2 Update COVID-19 list of Adverse events (SO2-D2.1.2.)

As part of its work to harmonize safety assessment of CEPI-funded vaccines, the Safety Platform for Emergency vACcines (SPEAC) Project has generated a list of adverse events of special interest (AESI) for safety monitoring based on one or more of the following criteria: 1) known association with immunization or a specific vaccine platform; 2) theoretical association based on animal models; 3) occurrence during wild-type disease as a result of viral replication and/or immunopathogenesis. COVID-19 is unique as an emerging pandemic pathogen with an ever-expanding variety of clinical manifestations which might occur as presenting complaints and/or emerge during and following the course of acute disease. The first SPEAC COVID-19 AESI list was created in March 2020 based on the experience in China; it was updated in May 2020 as the global experience with the SARS-CoV-2 viral infection expanded. The May 2020 list was adopted by the WHO Global Advisory Committee on Vaccine Safety (GACVS) at their May 27-28, 2020 meeting. Subsequently, SPEAC implemented a systematic review process to ensure an ongoing understanding of the full spectrum of COVID-19 disease and modification of the AESI list accordingly. The first evidence-based update was completed in September 2020 with no AESIs added to the May 2020 list. This document provides detailed methods and results of the December 2020 COVID-19 quarterly update. Separate annexes are included consolidating all reviews since March 2020, summarizing publication type and frequency of events, by body system. A companion excel spreadsheet has been prepared which contains the full citations with download links included in the March, May, September and December 2020 updates separated into tabs by body system. Four secondary objectives are also addressed: 1) a reassessment of the need for Brighton case definitions to be created for all the AESIs on the May 2020 list, 2) consideration of new AESIs for addition to the list, 3) consolidation of the systematic reviews presented in May, September and December 2020 and 4) consideration of the need for a change in focus of the next update due in March 2021. Based on the findings presented in the December 2020 update SPEAC recommends the following: 1. Three new events are added to the COVID-19 AESI list: rhabdomyolysis, subacute thyroiditis and acute pancreatitis. 2. For the prior listed AESI acute kidney injury recommend use of the international criteria defined by the Kidney Disease Improving Global Outcomes (KDIGO) expert consensus group in 2012 rather than develop a new Brighton case definition. 3. For the prior listed AESI acute liver injury, adopt what has been used in many COVID-19 publications reporting elevations above the upper normal limit of >3-fold for AST/ALT and >2-fold for total bilirubin, GGT and ALP rather than develop a Brighton case definition. 4. Pending publication of the Brighton case definition on cardiovascular injury which will focus on myocarditis and pericarditis, and in-depth review of existing meta-analyses and systematic reviews, defer a decision regarding development of additional Brighton case definitions for the other entities included in cardiovascular injury (arrhythmia, acute coronary syndrome, heart failure, cardiogenic shock, stress cardiomyopathy and microangiopathy). 5. For the next COVID-19 update, due in March 2021, limit the focus to COVID-19 disease outcomes in pregnancy and childhood along with long term complications.The SPEAC Project is funded in whole by CEPI