizer and Moderna) was within the expected incidence range and there was no significant difference between them. Conclusions: There is no association between MFS and COVID-19 vaccination. Although the reporting rate MFS after COVID-19 was significantly higher during the risk period compared to control period, and compared to the rate of other vaccines, the number of reported cases was low and within the expected incidence range. Furthermore, cases of MFS related to COVID-19 infection or other triggering factors cannot be excluded.

Association Between COVID-19 Vaccination and Optic Neuritisin Adults: A Vaccine Adverse Event Reporting System (VAERS) Study

Objective: To investigate whether there is an association between Optic Neuritis and COVID-19 vaccination. Background: Optic Neuritis has been reported after COVID-19 infections. Design/Methods: The reporting rate of Optic Neuritis cases after COVID-19 vaccination was compared to the reporting rate of Optic Neuritis after Influenza vaccination and after other vaccination in 3 time periods: the COVID-19 vaccine period (December 2020-July 2021);the pre-COVID-19 vaccine period (April 2020-November 2020) and the pre-COVID-19 period (January 2019-August 2019). Self-controlled case series and case-centered analyses were used. Six weeks after vaccination was defined as the risk period of probable association. Results: 89 cases with Optic Neuritis after COVID-19 vaccination and 3 cases after all other vaccinations were reported during COVID-19 vaccination period. The reporting rate of Optic Neuritis cases after COVID-19 vaccination is significantly higher compared to Optic Neuritis after other vaccinations (0.46 vs 0.012 per million vaccination p<0.0001). However, this is within the incidence range reported in the general population. Only 3 and 2 cases of Optic Neuritis were reported after vaccination during and outside the pandemic time period respectively. Using self-controlled and case centered analyses, there is a significant difference in the reporting rate of Optic Neuritis after COVID-19 vaccination between the risk and control period (97.8% vs 0-2.2% p<0.0001). The reporting rate of Optic Neuritis after each vaccine used in USA (Johnson & Johnson, Pfizer and Moderna) is within the expected incidence range and there was no significant difference between them. Conclusions: There is no association between Optic Neuritis and COVID-19 vaccination. Although the reporting rate of Optic Neuritis after COVID-19 is significantly higher during the risk period compared to control period and compared to the reporting rate after other vaccines, it is within the expected incidence range. In addition, cases of Optic Neuritis triggered by unreported or undiagnosed demyelination, autoimmunity, infection and neuroinflammation cannot be excluded.

Investigating Cerebral Sinus Venous Thrombosis after COVID-19 Vaccination in Adults

Objective: To investigate whether there is an association between Cerebral Sinus Venous Thrombosis (CSVT) and COVID-19 vaccination. Background: CSVT has been reported after COVID-19 infections. Design/Methods: Data from the Vaccine Adverse Event Reporting System (VAERS) was used. The reporting rate of CSVT cases after COVID-19 vaccination was compared to the reporting rate of CSVT after all other vaccinations in 3 time periods: the vaccine period (December 2020- July 2021), the pre-vaccine period (April 2020-November 2020) and the pre-COVID-19 period (January 2019-August 2019). Self-controlled case series and case-centered analysis were used. Six weeks after vaccination was defined as the risk period of probable association. Results: 217 cases with CSVT after COVID-19 vaccination were reported during COVID-19 vaccination period. The reporting rate of CSVT after COVID-19 vaccination was 1.12 per million vaccination, which is in the range of incidence within the general population. No cases of CSVT were reported after all other vaccinations in the vaccine period, pre-vaccine period and pre-COVID-19 period. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of CSVT after COVID vaccination between the risk and control period (88.9% vs 1.8-6.0% p<0.0001). The reporting rate of CSVT for each vaccine used in USA was significantly higher with Johnson & Johnson compared to Pfizer and Moderna vaccines (2.75 vs 1.3 vs 0.8 <0.0001). All reporting rates did not exceed the incidence of CSVT in the general population. Conclusions: There is no association between CSVT and COVID-19 vaccination. Although the reporting rate of CSVT after COVID-19 was significantly higher during the risk period compared to control period, it was within the expected incidence range in general population. In addition, cases of CSVT triggered by unreported or undiagnosed infection and inflammation cannot be excluded. Controlled studies are needed to assess the relationship between CSVT and COVID-19 vaccination.

Reporting Rates of Encephalopathy Post-COVID-19 Vaccination: A Vaccine Adverse Event Reporting System (VAERS)

Objective: To investigate whether there is an association between Encephalopathy and COVID-19 vaccination. Background: Encephalopathy has been reported in COVID-19 vaccinations. Design/Methods: The reporting rate of Encephalopathy cases after COVID-19 vaccination was compared to the reporting rate of Encephalopathy after all other vaccinations in 3 periods: COVID-19 vaccination (December 2020 - July 2021);COVID-19 pandemic outside the vaccination period (April 2020 - November 2020) and time outside both the COVID-19 vaccination and the pandemic (January 2019 - August 2019). Self-controlled case series analysis and case-centered analysis was used. Six weeks after vaccination was defined as the risk period of probable association between Encephalopathy and COVID-19 vaccination. Results: 371 and 4 cases of Encephalopathy were reported after COVID-19 vaccination and all other vaccinations respectively during the COVID-19 vaccination period. The reporting rate of Encephalopathy after COVID-19 vaccination was significantly higher than the reporting rate of Encephalopathy after all other vaccinations (1.9 vs 0.017 per million p<0.00001). However, the reporting rate of Encephalopathy after COVID-19 vaccination was within the incidence range expected in the general population. 12 and 23 cases of Encephalopathy were reported after vaccination during the pandemic period and outside the pandemic period. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of Encephalopathy after COVID-19 vaccination between the risk and control periods (94.33% vs 1.08-2.70% p< 0.0001). The reporting rate of Encephalopathy after Pfizer was significantly higher compared to that of Encephalopathy after Moderna and Johnson & Johnson vaccinations. However, all reporting rates were within the incidence range reported in the general population. Conclusions: There is no association between Encephalopathy and COVID-19 vaccination. Furthermore, this work is based on passive surveillance where several limitations exist, which include under reporting, differential reporting and nonreported or undiagnosed concomitant COVID-19 infection. These factors preclude establishing a cause-effect relationship. Controlled studies are needed for further investigation.