key: cord-0824067-rqs4d9sc authors: Spadaccini, Marco; Canziani, Lorenzo; Aghemo, Alessio; Lleo, Ana; Maselli, Roberta; Anderloni, Andrea; Carrara, Silvia; Fugazza, Alessandro; Pellegatta, Gaia; Galtieri, Piera Alessia; Hassan, Cesare; Greenwald, David; Pochapin, Mark; Wallace, Michael; Sharma, Prateek; Roesch, Thomas; Bhandari, Pradeep; Emura, Fabian; Raju, Gottumukkala S; Repici, Alessandro title: What gastroenterologists should know about SARS–CoV 2 vaccine: World Endoscopy Organization perspective date: 2021-06-08 journal: United European Gastroenterol J DOI: 10.1002/ueg2.12103 sha: f19a5c41b5d4be02d7bf678f55a439825030cb17 doc_id: 824067 cord_uid: rqs4d9sc BACKGROUND: The novel Coronavirus (SARS‐CoV‐2) has caused almost 2 million deaths worldwide. Both Food and Drug Administration and European Medicines Agency have recently approved the first COVID‐19 vaccines, and a few more are going to be approved soon. METHODS: Several different approaches have been used to stimulate the immune system in mounting a humoral response. As more traditional approaches are under investigation (inactivated virus vaccines, protein subunit vaccines, recombinant virus vaccines), more recent and innovative strategies have been tried (non‐replicating viral vector vaccines, RNA based vaccines, DNA based vaccines). RESULTS: Since vaccinations campaigns started in December 2020 in both the US and Europe, gastroenterologists will be one of the main sources of information regarding SARS‐CoV 2 vaccination for patients in their practice, including vulnerable patients such as those with Inflammatory Bowel Disease (IBD), patients with chronic liver disease, and GI cancer patients. CONCLUSIONS: Thus, we must ourselves be well educated and updated in order to provide unambiguous counseling to these categories of vulnerable patients. In this commentary, we aim to provide a comprehensive review of both approved COVID‐19 vaccines and the ones still under development, and explore potential risks, benefits and prioritization of vaccination. Since December 2019, when the World Health Organization (WHO) was informed of the first cases of pneumonia of unknown etiology, 1 the novel Coronavirus (SARS-CoV-2) has caused more than 94 ,000,000 cases and almost 2 million deaths worldwide, as of 16th January. 2 The world community has responded to the deadly challenge of Coronavirus-related disease (COVID-19) by relying on several public containment measures in order to slow down the spread of the virus. 3, 4 As of today, no drug has been proved to be a game-changer in the fight against the COVID-19, 5,6 and our hope for an end to this pandemic led to an unprecedented fast track path for developing a reliable vaccine. (Table 1) Though primarily considered as a respiratory disease, gastroenterologists had to face the SARS-CoV 2 pandemic in different ways in their everyday practice. First, COVID-19 may affect various systems including the digestive tract, causing gastrointestinal (GI) symptoms such as diarrhea, nausea, and abdominal pain in around 12% of patients. 7 Furthermore, the risk of exposure of health care workers has been relevant in endoscopy units, considering that COVID-19 is spread via an airborne route. Indeed, endoscopy demands short physical distance from patients to personnel and endoscopists are exposed to various biological material. [8] [9] [10] This risk could be even more relevant considering the detection of SARS-CoV 2 in biopsy specimens and stool, suggesting a possible faecal-oral transmission. 7 However, adequate use of personal protective equipment and other infection control measures 11 seemed to lead to a low risk of COVID-19 transmission in GI endoscopy units. [12] [13] [14] After Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval, vaccinations campaigns started in December 2020 in both the US and Europe. Gastroenterologists will be one of the main sources of information regarding SARS-CoV 2 vaccination for patients in their practice, including vulnerable patients such as those with Inflammatory Bowel Disease (IBD), 15 patients with chronic liver disease, and GI cancer patients. 16 Thus, we must ourselves be well educated and updated in order to provide unambiguous counseling to these categories of vulnerable patients. In this commentary, we provide a comprehensive review of both approved COVID-19 vaccines and the ones still under development, and explore potential risks, benefits and prioritization of vaccination in order to properly guide patients' awareness and choices. Coronaviruses are single-stranded, positive-sense RNA enveloped viruses. 17, 18 Two Alphacoronaviruses (229E and NL63) and two Betacoronaviruses lineage A (OC43 and HKU1) are known to elicit common cold symptoms and are endemic. 19 All trials compared the safety and efficacy of the vaccine against normal saline, except for ChAdOx1 nCoV-19 that was compared to Meningococcal group A, C, W, and Y conjugate vaccine or normal saline. All vaccines are administered intramuscularly. SPADACCINI ET AL. A cause of concern is the evidence for some betacoronaviruses of antibody-dependent enhancement (ADE) of the virus. 26 Instead of neutralizing the virions, antibodies may promote viral invasion in some types of cell. In particular, SARS-CoV viruses enter macrophages through the antibody Fc portion and skew macrophage function. 27 In MERS-CoV, the interaction of a monoclonal antibody induces conformational changes and causes viral entry through the Fc portion. 26 This phenomenon is partly dependent on the concentration of the antibody, so a high titer of neutralizing antibodies may prevent ADE of the virus. 26 Further, the introduction of an adjuvant may promote Th2-type immunity and reduce the immunopathology. 28 There is no clear evidence of ADE of the virus in SARS-CoV-2, but it may explain conflicting results in the use of convalescent plasma. 29 Also, it mandates to evaluate candidate vaccines for prevention of either mild or severe COVID-19. To date, no approved vaccine for SARS-CoV-2 demonstrated ADE of the virus. [30] [31] [32] In phase 1/2 trials, efficacy was measured as immunogenicity 33, 34 defined as antibody titer against the defined antigen. In phase 3 trials, the efficacy was defined as difference in number of symptomatic infections. 30, 31 Up to date, no test is recommended to assess vaccine efficacy after the scheduled doses; it seems reasonable, though, to measure antibody titer in selected patients. Also, as no trial published results for asymptomatic carriage, it is not yet known if vaccinated people may still carry and transmit the virus (i.e., "sterilizing immunity"). 35 Therefore, prevention strategies should be maintained in the vaccinated population. Up to January 16, 2021, 237 vaccine candidates for COVID-19 had been reported, and 64 of them were in human clinical trials. 36 Three of them have completed phase 3 trials, and reports are pub- Host cell machinery produces antigens using genetic material delivered vaccines (3) (4) (5) Liver diseases of viral etiology are not per se associated with COVID-19 disease severity or outcome and the same holds true for liver transplanted patients [89] [90] [91] [92] vaccines would not be safe and effective in protecting these patients. Thus, these categories, including liver transplant recipients, 98 should be strongly encouraged to get vaccinated against COVID-19 with any of the approved vaccines when one is offered to them, as recently recommended by national and international societies 99, 100 Finally, we would like to emphasize that other recommended vaccinations for patients with chronic diseases and/or immunosuppression (i.e., influenza, pneumococcal vaccines) should be administered during this pandemic just as they would have in pre-COVID era. As the current critical pressures squeeze health-care systems world- Finally, we should consider that HCW attitude and utilization of vaccines is a positive example for others and an accepted factor for reducing patient's hesitation and improving adherence to vaccination schedules. 111 This review is based on the available evidence at the time of its preparation and may not apply in all situations. 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