Federal Office of Public Health FOPH Implied fragment EKIF Federal Commission for Federal Department of Home Affairs FDHA Stand 03.04.2023 Federal Office of Public Health (BAG) and Federal Commission for Vaccination (EKIF) Vaccination recommendation for the Covid-19 vaccination (valid from April 3rd, 2023) This document describes the recommendation for a Covid-19 vaccination for the period Spring/ Summer 2023: In individual cases, people who are particularly at risk can be vaccinated against Covid-19 at the discretion of the doctor treating them. In principle, the FOPH and EKIF will not formulate a recommendation for vaccination against Covid-19 in spring/ summer 2023 due to the expected low virus circulation and the high level of immunity in the population . Only in the event of an emerging SARS- CoV-2 wave would people at high risk (BGP) whose last vaccination dose was more than 6 months ago be recommended to be vaccinated against Covid-19. In this case, the recommendation would be updated accordingly by BAG and EKIF. Machine Translated by Google Implied fragment EKIF Federal Office of Public Health FOPH Federal Department of Home Affairs FDHA Federal Commission for Table of contents 4 Recommended vaccine and interval for vaccination 3 11 5.1.4.2 Booster vaccination credentials 4 5 5 Adjustments since last update 3.4.1 Bivalent mRNA vaccines 3.4.2 Protein vaccine Nuvaxovid® 6 7 8 9 11 5.1.1 Definition of severe immunodeficiency 5.1.2 Vaccination response to Covid-19 mRNA vaccines in severe immunodeficiency 15 16 20 3.4.3 Monovalent mRNA vaccines 1 Introduction 3 Covid-19 vaccination in spring/ summer 2023 12 13 13 passive immunization for severely immunodeficient individuals Immunity situation of the Swiss population Target group: Vulnerable people (BGP) 5.2.1 Vaccination schedule and timing after stem cell transplantation 5 Procedure for special groups of people 11 4 6 5.1.3 Vaccination timing for severe immunodeficiency 5.1.4 Vaccination schedule for individuals with severe immunodeficiency 13 16 17 12 5.1.5 Vaccination antibody determination in people with severe immunodeficiency 5.1.6 Use of monoclonal antibody therapies for SARS- CoV-2 infection and Attachments 4 9 10 10 2 Initial situation Overarching goals of the Covid-19 vaccination immunosuppressive treatments Rationale for a Covid-19 vaccination in spring/ summer 2023 4 Adverse Vaccination Symptoms (UIE) 15 People after stem cell transplantation 17 Vaccination effectiveness, reinfection risk, disease severity vaccination recommendation Individuals with severe immunodeficiency 5.1.4.1 Primary immunization (3 doses) pregnancy and breast feeding period 2 Machine Translated by Google Federal Office of Public Health FOPH Implied fragment EKIF Appendix 1: Tabular overview of vaccination recommendations Federal Department of Home Affairs FDHA Federal Commission for Appendix 2: Implementation of the vaccination Attachments Appendix 3: Properties of the vaccines Diseases (procedure in case of allergy history) Annex 6: Recommendations for the Covid-19 vaccination of patients with allergic Appendix 5: Adverse vaccination symptoms (UIE) after Covid-19 vaccination Appendices drawn up, to which reference is made at the appropriate place in the text: 3 Appendix 4: Efficacy of the vaccines In addition to the present vaccination recommendation, the BAG and EKIF have the following further information Appendix 7: Vaccination with the vector vaccine COVID-19 Vaccine Janssen® from Johnson&Johnson Machine Translated by Google • In principle, the FOPH and EKIF will not formulate a recommendation for vaccination against Covid-19 in spring/ summer 2023 due to the expected low virus circulation and the high level of immunity in the population. 4 The vaccination recommendation has been fundamentally revised. The most important changes to the content are: 3. Reduction of the negative direct and indirect health, psychological, social and economic effects during a Covid 19 pandemic This document focuses on the epidemiology of and vaccination against Covid-19 in spring and summer 2023 and replaces the previous document "Vaccination recommendation for Covid-19 vaccination in autumn/ winter 2022/23, as of November 29th, 2022". A tabular overview of the applicable recommendations is published separately in Appendix 1. The goals are to be seen in hierarchical descending order or in the sense of an escalation if the epidemiological situation should require this. Due to the immunity situation in the population (see Chapter 2.2), the currently predominant virus variants and the expected low virus circulation for spring/ summer 2023, goals 1 and 2 are in the foreground. In particular, the BGP are to be protected, as they are due to their age, an underlying disease or other circumstances 2. Ensuring health care The vaccination recommendation is based on the Covid-19 vaccination strategy of the BAG and EKIF. It is constantly updated to reflect current scientific knowledge and data. The present document deals with the recommendations for Covid-19 vaccination in spring/ summer 2023 and includes all vaccines against Covid-19 approved in Switzerland. Certain contents are published as separate attachments, to which reference is made at the appropriate place. diseases • Vaccination against Covid-19 would only be recommended for people at high risk (BGP) whose last vaccination dose was more than 6 months ago in the event of an emerging SARS- CoV-2 wave (see Chapter 3.3). In this case, the recommendation would be updated accordingly by BAG and EKIF. 1. Reducing the burden of disease, especially of severe and fatal Covid-19 BAG and EKIF are still: • Vaccination against Covid-19 means a single vaccine dose, regardless of the number of doses of vaccine against Covid-19 already received and the number of SARS- CoV-2 (severe acute respiratory syndrome coronavirus type 2) infections that have gone through. • Vaccination is possible for people who are particularly at risk (BGP) ÿ 16 years of age if the treating doctor considers it to be medically indicated in the respective epidemiological situation in the individual case, a temporarily increased protection against serious illness is to be expected and the last vaccination dose at least 6 months ago (see chapter 3.3). The overarching goals of the vaccination recommendation, based on the vaccination strategy against Covid-19 by Introduction Adjustments since last update 2 initial position 1 Overall goals of the Covid-19 vaccination Implied fragment EKIF Federal Office of Public Health FOPH Federal Department of Home Affairs FDHA Federal Commission for Machine Translated by Google Implied fragment EKIF Federal Office of Public Health FOPH Federal Commission for Federal Department of Home Affairs FDHA have an increased risk of becoming seriously ill with Covid-19 or suffering complications if they are infected with SARS- CoV-2. 5 Since the first appearance of SARS- CoV-2 Omicron in Switzerland in November 2021, In BGP, this protection against serious illness may be less good and depending on the risk factor, e.g. B. with increasing age, lose weight faster. The data available so far show that a further In the case of the omicron subvariants and in particular BA.5, the vaccination protection against any SARS- CoV-2 infection and against mild Covid-19 disease is significantly lower compared to earlier variants and only lasts for a short period of time ([5 – 12]; Kislaya et al, preprint, UKHSA COVID-19 Vaccine Surveillance Reports). Protection from previous SARS- CoV-2 infection against re- infection with BA.4/5 is also reduced. Two studies postulate a certain protective effect of previous infections, especially with earlier omicron subvariants [13, 14]. In contrast, the available data from several countries show that the vaccination and/ or a previous infection protects subvariant BA.5 for at least several months against the occurrence of severe infections including hospitalizations ([3, 15– 17]; UKHSA COVID-19 Vaccine Surveillance Report; Kislaya et al., preprint). Thereafter, this protection gradually decreases (ECDC Technical Report 07/18/22; UKHSA COVID-19 Vaccine Surveillance Reports). In a cohort study with 10.6 million subjects in the USA, Lin et al. observed that the additional protection provided by another booster vaccination decreases after 4-6 months [18]. Further studies from the USA, Canada and Hong Kong show that vaccination protection before hospitalization is still 70-85% 6 months after the booster vaccination ([19– 21]). Data from the UK show that protection against hospitalizations requiring a stay in an intensive care unit (ICU) is still 52% even 12-14 months after a booster vaccination in persons ÿ 65 years (UKHSA COVID-19 Vaccine surveillance report). Based on this data, it can be assumed that the vaccination protects against severe courses for 6 months. Corona Immunitas seroprevalence data shows that in March and June/ July 2022 (after vaccination of the majority of the population and several pandemic waves, most recently delta & omicron waves) > 98% of the population in Switzerland had antibodies against SARS- CoV-2 ([1]; Frei et al., preprint; www.corona- immunitas.ch). This means that almost all individuals have either been vaccinated and/ or recovered from Covid-19 and their immune systems have dealt with SARS- CoV-2 accordingly. The fact of a broad pre- existing immunological confrontation with SARS- CoV-2 antigens, together with the occurrence of SARS- CoV-2 variants, which cause rather mild infections compared to earlier variants, has led to an overall reduction in the burden of the disease and the starting position compared to the Pandemic years 2020/21 changed significantly: People without risk factors have a very low risk of serious illness. Nationally and internationally, how the immunity situation is developing and what significance this development has in terms of protection against individual omicron subvariants or new variants of SARS- CoV-2 is being closely followed nationally and internationally. Most recently, in June 2022, the omicron subvariant BA.5 completely supplanted the preceding BA.2 subvariant and dominated the infection process, and in autumn/ winter 2022/23, along with new subvariants (among others, above all BQ.1, BA.2.75 and XBB) still in circulation at a lower level (CovSPECTRUM). The omicron subvariants are characterized by the fact that, compared to earlier variants, they generally cause milder disease progression and are more immune- vasive and contagious, which means that they can increasingly infect previously vaccinated or recovered people (UKHSA, WHO; [2– 4]; Wang et al., preprint). formed different omicron subvariants, which led to several waves of infection. Immunity situation of the Swiss population Vaccination effectiveness, reinfection risk, disease severity Machine Translated by Google Federal Commission for Federal Department of Home Affairs FDHA Implied fragment EKIF Federal Office of Public Health FOPH Rationale for a Covid-19 vaccination in spring/ summer 2023 Vaccination in older people can increase protection against severe courses (hospitalisation, death) [15, 22– 27]. Because individuals without risk factors are unlikely to be at risk for severe disease, vaccination is not recommended for the general population aged < 65 years, even during an outbreak. Should there be a wave of SARS- CoV-2 outbreaks during the summer season, as occurred in June/ July 2022 as a result of the spread of the BA.5 subvariant, vaccination against Covid-19 is recommended for the BGP (see Chapter 3.3), as they have an increased risk of a severe course of Covid 19. In addition, compared to the general population, vaccination protection in BGP decreases more sharply and more rapidly. A Covid-19 vaccination can increase protection against severe courses for several months (see Chapter 2.3). Detailed information on the effectiveness of the vaccination and the vaccines can be found in Appendix 4. For these reasons, based on the initial situation described in Chapter 2, no recommendation for vaccination against Covid-19 will be made in spring/ summer 2023 (Chapter 3.3). The protein vaccine Nuvaxovid® is less specific to a SARS- CoV-2 variant and therefore triggers a somewhat broader immune response than the monovalent mRNA vaccines and is therefore less dependent on the circulating variant (FDA Advisory Committee Meeting 06/28/22, Novavax). Based on the experience with SARS- CoV-2 over the last three years and the epidemiology of other respiratory viruses, it is a likely scenario that there will be a seasonally low SARS- CoV-2 circulation in spring/ summer 2023. The risk of infection or illness from Covid-19 for the individual and the burden on the health system will therefore be low in the summer season. In contrast to the years 2020 and 2021, with low virus circulation in spring/ summer 2023, hardly any effect of the vaccination on the disease burden in the population can be expected, since over 98% of the population has already had contact with the virus and/ or the vaccine [1], the vaccination can only provide little protection against mild (re)infections and not relevant against virus transmission (see Chapter 2.3). This also applies to people who have not yet been vaccinated against Covid-19, since based on the seroprevalence data it can be assumed that these people have had at least one infection (see Chapter 2.2). The vaccine protection against any, mostly mild infection is primarily mediated by neutralizing antibodies. It is therefore much more dependent on the match between the virus variant used for the vaccine and the virus variant that is spreading than vaccination protection against severe disease progression. The latter is essentially mediated by the T- cell response and reactivated immunological memory that ensure cross- protection across variants [28], and influenced to a much lesser extent by a mismatch between vaccine and circulating variant. Experience over the past year has shown that the adaptation of mRNA vaccines has not kept pace with the rapid and unpredictable evolution of virus variants. The mismatch between the adapted mRNA vaccine and the circulating virus variant leads to significantly lower neutralizing antibody levels against the circulating variant (FDA Advisory Committee Meeting 06/28/22: Moderna; Pfizer). Thus, after vaccination with an adapted or the original vaccine, it cannot be assumed that there is a high level of protection against a mild infection, but protection against a severe infection that is independent of the variant can be assumed. 6 3 Covid-19 vaccination in spring/ summer 2023 Machine Translated by Google Federal Department of Home Affairs FDHA Federal Commission for Implied fragment EKIF Federal Office of Public Health FOPH It is important to emphasize that in the scenario described here, the wave of infection is triggered by a SARS CoV-2 variant, which leads to infections of similar disease severity as the previously and currently circulating omicron subvariants and the vaccines protect against them to a comparable extent (detailed For information on vaccination protection, see Chapter 2.3 and Appendix 4). At this point in time, this seems the most likely scenario. The epidemiological development and in particular the emergence of new virus variants will continue to be closely monitored by the FOPH and EKIF, and the recommendations would be quickly adjusted if necessary. The target group includes all BGP, regardless of the number of doses of vaccine against Covid-19 that have already been received and the number of SARS- CoV-2 infections that have gone through. The target group includes both unvaccinated people and people who have previously been vaccinated against Covid-19. • Persons aged ÿ 16 years with an increased individual health risk due to: Table 1 shows those people who have the highest risk among the BGP. • Individuals aged ÿ 65 years o Pregnancy (see also Chapter 5.3) 7 The particularly vulnerable people (BGP) for severe Covid-19 courses include: o Trisomy 21 Target group- specific vaccination goal: In an epidemiological situation with high virus circulation, vaccination in spring/ summer 2023 offers at least temporarily improved, individual protection against serious illness. The risk of becoming seriously ill with an infection is highest in the BGP group. Vaccination can reduce this risk for at least several months. o Previous illness according to the list of categories Target group: Vulnerable people (BGP) Machine Translated by Google Implied fragment EKIF Federal Office of Public Health FOPH Federal Department of Home Affairs FDHA Federal Commission for vaccination recommendation - Table 1. Previous illnesses/ circumstances associated with the highest risk of severe Covid-19 courses (applies to persons aged 16 and over) respiratory disease kidney disease - Emphysema/ severe bronchiectasis - HIV infection from CD4+ T cell count < 200/ μL FOPH and EKIF only recommend vaccination for BGP ÿ 16 years (see Chapter 3.2 for definition) if the attending physician considers it to be medically indicated in the respective epidemiological situation in the individual case, to expect temporarily increased protection against serious illness and the last vaccination dose was at least 6 months ago (for details on vaccination, see Chapter 3.4). - Diseases with a severely reduced lung capacity heart disease immunodeficiency, - Diabetes mellitus (type 1 or 2) with relevant organ damage; or poorly controlled (HbA1c ÿ 8%) stem cell after The transplant - Individuals with a BMI of ÿ 35 kg/ m² - Chronic heart failure from NYHA II - Liver cirrhosis with a history of decompensation - Condition - Therapy- resistant (> 160 mmHg) hypertension or hypertension with cardiac complications or other end- organ damage congenital or acquired through disease or immunosuppressive therapy organ transplant, Arterial hypertension Diabetes mellitus 8 transplant and people on a waiting list for Pre- existing conditions at highest risk Interstitial Pneumonitis/ Lungenfibrosis obesity - Symptomatic chronic ischemic heart disease despite medical therapy People with trisomy 21 - Severe, chronic renal insufficiency from GFR < 30ml/ min Relevant immunodeficiency at - Chronic obstructive pulmonary disease (COPD) from GOLD II liver disease - malignant haematological diseases - neoplasia/ cancer diseases under active therapy - immune- mediated inflammatory diseases (e.g. systemic lupus erythematosus, rheumatoid arthritis, psoriasis, chronic inflammatory bowel diseases), which receive immunosuppressive therapy (incl. prednisolone equivalent ÿ 20 mg/ day, steroid- sparing therapies and biologics) In principle, the FOPH and EKIF will not formulate a recommendation for vaccination against Covid-19 in spring/ summer 2023 due to the expected low virus circulation and the high level of immunity in the population (see Chapter 2.2) . Machine Translated by Google Implied fragment EKIF Federal Office of Public Health FOPH Federal Department of Home Affairs FDHA Federal Commission for 3.4.1 Bivalent mRNA vaccines 1 4 5 3 2 Should a SARS- CoV-2 wave become apparent in spring/ summer 2023 and the epidemiological situation, according to the assessment of the FOPH and EKIF, requires vaccination of BGP whose last vaccination dose was more than 6 months ago, this will be communicated by the FOPH and EKIF1 and vaccination is therefore generally recommended for this group of people. Bivalent mRNA vaccines contain mRNA for the spike protein of the SARS- CoV-2 strains Original Wuhan and an omicron subtype (BA.1 or BA.4/5). Details on the composition and approval of these vaccines can be found in Appendix 3. These adapted, bivalent vaccines should be used preferentially, since the "mismatch" between the vaccine and the circulating variant is somewhat lower here than with the monovalent vaccines (on the effectiveness of the omicron- adapted Vaccines see Appendix 4). Vaccination consists of a single vaccine dose and is preferably recommended with a bivalent mRNA vaccine3 or Nuvaxovid® 4 . These vaccines, like the monovalent mRNA vaccines5, are generally suitable and recommended to prevent serious infections. A vaccination in spring/ summer 2023 for BGP aged ÿ 16 years should only be administered according to the recommendation described in Chapter 3.3 and no earlier than 6 months2 after the last Covid-19 vaccination dose or 6 months after a known SARS- CoV-2 infection. See Appendix 2 for more information on how to administer the vaccine, see Appendix 3 for properties of the vaccines, and see Appendix 6 for allergy history. 9 Another vaccination (3rd dose) with COVID-19 Vaccine Janssen® is not approved and not recommended for vaccination in spring/ summer 2023. Details on the use of this vaccine can be found in Appendix 7. If vaccination against Covid-19 is required for travel- related reasons, the vaccination schedule according to the approval can be used (2 vaccination doses of a vaccine approved and recommended in Switzerland and, if necessary, a booster vaccination). Travel- related vaccinations are outside the vaccination recommendations of the BAG and EKIF. These recommendations also apply to people who have previously been vaccinated with COVID-19 Vaccine Janssen® (or heterologously with COVID-19 Vaccine Janssen® and an mRNA vaccine) or a vaccine not approved in Switzerland and who have no contraindications for an mRNA - or have protein vaccine. Recommended vaccine and interval for vaccination A homologous booster vaccination with Nuvaxovid® is not approved by Swissmedic (off label) for persons < 18 years of age. The bivalent mRNA vaccines are only approved as booster vaccinations. If the vaccination is the first vaccination dose against Covid-19, the use of the bivalent mRNA vaccines is not authorized by Swissmedic (off- label). In persons < 18 years of age, the booster vaccination is carried out off- label with a bivalent mRNA vaccine. With the bivalent vaccine from Pfizer (Comirnaty® Bivalent Original/ Omicron BA.1), only the 1st and 2nd booster vaccination after primary immunization with Comirnaty® is approved, further booster vaccinations are carried out off- label. Increasing the minimum interval between vaccination and the last vaccination dose resp. known infection from 4 to 6 months is justified by the fact that new scientific evidence shows vaccination protection against severe courses for a period of several months after vaccination (see Chapter 2.3). This corresponds with the recommended intervals in various other countries (e.g. France, UK, Australia). In this case, the present recommendation document will be updated by the FOPH and EKIF and communication will take place via the channels established for the Covid-19 vaccination. In the case of the monovalent mRNA vaccines, only the first booster vaccination is approved, a further booster vaccination with a monovalent vaccine is therefore off- label. Machine Translated by Google Federal Office of Public Health FOPH Implied fragment EKIF Federal Department of Home Affairs FDHA Federal Commission for Comirnaty® Bivalent Original/ Omicron BA.1 vaccine is only for a first or second booster dose after a Primary immunization with Comirnaty® approved for people aged 18 and over. A homologous booster vaccination with Nuvaxovid® is off- label in persons < 18 years of age. 6 7 8 • Bivalent Comirnaty® vaccines: 30 μg dosage The available data show that the monovalent mRNA vaccines used to date continue to provide good protection against severe courses and hospitalizations, even with the current omicron variants ([3, 12, 29-32]; MMWR Report Feb 18, 2022; UKSHA report , May 12, 2022). As a result, they can continue to be used for vaccination as long as they are available. For more information on the effectiveness of mRNA vaccines, see Appendix 4. For individuals < 18 years of age, use of bivalent mRNA vaccines is off- label7. • In principle, the other monovalent mRNA vaccine can also be used than that which was used in the primary vaccination cycle and/ or previous booster vaccination ; however, this corresponds to an off- label application7. The currently published and available data on heterologous Covid-19 booster vaccinations show in particular the interchangeability of mRNA vaccines [33-37]. The obligation to provide information must be observed, and the usual liability rules apply (see BAG off- label use). Vaccination with a bivalent mRNA vaccine can also be heterologous, ie after the primary vaccination course and/ or previous booster vaccination with another approved vaccine against Covid-19. The bivalent vaccine from Pfizer (Comirnaty® Bivalent Original/ Omicron BA.1) is a heterologous booster vaccination for use outside of Swissmedic approval (off- label)6, 7. • Spikevax®: 50 μg dosage • Dosage: 5 μg recombinant spike protein • Comirnaty®: 30 μg dosage For people aged ÿ 16 years, all available bivalent mRNA vaccines are equally suitable for the booster vaccination (exception: people with severe immunodeficiency, see Chapter 5.1.4.1). Vaccination can be carried out both homologously8 and heterologously with the protein vaccine Nuvaxovid® . Due to the less variant- specific immune response compared to the monovalent mRNA vaccines, the use of Nuvaxovid® is recommended in preference to the monovalent mRNA vaccines. Information on the composition of the vaccine can be found in Appendix 3 and on efficacy in Appendix 4. 10 • Bivalent Spikevax® vaccines: 50 μg dosage • Both available monovalent mRNA vaccines are equally suitable for vaccination for all persons aged ÿ 16 years (exception: persons with severe immunodeficiency, see Chapter 5.1.4.1). 3.4.2 Protein vaccine Nuvaxovid® 3.4.3 Monovalent mRNA vaccines Machine Translated by Google Implied fragment EKIF Federal Office of Public Health FOPH Federal Commission for Federal Department of Home Affairs FDHA 9 • Vaccination with a monovalent mRNA vaccine, provided it is the fourth (fifth or sixth for certain target groups) dose, is not authorized by Swissmedic (off- label)9 . See Appendix 2 for information on how to carry out the vaccination, see Appendix 3 for properties of the vaccines, see Appendix 6 for procedures in the event of an allergy history. Pain at the injection site, tiredness, muscle pain and headache (see prescribing information). In observational studies , very rare cases of myo-/ pericarditis were also observed with Nuvaxovid® (TGA COVID-19 vaccine safety report 10/20/22). The obligation to provide information must be observed. The usual liability rules apply (see BAG off- label use). 11 The safety and tolerability of the protein vaccine Nuvaxovid® was demonstrated in the pivotal studies. The most frequently observed UIE after vaccination with Nuvaxovid® are sensitivity or According to the current state of knowledge, the risk of severe UIE with a recommended vaccination is much lower than the risk of a complication from Covid-19, against which the vaccination protects. The benefit of the vaccination administered according to the recommendation therefore outweighs the possible risks. The latest developments and findings in this regard are closely monitored by the responsible authorities. The group at risk of severe disease progression (BGP) also includes people with a severe weakness of the immune system (severe immunodeficiency). The immune deficiency can be congenital, acquired or caused by drugs that suppress the immune system (e.g. chemotherapy, treatment of autoimmune diseases or after transplantations). According to numerous clinical and observational studies, the mRNA vaccines against Covid-19 are well tolerated, but can be associated with mild to moderate UIE, which usually resolves within a few days. The most frequently observed UIE are local pain at the injection site, fatigue and headache [38, 39]. Anaphylactic reactions [40] and myocarditis/ pericarditis [41– 43] (see Appendix 5) are very rare, severe UIEs after vaccination with mRNA vaccines that have been observed after approval. Medical professionals should report observed UIE or suspected cases of UIE from the Covid-19 vaccines to Swissmedic (via the ElViS online tool). According to Art. 59 of the Therapeutic Products Act (HMG), there is a reporting obligation, particularly for reports of serious and/ or previously unknown UIE. Detailed explanations of the UIE can be found in Appendix 5. 4 Adverse Vaccination Symptoms (UIE) 5 Procedure for special groups of people Individuals with severe immunodeficiency Machine Translated by Google 5.1.1 Definition of severe immunodeficiency 5.1.2 Vaccination response to Covid-19 mRNA vaccines in severe immunodeficiency caused by immunosuppressive treatments The vaccination could possibly protect against severe courses due to the T cell response. Thus, people with B- cell- depleting therapies show T- cell responses after vaccination [60]. • B- cell depleting therapy (e.g. rituximab, ocrelizumab, cyclophosphamide) • Patients with HIV infection and CD4+ cells < 200/ μL However, scientific data indicate that vaccination with two doses of mRNA vaccine in severely immunocompromised individuals elicits decreased T cell responses [53], but a third dose of Covid-19 mRNA vaccine may improve vaccination response in transplanted individuals [ 52, 61]. The improved immune response after a third dose of vaccination in severely immunocompromised individuals with low antibody production is consistent with experience with vaccines against other pathogens. • Patients on dialysis (hemodialysis and peritoneal dialysis) • High- dose chemotherapy 12 • Patients with other diseases that are of comparable severity • Corticosteroid therapy ÿ 20 mg prednisone equivalents/ day for > 2 weeks • Combination therapy of various immunosuppressive drugs accompanied by immunodeficiency • Other therapies that lead to severe immunosuppression (e.g. mycophenolate, ciclosporin, Janus kinase inhibitors, etc.) • People before or after solid organ transplantation As well as People who were under one of the following severe immunosuppressive treatments at the time of the Covid-19 vaccination or who have one of the following are considered to be severely immunodeficient • Persons with a congenital immunodeficiency with restricted B and T cell function (e.g. Under treatment with biologics that block cytokines (eg, anti- tumor necrosis factor- ÿ, anti- interleukin-6) or mild immunosuppression, vaccinated individuals usually form protective antibodies after vaccination [44-47]. On the other hand, this antibody formation can occur in people who are due to a transplant [48– 53], autoimmune diseases [46, 54, 55] or cancer (e.g. leukemias [56– 59]) are treated with a therapy that severely weakens the immune system, be limited or completely absent. Common Variable Immunodeficiency CVID, isolated CD4 lymphocytopenia, etc.) diseases suffered: Studies in these populations show that treatments that suppress B cells (e.g., rituximab, ocrelizumab, cyclophosphamide), chemotherapy, Bruton tyrosine kinase inhibitors, high- dose corticosteroid therapies, or other strong immunosuppressive therapies (e.g., mycophenolate , Janus kinase inhibitors, combination treatments) may be associated with poor or absent antibody formation after two doses of Covid-19 mRNA vaccination. In particular, a relevant proportion of vaccinated transplanted persons do not form antibodies. To date, little is known about the protection of vaccination in the absence of vaccine antibodies, and a serological correlate of protection is unknown. Federal Commission for Federal Department of Home Affairs FDHA Federal Office of Public Health FOPH Implied fragment EKIF Machine Translated by Google For severely immunodeficient people aged 16 and over who have already been vaccinated against Covid-19, the recommendation for a Covid-19 vaccination applies as it applies to BGP and is described in Chapter 3.3. 13 If immunosuppressive therapy or the intensification of an existing immunosuppressive therapy is planned, prior vaccination with one dose is recommended. 4 weeks after vaccination, a serology should be used to assess whether vaccination protection has been built up10. There is no minimum time interval between vaccination and therapy (no live vaccine), but 'the longer the interval, the better'. • Vaccinations should preferably be carried out during a stable phase of the disease. If this is not possible, it is recommended to wait for currently active inflammatory diseases. Here, the benefits of the vaccination must be weighed against the risks of the vaccination, since symptoms after the vaccination are difficult to attribute to the vaccination or the disease. For the reasons given in Chapter 5.1.2, a 3- dose vaccination scheme with an mRNA vaccine11, 12 is recommended for the primary immunization of severely immunodeficient persons , the minimum interval between the individual doses is 28 days. It is recommended that vaccinations preferably be carried out with a bivalent mRNA vaccine13. The bivalent as well as the monovalent mRNA vaccines are basically suitable and recommended to prevent serious infections. Data on vaccine efficacy and safety in people with severe immunodeficiency come from observational studies, not pivotal studies. Immunodeficiency [62– 66]: Initiation phase of immunosuppression with high doses of glucocorticosteroids (prednisone equivalent ÿ 20 mg/ day > 2 weeks in adults) or in the first three months after B cell- depleting therapy (e.g. rituximab, ocrelizumab), since the vaccine response in these situations is presumably restricted to such an extent that protection is scarcely achieved. The same recommendations apply as for other vaccinations in people with severe For severely immunodeficient people who have not yet been vaccinated against Covid-19, the recommendations described below apply. • Waiting before vaccination is generally recommended in the case of severe immunosuppression, e.g. B. Federal Office of Public Health FOPH Implied fragment EKIF Federal Commission for Federal Department of Home Affairs FDHA • 5.1.3 Vaccination timing in severe immunodeficiency 5.1.4 Vaccination schedule for persons with severe immunodeficiency Bivalent vaccines are only approved as booster vaccinations. It is used off- label for primary immunization and there is little data on it. In the EU, the use of bivalent vaccines for primary immunization with 2 vaccine doses has been possible since December 2022 (EMA). 5.1.4.1 Primary immunization (3 doses) 12 13 10 11 So far there is no serological protective correlate and no standardization of the various antibody tests (ECDC). For Inactivated vaccines are equally well tolerated by people with and without immunodeficiency. With the antibody test used (which should have been evaluated against neutralizing antibodies), the measured antibody concentration of SARS- CoV-2 S IgG should be in the clearly positive range of sera from convalescent people. Since mRNA vaccines are not live vaccines, they may be given in the case of immunosuppression. Basically become If a severely immunodeficient person aged 12 and over cannot be vaccinated with an mRNA vaccine for medical reasons, vaccination with Nuvaxovid® can be considered (2 doses of vaccine 4 weeks apart for previously unvaccinated individuals) if the potential benefit is determined by an individual The benefit- risk assessment clearly predominates. Machine Translated by Google The reduced dosage of 50 μg Spikevax® is recommended, as it can be assumed that even severely immunodeficient people have already had contact with SARS- CoV-2 (see Chapter 2.2). The use of half the dose of Spikevax® (booster dosage) in primary immunization is off- label. So far there is no serological protective correlate and no standardization of the various antibody tests (WHO standardization should follow). For the antibody test used (which should have been evaluated against neutralizing antibodies), the measured antibody concentration of SARS- CoV-2 S IgG should be in the clearly positive range of sera from convalescent people. vaccination dose required. Borderline positive vaccine antibody titers are to be considered negative. In the event of negative detection of SARS- CoV-2 vaccine antibodies, a 3rd dose for primary immunization with a minimum interval of 4 weeks after dose 2 is recommended. This more limited recommendation is made because a 3rd dose is off- label at this age, little data is available and therefore only children whose antibody titers indicate incomplete immunization protection should receive a 3rd dose. • Dosage for the basic immunization with 3 doses of an mRNA vaccine: A dose of 30 μg each for the Comirnaty® vaccines resp. 50 μg recommended for the Spikevax® vaccines14 (these dosing recommendations apply to both the bivalent and monovalent mRNA vaccines). A minimum interval of 4 weeks is recommended between the individual vaccine doses , regardless of the values from previous antibody determinations. • Children aged 5-11 years with severe immunodeficiency are recommended to be vaccinated with Comirnaty® 10 μg (children's vaccine) . Serology15 is recommended 4 weeks after the 2nd vaccination dose . If there are clearly positive SARS- CoV-2 vaccine antibodies, no 3rd • The 3rd dose should be given as soon as possible if the 2nd dose was administered more than 4 weeks ago. The ideal time to administer the 3rd dose should be discussed with the attending specialists (minimum interval of 4 weeks after the 2nd dose). In general, immunosuppression at the time of vaccination should be as low as possible if the treatment of the disease allows it. With therapies that deplete B cells, care should be taken not to administer the vaccine at a time when B cells are fully suppressed. In people with B- cell depletion (rituximab, ocrelizumab, etc.), the 3rd mRNA vaccination dose should ideally be given 4-5 months after the last dose of the B- cell- depleting drug and at least 4 weeks before the next dose in order to to enable the best possible B cell response. • Comirnaty® (bivalent or monovalent) (3 doses) is recommended as a preference for persons with severe immunodeficiency aged 12-29 years , see Appendix 5 for further details. For persons in this group who have been vaccinated with one or two doses of Spikevax® , the basic immunization can be completed heterologously with Comirnaty® (off- label) after consultation with a specialist according to an individual benefit- risk assessment . 14 • Vaccination after known SARS- CoV-2 infection: An infection does not replace a vaccination dose, the vaccination series should be started/ continued taking into account the minimum interval of 4 weeks (primary immunization) after infection. If monoclonal antibodies have been administered for therapy (or prophylaxis), a SARS- CoV-2 vaccination should be postponed by at least 3-6 months (recommendations for the early use of Covid-19 therapies and for prophylaxis, Swiss Society for Infectious Diseases). Comirnaty® and Spikevax® are equally suitable for people over the age of 30 . 14 15 Implied fragment EKIF Federal Office of Public Health FOPH Federal Commission for Federal Department of Home Affairs FDHA Machine Translated by Google Implied fragment EKIF Federal Office of Public Health FOPH Federal Commission for Federal Department of Home Affairs FDHA 5.1.5 Vaccination antibody determination in persons with severe immunodeficiency 5.1.4.2 Booster vaccination Primary immunization with Comirnaty® approved for people aged 18 and over. So far there is no serological protective correlate and no standardization of the various antibody tests (WHO standardization should follow). The antibody determination is intended to determine whether a person has come into contact with SARS- CoV-2 antigens and whether there is a possible immunological protection