Skip to main content

Updated recommendations of the German Society for Rheumatology for the care of patients with inflammatory rheumatic diseases in the context of the SARS-CoV-2/COVID-19 pandemic, including recommendations for COVID-19 vaccination

Aktualisierte Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie für die Betreuung von Patienten mit entzündlich-rheumatischen Erkrankungen im Rahmen der SARS-CoV-2/COVID-19-Pandemie einschließlich Empfehlungen zur COVID-19-Impfung

Core recommendations

Table 1.

Table 1 Core recommendations of the DGRh for the care of patients with inflammatory rheumatic diseases in the context of the SARS-CoV-2/COVID-19 pandemic

1 Introduction

Even after more than one year, the COVID-19 pandemic is a great challenge for patients with inflammatory rheumatic diseases (IRD) as well as for rheumatologists. The recommendations of the German Society for Rheumatology (Deutsche Gesellschaft für Rheumatologie e. V.; DGRh) of March 2020 were intended to provide initial, rapid guidance on specific concerns in the care of patients with IRD in the face of the threat posed by SARS-CoV‑2. These were based primarily on expert consensus [1,2,3]. The first update in July 2020 [4, 5] already relied on scientific data from registries, cross-sectional studies, case reports, and case series [6, 7]. In the meantime, we have further results from scientific publications on COVID-19 in IRD, from which much more precise statements on disease- or therapy-related risks can be derived. An important reason for updating the recommendations for action again is the fact that vaccinations against SARS-CoV‑2 are now available and are thus increasingly being administered to patients with IRD. This raises many questions, also and especially for patients with IRD, but also for the physicians and medical professionals caring for them.

2 To whom should these recommendations apply?

The statements and recommendations made here refer to patients with inflammatory rheumatic diseases (IRD), especially in consideration of the medicinal antirheumatic therapy. Where appropriate or necessary, comparisons are also made with SARS-CoV‑2 infections and COVID-19 in the general population. The statements have to be relativised—at least partially—for IRD patients who have been vaccinated against COVID-19 or who are protected after a SARS-CoV‑2 infection. However, there is still no clarity as to whether and how a vaccination’s success or protection after a previous infection can be investigated with sufficient reliability and when booster vaccinations may be necessary. It should also be pointed out that these recommendations cannot cover all situations that justify or even suggest a deviation from them in individual cases.

3 What is the risk for patients with IRD for infection with SARS-CoV-2 and a severe course of COVID-19?

An idea of the significance of age for the risk of COVID-19 for hospitalisation and death, also in relation to various concomitant diseases, is given in Fig. 1 in the appendix from a comprehensive so-called “Umbrella Review” of the Robert Koch Institute (RKI) [8].

3.1 General risk factors for COVID-19 and a severe course

Risk factors in the general population for a severe course of COVID-19 (Table 2; [9]) also apply to patients with IRD [10,11,12,13,14,15,16,17,18,19,20].

Table 2 General risk factors for a severe course of COVID-19

3.2 Specific risk factors of inflammatory rheumatic diseases for SARS-CoV-2 infection and severe course of COVID-19

3.2.1 Risk for infection

Whether patients with IRD have an increased risk of COVID-19 compared to the normal population is not conclusive. While some studies report an increased risk of COVID-19 compared to the normal population or compared to a “matched” population without IRD in certain patient populations, e.g. in patients with systemic sclerosis [20,21,22], others indicate a comparable risk to the normal population [23,24,25].

3.2.2 Risk of a severe course

Current data from registries and a meta-analysis [20] mostly confirm results from early case series [26], according to which the risk of a severe course (defined here and in the following as inpatient admission and/or the need for ventilation and/or death) is generally not increased in patients with IRD in total compared to the normal population or compared to “matched” cohorts without IRD. As in the normal population, the risk is increased above all in the presence of comorbidities [12,13,14,15, 27]. Only a few cohort studies found an enhanced risk for a severe course in patients with rheumatoid arthritis [28, 29] or in the total cohort of IRD patients compared to the normal population or to “matched” cohorts without IRD. These publications show a high proportion of patients with connective tissue disease and vasculitides (Table 5 in the appendix), which could possibly contribute to a more severe course (see [28]). Subgroup analyses from recent registry and cohort studies support this finding: systemic diseases such as vasculitides, SLE, systemic sclerosis, Sjögren’s syndrome, as well as autoinflammatory diseases possibly carry a higher risk for a severe COVID-19 course or death compared to the normal population or a matched non-IRD population or rheumatoid arthritis used as a reference [12, 13, 18, 19, 28,29,30]. When interpreting these data and drawing conclusions from them, it must be taken into account that only relatively small numbers of cases of these IRD subpopulations have been recorded in the registries and cohort studies to date. It is also unclear whether the increased risk for a severe course is caused by the disease itself or by certain organ involvement (e.g. lung or kidney involvement) or the intensity of immunosuppression.

In analyses from the German and global COVID-19 registries, high disease activity of the respective IRD was clearly identified as a risk factor for a severe course of COVID-19, with an odds ratio (OR) of 1.96 (95% confidence interval [CI] 1.02–3.76) and 1.87 (95% CI 1.27–2.77), respectively, compared to patients with low or no disease activity [14, 15].

4 Influence of immunosuppressive/immunomodulatory drugs on the course of COVID-19

4.1 Glucocorticoids

Long-term therapy with glucocorticoids (GC) is a known risk factor for infections and also for a more severe course of infections in IRD [31, 32]. Cohort studies and registry data have shown that this also applies to COVID-19: Therapy with GC was already associated with an increased COVID-19 infection rate from a dose of 2.5 mg daily in a large northern Italian cross-sectional study of over 2000 IRD patients [33]. GC use at doses of 10 mg (prednisone equivalent) daily and above resulted in an increased risk of severe COVID-19 compared with a matched non-IRD population at an OR of 1.97 (95%CI 1.09–3.54) in a cohort study of 694 patients with IRD [13]. In the global registry study of 3729 IRD patients, the OR for COVID-19-associated mortality was 1.7 (95%CI 1.18–2.41) for GC above 10 mg daily versus no systemic GC intake [15]. In the German registry of 468 IRD patients, the OR for GC > 5 mg was 3.67 (95%CI 1.49–9.05) versus no glucocorticoid therapy [6].

The interpretation of this risk increase must be made with caution since an increase in the glucocorticoid dose in most cases occurs due to increased disease activity leading to “confounding by indication”. In a further evaluation of the global registry, it could be shown that in remission or low disease activity, even GC in a dosage of > 10 mg daily versus no glucocorticoid therapy are not associated with a higher risk of a more severe course or death [34]. Therefore, the data suggest that higher disease activity is the main risk factor compared to the GC dose, but since the strength of the association with a more severe course within the subgroups of different disease activity increased with higher GC doses, it cannot be ruled out that GC exert an additional negative influence.

4.2 Conventional DMARDs, immunosuppressants, and immunomodulators

In the analysis of the global IRD registry with data up to July 2020, ongoing therapy with immunosuppressants overall (azathioprine, cyclophosphamide, ciclosporin, mycophenolate, tacrolimus) was significantly associated with a lethal outcome of COVID-19 with an OR of 2.22 (95%CI 1.43–3.46), as was therapy with sulfasalazine with an OR of 3.6 (95%CI 1.7–7.8) [15]. In the French registry, of the immunosuppressants, mycophenolate was conspicuous for a severe course (ventilation or death) with an OR of 6.6 (95%CI 1.47–29.6), while no signal was found for methotrexate, leflunomide, and azathioprine (although the number of cases for azathioprine was very small) [13]. In the evaluation of the global registry, “no DMARD therapy” was also associated with an increased OR for a lethal course of 2.11 (95%CI 1.48–3.01) compared to methotrexate monotherapy. In the aforementioned northern Italian cohort study, there was no increased risk of COVID-19 infection either in the group of conventional synthetic DMARDs (csDMARDs) or in the group of biological or targeted DMARDs (b/tsDMARDs), although an analysis by individual substances was not carried out [33].

4.3 Biologics and JAK inhibitors

There is increasing evidence that B‑cell depletion, or possibly only significant hypogammaglobulinemia, are risk factors for a severe course of COVID-19. Initially, individual cases were reported [35,36,37,38] of a more severe course of COVID-19 after or during therapy with rituximab. Rituximab therapy was significantly associated with a fatal course of COVID-19 in the global COVID-19 registry on IRD [15] with an OR of 4.04 (95%CI 2.32–7.03) and in the French registry [13] with an OR of 4.21 (95%CI 1.61–11.0). In another analysis of the French registry [39], a total of 137 (13%) severe courses and 89 (8%) deaths were found in 1090 patients with IRD (mean age 55 ± 16 years; 734 [67%] female). Of 63 patients treated with rituximab, 13 (21%) died compared to 76 (7%) of the 1027 patients without rituximab. Although the risk of death adjusted for the above-mentioned parameters was not significantly increased in the rituximab group (effect size 1.32, 95% CI 0.55–3.19, p = 0.53), severe courses were significantly more frequent with rituximab (n = 22) than in the control group (n = 115), even after adjustment (effect size 3.26, 95% CI 1.66–6.40, p = 0.0006).

The Global Rheumatology Alliance (GRA) evaluated 2869 of 6132 RA patients in the global COVID-19 registry (as of mid-April 2021) who were on treatment with the biologics abatacept (n = 237), rituximab (n = 364), IL-6R inhibitors (n = 317), TNF inhibitors (n = 1388) or JAK inhibitors (n = 563) at the time of infection. A higher rate of treatment with TNF and IL-6R inhibitors was found in nonhospitalised RA patients and a higher rate of treatment with rituximab in oxygen-dependent and deceased RA patients; the rate of treatment with JAK inhibitors was also slightly higher. In multivariate analysis adjusted for age, sex, region, season, obesity, smoking, csDMARDs, GC (±/dose), disease activity and the number of comorbidities, the OR for a severe course of COVID-19 versus treatment with TNF inhibitors was 4.15 (3.16–5.44) for rituximab and 2.06 (1.60–2.65) for the JAK inhibitor group [40]. Whether a protective effect of TNF or IL-6R inhibitors concerning severe courses of COVID-19 may also play a role here cannot yet be answered. Patients under TNF inhibitors were chosen as a reference in the multivariate analysis, and patients under IL-6R inhibitors did not show any difference. It should be mentioned, however, that even among the 571 patients treated with TNF blockers in the German registry so far, only two fatal courses of COVID-19 were recorded and the number of hospitalised cases was comparatively low at 52 patients (as of 23 May 2021). However, it must be taken into account that patients treated with TNF inhibitors were on average younger (53 vs. 59 years), received GC less frequently, and had less disease activity compared to patients not treated with TNF blockers.

In summary, due to an increased risk of a more severe course of COVID-19 during therapy with rituximab, we recommend that this therapy be carefully weighed up about possible alternatives or concerning the individual benefit and risk. Otherwise, the risk of increased disease activity for a severe course of COVID-19 is estimated to be higher than the risk of a severe course due to antirheumatic therapy. It is therefore not recommended to discontinue or reduce antirheumatic therapy as a precaution. Even a therapeutically necessary glucocorticoid dose should not be changed out of concern for a more severe course of COVID-19.

5 Prevention of infections and protective measures

Common behavioural and precautionary measures described and regularly updated by the Robert Koch Institute [41] and the Federal Centre for Health Education [42] for the general population and for persons at special risk apply. Special measures going beyond this are not recommended.

Weighing up the benefits and risks, there is no need to avoid visits to the doctor intending to reduce the risk of infection. Necessary inpatient treatment should not be delayed.

Appropriate behavioural and hygienic measures must continue to be ensured in out- and in-patient settings. Intelligent planning of consultation hours should be carried out (e.g. short waiting times, observance of distance rules, wearing of mouth and nose protection masks, minimisation of the number of accompanying persons, generous ventilation).

To prevent the spread of infection, patients should be informed in advance not to attend unannounced health facilities with symptoms of illness or after contact with people who are known to be infected with SARS-CoV‑2. In such cases or after a stay in a high-risk or virus variant area (“variants of concern”), the practice should first be contacted by telephone.

Typical COVID-19 symptoms (see Table 6 in the appendix) or contacts to infected persons can be asked for in advance. In case of doubt, adequate testing is recommended. To break chains of infection and contain new possible waves of infection, patients can be advised to use the “Corona warning app” or comparable digital applications [43].

According to the recommendations of the Standing Commission on Vaccination (STIKO) of the Robert-Koch-Institute (RKI), the vaccination status should be updated: In addition to SARS-CoV‑2 (see section 8), this primarily concerns vaccinations against pneumococci and influenza.

6 Antirheumatic therapy in the context of SARS-CoV-2 or COVID-19

In principle, rheumatologists should always be involved in the decision to maintain, reduce or pause antirheumatic therapy in the context of COVID-19. Counseling regarding antirheumatic therapy should be performed in a shared-decision manner between doctor and patient even in the context of the COVID-19 pandemic. To further improve the data situation, it is recommended that patients with IRD and COVID-19 (detected through positive PCR, rapid antigen test, or antibody test for SARS-CoV-2) are documented in the COVID-19 register of the DGRh (

The following specific recommendations continue to apply:

6.1 Patients without signs of infection

6.1.1 Existing antirheumatic therapy

  • Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), conventional synthetic DMARDs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), biologic DMARDs (bDMARDs) and immunosuppressants (see section 4.2) should be continued unchanged as indicated by the IRD and should not be discontinued or reduced for fear of SARS-CoV‑2 infection alone. The GC dose should be kept as low as possible—as is valid for all situations in IRD therapy—and a necessary increase above 10 mg daily should be accompanied by consistent protective measures.

  • In the case of therapy with rituximab (RTX) in indications without potentially life-threatening manifestations, especially in uncomplicated RA in sustained remission, a postponement of RTX administration should be considered, also to enable a potentially more promising vaccination of the patient (see section 8). This should be done after weighing the risk of relapse against the individual risk of infection. Under no circumstances should the use of RTX for remission induction be delayed in cases of systemic diseases that pose a serious threat, e.g. ANCA-associated vasculitis (AAV).

6.1.2 Restarting or changing antirheumatic therapy

  • The start of antirheumatic therapy should not be omitted or delayed because of the COVID-19 pandemic; the dose should follow the usual recommendations.

  • A recommendation for or against a specific DMARD (for RTX see next point in the list) cannot currently be made for new patients.

  • In the case of valid alternatives (e.g. in RA), the use of RTX should be critically questioned because of possible favouring a more severe course of COVID-19 (see section 4.3), the long B‑cell depletion, and limited vaccination response. However, the use of RTX for remission induction in systemic diseases (e.g. in AAV) should not be omitted in concern of COVID-19.

  • Protocols with reduced GC administration, e.g. in giant cell arteritis or AAV should be preferred [44, 45].

6.2 Patients with contact to SARS-CoV-2 positive persons and without own COVID-19 infection signs

  • The therapy should be continued as described in section 6.1. If symptoms occur, a doctor or rheumatologist should be contacted (see section 6.3).

6.3 Patients with signs of infection after contact with SARS-CoV-2 positive persons

  • A change in therapy should not be made if symptoms are mild and fever is absent.

  • If there are clear signs of infection and especially fever (> 38 °C), the antirheumatic medication should be paused.

  • GC therapy ≤ 10 mg prednisolone equivalent daily can be continued; for higher doses, the continuation of GC treatment must be decided on an individual basis.

6.4 Patients tested positive for SARS-CoV-2 and without signs of COVID-19 infection

  • Pausing or delaying ts- or bDMARD therapy for the duration of the mean incubation period may be considered. As it is often not known when an infection has occurred, a pause for 5–6 days after smear may be considered if symptom-free conditions persist.

  • GC therapy ≤ 10 mg prednisolone equivalent daily can be continued; at higher doses, the continuation of GC treatment must be decided on an individual basis.

  • csDMARDs should not be discontinued.

6.5 Patients tested positive for SARS-CoV-2 and with signs of COVID-19 infection

  • GC therapy ≤ 10 mg prednisolone equivalent daily can be continued; for higher doses, the continuation of GC treatment must be decided individually.

  • DMARDs should be paused in this situation (leflunomide should be washed out, if necessary, because of the long half-life of this compound).

  • In patients at risk for severe COVID-19 progression (e.g. severe immunosuppression with active IRD, primary immunodeficiencies), early passive immunisation with a combination of two neutralising monoclonal antibodies should be considered according to the COVRIIN/STAKOB/DGI statement (for current information including link to the list of therapy centres see [46] or explanation in the supplementary online information).

7 Proof of past infection with SARS-CoV-2

With the duration of the pandemic, the proportion of patients who have been exposed to SARS-CoV‑2 increases, regardless of whether COVID-19 symptoms were present. In the future, it may become important to be able to estimate the individual risk of infection by knowing the patients’ (possibly protective) immune status against SARS-CoV‑2. At present, due to lack of data on antibody formation and persistence and the importance of T‑cell immunity, especially under immunosuppression, and due to limited or unclear specificity and sensitivity of the different test methods, no recommendation can yet be made for screening patients with IRD for antibodies. A general screening before vaccination in the absence of clinical evidence of a previous infection is not recommended.

Furthermore, it cannot be assessed at present whether the risk of re-infection or contagiousness is reduced if IgG antibodies against SARS-CoV‑2 are detected. Thus, even in the case of a positive antibody test, it is not recommended to loosen the measures for infection and foreign infection prophylaxis.

8 Vaccination against COVID-19

8.1 Introduction

Despite worldwide efforts to develop effective drugs for the treatment of COVID-19, there is as yet no therapeutic option that promises a cure with sufficient certainty. Thus, vaccination of large parts of the population as soon as possible is considered the decisive step to contain the pandemic [47].

Also for the accelerated assessment and approval procedures of the COVID-19 vaccines by the EMA, the safety standards required for approval applied without restriction [48]. Currently, four SARS-CoV‑2 vaccines are available in Germany [49]. These are two messenger RNA (mRNA) vaccines and two vector vaccines (Table 3).

Table 3 COVID-19 vaccines licensed in the EU (as of 15 May 2021)

Patients with known or suspected immune dysfunction were excluded from the phase III trials of the vaccines, but because “healthy adults and those with stable pre-existing conditions” could be included [8], the pivotal trials with more than 43,000 [50] and more than 30,000 [51] subjects included also some with IRD [25].

Based on this situation, the DGRh had published the first recommendations for vaccination of patients with IRD or under immunomodulating therapies against SARS-CoV‑2 in IRD and subsequently updated them (online) several times. These recommendations could not be based on studies on the safety and efficacy of SARS-CoV‑2 vaccines in IRD patients so far but were consented based on findings with other vaccinations in IRD patients among the experts of the COVID-19 commission of the DGRh [52,53,54]. In addition to a continuous literature search, national [8, 47, 49] and international recommendations of other professional societies [55, 56] were also taken into account.

8.2 Type of vaccines and inflammatory rheumatic diseases

None of the vaccines against SARS-CoV‑2 approved so far is a live vaccine. Therefore, all of them can be administered to patients with IRD, even under immunosuppressive/immunomodulatory therapy. Apart from extremely rare allergies to vaccine components, there are no contraindications to COVID-19 vaccination.

8.3 Vaccination against COVID-19 during pregnancy and lactation

From an ongoing study of more than 35,000 pregnant women vaccinated against COVID-19 with mRNA vaccines, a first interim evaluation of 827 completed pregnancies was carried out, in which no significant safety signals were seen [57]. The STIKO does not currently make a general vaccination recommendation for pregnant women. Pregnant women with previous illnesses and a resulting high risk of severe COVID-19 disease or with an increased risk of exposure due to their life circumstances can be offered vaccination with an mRNA vaccine from the 2nd trimester onwards after a risk–benefit assessment and detailed medical information [49]. The German Society for Gynaecology and Obstetrics recommends (as of 05/2021) that pregnant women are vaccinated with mRNA-based vaccine against COVID-19 in an informed participatory decision-making process and after exclusion of general contraindications [58]. To protect pregnant women indirectly, the prioritised vaccination of close contacts of pregnant women, especially their partners, as well as midwives and doctors, is also recommended. mRNA-based vaccination against COVID-19 should be offered and made available to breastfeeding women.

8.4 Are there differences in the effectiveness of COVID-19 vaccines?

The vaccines approved in Germany by BioNTech/Pfizer, Moderna, AstraZeneca, and Janssen (Johnson & Johnson) all offer protection against symptomatic infections. The efficiency data in the prevention of all infections determined by the clinical trials as percentages only reflect the effectiveness to a limited extent. All vaccines approved to date can largely prevent severe courses and deaths [49]. Current data on the vaccines can be found on the website of the Paul Ehrlich Institute (PEI) (

8.5 Efficacy of vaccines against SARS-CoV-2 variants

All vaccines licensed in Europe are considered to provide very good protection against symptomatic disease not only against the original “wild type” of SARS-CoV‑2 but also against the alpha (B.1.1.7) and delta (B.1.617.2) variants currently prevalent in Germany, although a complete vaccination series seems to be important for protection against the delta variant [49].

8.6 To what extent does an inflammatory rheumatic disease or immunosuppressive/modulatory therapy change the entitlement to COVID-19 vaccination?

According to the Corona Vaccination Ordinance (CoronaImpfV) of the Federal Ministry of Health, patients with rheumatic diseases have so far been entitled to be vaccinated with increased priority, and in the case of certain organ manifestations also with high priority [59]. Concerning changes or cessation of prioritisation, reference is made to the current Corona Vaccination Ordinance in the official “Bundesanzeiger”, the recommendations of the Robert Koch Institute, and the website of the DGRh. Even if prioritisation is discontinued, the DGRh would like to point out that patients with IRD should continue to be vaccinated preferentially.

8.7 Tolerance of vaccinations in rheumatic diseases

On the question of the tolerability of COVID-19 vaccinations in patients with IRD, an online survey of 325 patients [60] and two first prospective German studies with 29 and 84 patients [61, 62] have been published so far. Overall, good tolerability and no specific intolerance reactions were observed. However, only mRNA vaccines were used in all these studies. With more than 1.4 billion vaccinations administered worldwide (as of 15 May 2021) [63], there is currently no evidence that patients with IRD have a different spectrum of side effects or increased adverse reactions to the currently approved vaccines than the normal population. In principle, there is a recommendation not to administer elective vaccinations during a disease flare, but whether vaccination against COVID-19 should be made at all dependent on actual disease activity is controversial [55, 56].

8.8 Can COVID-19 vaccination trigger a flare of rheumatic diseases?

Theoretically, vaccines, like infections, could trigger relapses of known or even initial manifestations of IRD. This is not yet known for the currently approved vaccines against COVID-19. According to current knowledge, the benefit of vaccination clearly outweighs the theoretical risk of a usually only slight or temporary activation of the underlying disease. Studies on other vaccines showed no evidence that they trigger flares of IRD [64, 65]. In the first German study mentioned above, no effect on the activity of the underlying disease was found in association with the mRNA vaccination against SARS-CoV-2 [61]. Even if in individual cases “relapses” can occur in the context of the (desired) vaccination response, which can generally be controlled with symptomatic therapy, there are no hints for permanent activation of an IRD by vaccination against SARS-CoV‑2. Therefore, concerns about the worsening of an IRD are no reason to refrain from vaccination.

8.9 Is there a vaccine to prefer for rheumatic diseases or immunomodulatory medication?

The STIKO does not derive any preference for a specific vaccine for the German population from the data available to date on the effectiveness of the available vaccines with regard to the virus variants known to date but assumes that all vaccines available to date are equally suitable for combating the pandemic [49].

No significant differences in the safety of these vaccines can be inferred from the controlled trials. Postmarketing surveillance for the AstraZeneca vaccine showed evidence of very rare immunologically mediated events, predominantly in younger female patients with thrombocytopenia, coagulation disorders, and unusual thromboses, including sinus vein thrombosis [66,67,68]. The EMA sees a probable connection with the vaccine, but continues to assume a clearly positive benefit–risk ratio due to the rarity of the events and has therefore not decided on any restrictions on the use of the AstraZeneca vaccine [69]. For Germany, the PEI and the STIKO came to a different conclusion and recommend its use, as well as that of the Johnson & Johnson vector vaccine due to similar complications, only for people under 60 years of age after detailed medical information [49].

Comparative data on the efficacy and safety of the vaccines currently used in Germany in patients with IRD is not available. This means that beyond the general differences described and the restrictions on use imposed by the PEI and the STIKO, there is no preference for patients with IRD in favour of a particular vaccine.

For two patient groups with IRD, namely patients in whom rapid complete immunisation is indicated because of urgent therapy with RTX and patients over 60 years of age with confirmed APS (antiphospholipid syndrome) or immunothrombocytopenia, the administration of an mRNA vaccine is recommended as a precautionary measure in view of the DGRh.

The mechanism of the very rare coagulation disorders, thrombopenias, and sinus vein thromboses is probably based on the formation of autoantibodies (VIPI: vaccine-induced prothrombotic immune thrombocytopenia) [66]. The postmarketing surveillance data from Great Britain show comparatively more reported cases of APS and ITP under vaccination with the AstraZeneca vaccine [70] than with the Pfizer/BioNTech vaccine [71], although the number of cases cannot be analysed with statistical certainty. However, details on the cases of VIPI that have occurred so far are hardly available. Among 9 published cases, 2 were patients with pre-existing autoimmune disease, including 1 with positive antiphospholipid antibodies [66]. In a Norwegian study of healthcare workers, antibodies to platelet factor 4 (PF4) were detected in 6/492 cases after vaccination with the AstraZeneca vaccine. None of these cases developed thrombopathy or thrombosis [72].

If this does not delay vaccination, for patients with confirmed APS or immunothrombocytopenia, the use of an mRNA vaccine could represent a risk reduction. This does not apply to cases where only low-titre or single antiphospholipid antibodies are detectable or where there is no chronic immunothrombocytopenia.

With the mRNA vaccines, immunisation can be achieved within about 4–7 weeks: Currently, based on modeling by the RKI and the available data, a vaccination interval of 6 weeks is recommended for the mRNA vaccines, and 12 weeks for the AstraZeneca vaccine [49]. Immunity exists 2 weeks after the second vaccination (BioNTec, Moderna, AstraZeneca) or after the single vaccination (Johnson & Johnson), according to the respective technical information. Patients for whom therapy with RTX is urgent would benefit from rapid immunisation, as a significantly reduced vaccination response can be assumed after such anti‑B cell therapy over a longer period of time. Under ongoing therapy with RTX, e.g. for remission maintenance in AAV, there may only be short time windows in which vaccination appears promising—at least with regard to anti-body formation. In these cases, too, patients would benefit from the use of an mRNA vaccine. There are no concrete data available on this procedure for IRD either. There is only a plausible analogy to other vaccinations.

For both case constellations, the DGRh concludes that vaccination should also be carried out with vector vaccines if, e.g. for reasons of availability, an mRNA vaccine cannot be used promptly, as the risk of a severe SARS-CoV‑2 infection outweighs the possible vaccination risks.

8.10 Vaccinations following SARS-CoV-2 infection

Due to the immunity after a SARS-CoV‑2 infection and because of the continuing vaccine shortage, immunocompromised persons who have undergone a SARS-CoV‑2 infection confirmed by direct pathogen detection (PCR) should, in the opinion of the STIKO, receive a COVID-19 vaccination 6 months after recovery or diagnosis, taking into account prioritisation. Initially, one vaccine dose is sufficient for this, as high antibody concentrations can already be achieved, which cannot be further increased by a second vaccine dose. On the other hand, it must be decided on a case-by-case basis whether a single vaccination is sufficient or whether a complete vaccination series should be administered to persons with “impaired immune function” [49].

8.11 Is the effect of corona vaccination attenuated by antirheumatic therapy/immunosuppressants/-modulants?

Immunomodulatory and immunosuppressive therapies can influence the response to vaccination. Previous studies investigated the antibody response after vaccination against tetanus, influenza, pneumococcus, and varicella in rather small cohorts and focused on the humoral immune reaction. Data on the immune response to vaccinations studied so far (no COVID-19 vaccinations) under different DMARDs are listed in Table 7 (Appendix).

It is uncertain whether the results of these studies can be extrapolated to the SARS-CoV‑2 vaccines and whether there is a difference between the mRNA and vector vaccines. It can also not be assumed that assessment of the humoral immune response alone is sufficient to assess the efficacy of the SARS-CoV‑2 vaccination.

In the meantime, some studies on vaccination against SARS-CoV‑2 have also been able to show that antibody formation depends on the existing immunosuppression. In the first study worldwide using a small cohort of IRD patients, mainly under biologic therapy, the Kiel working group led by B. Hoyer found an immune response in all of them after mRNA vaccination, although the antibody titres against SARS-CoV‑2 were (slightly) reduced compared to healthy controls [61]. Colleagues from Erlangen were then able to show that a certain reduction in the humoral vaccination response can be observed, especially with methotrexate and also with JAK inhibitors [62]. Complete nonresponders were only observed in the Erlangen cohort, the explanation for this is still pending. In both the Kiel and Erlangen studies, it should be noted that the patient cohort was significantly older than the healthy controls and that in the Kiel cohort a large proportion of the differences were no longer statistically significant in an age-matched analysis, which could also be the case for the Erlangen data. This would be supported by the fact that in this study a reduction in the humoral vaccination response was also found in patients without immunosuppression, which would argue for immune senescence as an explanation. The reduction of antibody titres in the Kiel cohort was independent of whether the basic therapy was paused around the vaccinations or not—however, in this cohort, there were neither patients under JAK inhibitors nor under methotrexate.

For RTX, it could be shown in a study with 5 patients [73] and another with 30 patients [74] that antibody formation after COVID-19 vaccination is significantly suppressed depending on the time elapsed since the last administration of RTX. However, an antigen-specific T‑cell response remained mostly present. In the second study, the detection of vaccine antibodies was also dependent on the presence of peripheral B cells in the blood. In another study, positive SARS-CoV‑2 antibody titres were detected in a total of 94% of 404 IRD patients vaccinated with mRNA vaccines. While 100% of patients under TNF inhibitors showed a humoral vaccination response, this was only the case in 26% of patients under rituximab, albeit with an unclear time interval between the last administration and vaccination, and in 73% under mycophenolate [75].

At the end of May 2021, a retrospective study from two cohorts located in New York and Erlangen was published, in which a reduced humoral and cellular response after vaccination with the Pfizer/BioNTech vaccine under methotrexate was reported in some of the vaccinated patients [76]. It remains questionable whether isolated subgroup analyses by age (comparison of those under 55 years of age, as methotrexate patients were 10 years older on average) and by COVID-19 already experienced (8% in the methotrexate group versus 15% in controls and 19% in patients on other therapies) were still statistically adequate. In addition, vaccination response was tested quite shortly after the second vaccination (8–14 days, assuming a vaccination interval of 21 days). So it cannot be ruled out that vaccination response is only delayed. The authors themselves also point out that it is not yet clear what level of immune response is sufficient for a vaccine to be effective. The arbitrarily defined cut-offs do not allow any conclusion as to whether the failure to achieve the desired humoral immune response is also associated with a higher risk of infection. The question of whether ongoing methotrexate therapy in fact weakens the immune response after SARS-CoV‑2 vaccination in a relevant way cannot be answered with certainty based on the available data, and it is even less clear whether this reduces vaccine protection.

8.12 Should immunosuppressive/immunomodulatory therapy be reduced or paused because of vaccination?

Data on temporary pauses of DMARDs at the time of the SARS-CoV‑2 vaccination is limited and refers predominantly to patients with inflammatory joint diseases. Controversy surrounds the study data on methotrexate, which showed an improved humoral immune response with a 2-week break after influenza vaccination. Other data show an increased rate of relapses of IRD with methotrexate paused > 2 weeks, without any further improvement in the immune response. For tofacitinib, it was shown that a 1-week therapy break before and after pneumococcal vaccination did not result in a better immune response. Comparable data on other DMARDs are not available.

For basic considerations of the effectiveness of vaccination, immunosuppression should be as low as possible at the time of vaccination, but not only with regard to vaccinations against SARS-CoV‑2, the risk of reactivation of IRD after a longer pause or discontinuation of immunomodulatory/immunosuppressive therapy is estimated to be higher than the benefit of an even potential improvement of the vaccination response. Therefore, we do not recommend regularly changing an existing immunomodulatory/immunosuppressive therapy because of the vaccination. An exception is the administration of long-acting B‑cell depleting substances (RTX). In this case, consideration should be given to postponing or switching to alternative therapies, taking into account the risk of reactivation of the underlying disease on the one hand and the improvement of a potential vaccine response on the other (see Table 4).

Table 4 Expert consensus on possible adjustments of antirheumatic therapies in the context of vaccinations against COVID-19

Good disease control is also a priority in the context of vaccination against COVID-19. Patients should be informed and involved in the decision-making process if there is even a temporary change in therapy. In order to optimise the vaccination response and in consultation with the treating rheumatologist, a pause of methotrexate, mycophenolate, JAK inhibitors, and abatacept around the COVID-19 vaccination can be considered in the case of well-controlled IRD (Table 4).

8.13 Vaccination sequence

No specific restrictions or changes are seen compared to the time sequences of vaccinations given by the STIKO for patients with IRD. Depending on the urgency of an immunosuppressive therapy that impairs the vaccination response (i.e. especially in the case of planned administration of RTX), the shortest possible intervals between the first and second vaccination should be aimed for, as far as the approval permits, or a single vaccination with a vector vaccine (Johnson & Johnson) (see section 8.9). When administering RTX, a time window of 4 (in urgent cases at least 2) weeks after completion of the COVID-19 vaccination should be observed.

8.14 Can the success of a vaccination against COVID-19 be checked by titre testing?

Under any immunosuppression, the vaccination response may be reduced (see section 8.11). The antibody response after vaccination against COVID-19 can be checked by lab testing of antibody titre. However, routine determination of antibodies against SARS-CoV‑2 is not recommended [77], as it cannot yet be assessed whether these are suitable as surrogate markers for existing immunity, even though there is increasing evidence that neutralising antibodies are predictive of protection against symptomatic infection [78]. With the currently available tests, it is not yet possible to give a precise statement at which antibody level there is actual protection against the disease. Even in the case of a complete absence of antibodies, a cellular immune response against the spike protein could exist and thus a vaccination protection could be present. This is not detected by antibody tests. In the case of low or negative antibodies, it should therefore not be concluded that the vaccination response against COVID-19 has completely failed and that patients are not protected against infection.

Even with a history of infection, routine titre control is not recommended prior to vaccination, as vaccination is recommended regardless of antibody findings.

However, it should be noted that the interpretation of humoral and cellular immunity is a dynamic process and a new assessment of the value of these tests, especially with regard to the evaluation of the need for a booster vaccination in immune suppressed persons with an insufficient vaccination response, may occur quickly. With regard to booster vaccination, a precise assessment will only be possible when criteria for an effective protective effect are defined and controlled studies on booster vaccination (including timing, quantity, active ingredient) are available.

8.15 Other vaccinations

Independent of the considerations on SARS-CoV‑2, other vaccinations should be given according to the recommendations of the STIKO. Data on interactions between these and other known vaccines on the one hand and the SARS-CoV‑2 vaccines on the other are not available. A minimum interval of 14 days before the start and after the end of the vaccination series against SARS-CoV‑2 should be reserved for other vaccinations (with the exception of emergency vaccinations).


  1. 1.

    Schulze-Koops H, Holle J, Moosig F et al (2020) Aktuelle Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie für die Betreuung von Patienten mit rheumatischen Erkrankungen während der SARS-CoV-2/Covid 19-Pandemie. Z Rheumatol 79(4):385–388.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Schulze-Koops H, Specker C, Iking-Konert C, Holle J, Moosig F, Krueger K (2020) Preliminary recommendations of the German Society of Rheumatology (DGRh eV) for the management of patients with inflammatory rheumatic diseases during the SARS-CoV-2/COVID-19 pandemic. Ann Rheum Dis 79(6):840–842.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Schulze-Koops H, Krueger K, Specker C (2020) No advice to discontinue antirheumatic therapy for non-medical reasons in light of SARS-CoV‑2. Response to: “Treatment adherence of patients with sytemic rheumatic diseases in COVID-19 pandemic” by Fragoulis et al. Ann Rheum Dis.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Schulze-Koops H, Iking-Konert C, Leipe J, Hoyer BF, Holle J, Moosig F, Aries P, Burmester G, Fiehn C, Krause A, Lorenz HM, Schneider M, Sewerin P, Voormann A, Wagner U, Krüger K, Specker C, Kommission Pharmakotherapie, Vorstand der Deutschen Gesellschaft für Rheumatologie (2020) Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie e. V. für die Betreuung von Patienten mit entzündlich rheumatischen Erkrankungen im Rahmen der SARS-CoV-2/COVID-19-Pandemie – Update Juli 2020. Z Rheumatol 79(7):679–685.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Schulze-Koops H, Krüger K, Hoyer BF, Leipe J, Iking-Konert C, Specker C, Commission for Pharmacotherapy and the Board of Directors of the German Society for Rheumatology (2021) Updated recommendations of the German Society for Rheumatology for the care of patients with inflammatory rheumatic diseases in times of SARS-CoV-2—methodology, key messages and justifying information. Baillieres Clin Rheumatol.

    Article  Google Scholar 

  6. 6.

    Hasseli R, Mueller-Ladner U, Schmeiser T, Hoyer BF, Krause A, Lorenz HM, Regierer AC, Richter JG, Strangfeld A, Voll RE, Pfeil A, Schulze-Koops H, Specker C (2020) National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV‑2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV‑2 infections in patients with IRD. RMD Open 6(2):e1332.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Leipe J, Hoyer BF, Iking-Konert C, Schulze-Koops H, Specker C, Krüger K (2020) SARS-CoV‑2 & Rheuma : Konsequenzen der SARS-CoV-2-Pandemie für Patienten mit entzündlich rheumatischen Erkrankungen. Ein Vergleich der Handlungsempfehlungen rheumatologischer Fachgesellschaften und Risikobewertung verschiedener antirheumatischer Therapien. Z Rheumatol 79(7):686–691.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Vygen-Bonnet S, Koch J, Bogdan C et al (2021) Beschluss und Wissenschaftliche Begründung der Ständigen Impfkommission (STIKO) für die COVID-19-Impfempfehlung. Epidemiol Bull.

    Article  Google Scholar 

  9. 9.

    Jordan RE, Adab P, Cheng KK (2020) Covid-19: risk factors for severe disease and death. BMJ 368:m1198.

    Article  PubMed  Google Scholar 

  10. 10.

    Gianfrancesco MA, Hyrich KL, Gossec L et al (2020) Rheumatic disease and COVID-19: initial data from the COVID-19 global rheumatology alliance provider registries. Lancet 2(5):e250–e253.

    Article  Google Scholar 

  11. 11.

    Gianfrancesco M, Hyrich KL, Al-Adely S et al (2020) Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis 79(7):859–866.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    RIER investigators group, Pablos JL, Galindo M, Carmona L et al (2020) Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study. Ann Rheum Dis 79(12):1544–1549.

    CAS  Article  Google Scholar 

  13. 13.

    FAI2R/SFR/SNFMI/SOFREMIP/CRI/IMIDIATE consortium and contributors (2020) Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients. Ann Rheum Dis.

    Article  Google Scholar 

  14. 14.

    Hasseli R, Mueller-Ladner U, Hoyer BF, Krause A, Lorenz HM, Pfeil A, Richter J, Schäfer M, Schmeiser T, Strangfeld A, Schulze-Koops H, Voll RE, Specker C, Regierer AC (2021) Older age, comorbidity, glucocorticoid use and disease activity are risk factors for COVID-19 hospitalisation in patients with inflammatory rheumatic and musculoskeletal diseases. RMD Open 7(1):e1464–PMC7823432.

    Article  PubMed  Google Scholar 

  15. 15.

    COVID-19 Global Rheumatology Alliance Consortium, Strangfeld A, Schäfer M, Gianfrancesco MA et al (2021) Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis.

    Article  Google Scholar 

  16. 16.

    Bower H, Frisell T, Di Giuseppe D et al (2021) Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population: a nationwide Swedish cohort study. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  17. 17.

    Rutherford MA, Scott J, Karabayas M, Antonelou M, Gopaluni S, Gray D, Barrett J, Brix SR, Dhaun N, McAdoo SP, Smith RM, Geddes C, Jayne D, Luqmani R, Salama AD, Little M, Basu N, UKIVAS (2021) Risk factors for severe outcomes in patients with systemic vasculitis & COVID-19: a bi-national registry-based cohort study. Arthritis Rheumatol.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Pablos JI, Abasolo I, Alvaro-Gracia JM et al (2021) Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases. Ann Rheum Dis.

    Article  Google Scholar 

  19. 19.

    Freites Nuñez DD, Leon L, Mucientes A et al (2021) Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis.

    Article  Google Scholar 

  20. 20.

    Wang Q, Liu J, Shao R, Han X, Su C, Lu W (2021) Risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population: a systematic review and meta-analysis. Rheumatol Int 41(5):851–861.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Ferri C, Giuggioli D, Raimondo V et al (2020) COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series. Clin Rheumatol 39(11):3195–3204.

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ferri C, Giuggioli D, Raimondo V et al (2021) COVID-19 and systemic sclerosis: clinicopathological implications from Italian nationwide survey study. Lancet Rheumatol 3(3):e166–e168.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Michelena X, Borrell H, López-Corbeto M et al (2020) Incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases treated with targeted biologic and synthetic disease-modifying anti-rheumatic drugs. Semin Arthritis Rheum 50(4):564–570.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Zen M, Fuzzi E, Astorri D et al (2020) SARS-CoV‑2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients. J Autoimmun 112:102502.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Furer V, Rondaan C, Agmon-Levin N et al (2021) Point of view on the vaccination against COVID-19 in patients with autoimmune inflammatory rheumatic diseases. RMD Open 7:e1594.

    Article  PubMed  Google Scholar 

  26. 26.

    Haberman R, Axelrad J, Chen A, Castillo R, Yan D, Izmirly P, Neimann A, Adhikari S, Hudesman D, Scher JU (2020) Covid-19 in immune-mediated inflammatory diseases—case series from New York. N Engl J Med 383(1):85–88.

    Article  PubMed  Google Scholar 

  27. 27.

    Serling-Boyd N, D’Silva KM, Hsu TY, Wallwork R, Fu X, Gravallese EM, Jorge AM, Zhang Y, Choi H, Sparks JA, Wallace ZS (2020) Coronavirus disease 2019 outcomes among patients with rheumatic diseases 6 months into the pandemic. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  28. 28.

    Bachiller-Corral J, Boteanu A, Garcia-Villanueva MJ et al (2021) Risk of severe coronavirus infection (COVID-19) in patients with inflammatory rheumatic diseases. J Rheumatol.

    Article  PubMed  Google Scholar 

  29. 29.

    Cordtz R, Lindhardsen J, Soussi BG, Vela J, Uhrenholt L, Westermann R, Kristensen S, Nielsen H, Torp-Pedersen C, Dreyer L (2020) Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark. Rheumatology.

    Article  PubMed  Google Scholar 

  30. 30.

    Ramirez GA, Gerosa M, Beretta L et al (2020) COVID-19 in systemic lupus erythematosus: data from a survey on 417 patients. Semin Arthritis Rheum 50(5):1150–1157.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Au K, Reed G, Curtis JR, Kremer JM, Greenberg JD, Strand V et al (2011) High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis. Ann Rheum Dis 70:785–791

    Article  Google Scholar 

  32. 32.

    Youssef J, Novosad SA, Winthrop KL (2016) Infection risk and safety of corticosteroid use. Rheum Dis Clin North Am 42(1):157–176, ix–x.

    Article  PubMed  Google Scholar 

  33. 33.

    Favalli EG, Bugatti S, Klersy C, Biggioggero M, Rossi S, De Lucia O, Bobbio-Pallavicini F, Murgo A, Balduzzi S, Caporali R, Montecucco C (2020) Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV‑2 infection in a large cohort of patients with chronic inflammatory arthritis. Arthritis Res Ther 22(1):290.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Schäfer M, Strangfeld A, Hyrich KL et al (2021) Response to: Correspondence on “Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician reported registry” by Mulhearn et al. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  35. 35.

    Schulze-Koops H, Krueger K, Vallbracht I, Hasseli R, Skapenko A (2020) Increased risk for severe COVID-19 in patients with inflammatory rheumatic diseases treated with rituximab. Ann Rheum Dis.

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Leipe J, Wilke EL, Ebert MP, Teufel A, Reindl W (2020) Long, relapsing, and atypical symptomatic course of COVID-19 in a B-cell-depleted patient after rituximab. Semin Arthritis Rheum 50(5):1087–1088.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Avouac J, Airó P, Carlier N et al (2021) Severe COVID-19-associated pneumonia in 3 patients with systemic sclerosis treated with rituximab. Ann Rheum Dis 80:e37

    CAS  Article  Google Scholar 

  38. 38.

    Guilpain P, Le Bihan C, Foulongne V et al (2021) Rituximab for granulomatosis with polyangiitis in the pandemic of covid-19: lessons from a case with severe pneumonia. Ann Rheum Dis 80:e10.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Avouac J, Drumez E, Hachulla E et al (2021) COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study. Lancet Rheumatol.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Sparks J et al (2021) Associations of baseline use of biologic or targeted synthetic DMARDs with COVID 19 severity in rheumatoid arthritis: results from the COVID 19 global rheumatology alliance physician registry. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  41. 41. Accessed: 10. Juni 2021

  42. 42. Accessed: 10. Juni 2021

  43. 43. Accessed: 10. Juni 2021

  44. 44.

    Walsh M, Merkel PA, Peh CA et al (2020) Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med 382(7):622–631.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Stone JH, Tuckwell K, Dimonaco S et al (2017) Trial of tocilizumab in giant-cell arteritis. N Engl J Med 377(4):317–328.

    CAS  Article  PubMed  Google Scholar 

  46. 46. Accessed: 10. Juni 2021

  47. 47.

    Hübner J, Salzberger B, Tenenbaum T Stellungnahme der Deutschen Gesellschaft für Infektiologie (DGI) und der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) zur Wirksamkeit und zum Einsatz der derzeit vorhandenen SARS-CoV-2-Impfstoffe in Deutschland. (Erstellt: 17. Febr. 2021). Accessed: 10. Juni 2021

  48. 48. Accessed: 1. Mai 2021

  49. 49.

    Vygen-Bonnet S, Koch J, Bogdan C et al (2021) Beschluss der STIKO zur 8. Aktualisierung der COVID-19-Impfempfehlung und die dazugehörige wissenschaftliche Begründung. Epidemiol Bull 27:14–31.

    Article  Google Scholar 

  50. 50.

    Polack FP, Thomas SJ, al Kitchin Net (2020) Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 383(27):2603–2615.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Baden LR, El Sahly HM, Essink B et al. For COVE Study Group (2021) Efficacy and safety of the mRNA-1273 SARS-coV‑2 vaccine. N Engl J Med 384(5):403–416.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Specker C, Ad-hoc-Kommission COVID-19 der DGRh, Schulze-Koops H, Vorstand der DGRh (2021) Impfung gegen SARS-CoV‑2 bei entzündlich rheumatischen Erkrankungen: Empfehlungen der DGRh für Ärzte und Patienten. Z Rheumatol 80(1):43–44.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Schulze-Koops H, Specker C, Skapenko A (2021) Vaccination of patients with inflammatory rheumatic diseases against SARS-CoV-2: considerations before widespread availability of the vaccines. RMD Open 7(1):e1553.

    Article  PubMed  Google Scholar 

  54. 54.

    Iking-Konert C, Specker C, Krüger K, Schulze-Koops H, Aries P (2021) Aktueller Stand der Impfung gegen SARS-CoV‑2. Z Rheumatol.

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Curtis JR, Johnson SR, Anthony DD, Arasaratnam RJ, Baden LR, Bass AR, Calabrese C, Gravallese EM, Harpaz R, Kroger A, Sadun RE, Turner AS, Williams AE, Mikuls TR (2021) American college of rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases—version 1. Arthritis Rheumatol.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Arnold J, Winthrop K, Emery P (2021) COVID-19 vaccination and antirheumatic therapy. Rheumatology.

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Shimabukuro TT, Kim SY, Myers TR et al (2021) Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N Engl J Med.

    Article  PubMed  PubMed Central  Google Scholar 

  58. 58. Accessed: 29. Mai 2021

  59. 59.

    Bundesministerium für Gesundheit (2021) Verordnung zum Anspruch auf Schutzimpfung gegen das Coronavirus SARS-CoV‑2 vom 10. März 2021. BAnz AT 11.03.2021 V1

    Google Scholar 

  60. 60.

    Connolly CM, Ruddy JA, Boyarsky BJ, Avery RK, Werbel WA, Segev DL, Garonzik-Wang J, Paik JJ (2021) Safety of the first dose of mRNA SARS-CoV-2 vaccines in patients with rheumatic and musculoskeletal diseases. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  61. 61.

    Geisen UM, Berner DK, Tran F, Sümbül M, Vullriede L, Ciripoi M, Reid HM, Schaffarzyk A, Longardt AC, Franzenburg J, Hoff P, Schirmer JH, Zeuner R, Friedrichs A, Steinbach A, Knies C, Markewitz RD, Morrison PJ, Gerdes S, Schreiber S, Hoyer BF (2021) Immunogenicity and safety of anti-SARS-CoV‑2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  62. 62.

    Simon D, Tascilar K, Fagni F et al (2021) SARS-CoV‑2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  63. 63. Accessed: 15. Mai 2021

  64. 64.

    Grimaldi-Bensouda L, Le Guern V, Kone-Paut I, Aubrun E, Fain O, Ruel M, Machet L, Viallard JF, Magy-Bertrand N, Daugas E, Rossignol M, Abenhaim L, Costedoat-Chalumeau N, PGRx Lupus Study Group. (2014) The risk of systemic lupus erythematosus associated with vaccines: an international case-control study. Arthritis Rheumatol 66(6):1559–1567

    Article  Google Scholar 

  65. 65.

    Westra J, Rondaan C, van Assen S, Bijl M (2015) Vaccination of patients with autoimmune inflammatory rheumatic diseases. Nat Rev Rheumatol 11(3):135–145.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S (2021) Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med.

    Article  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, Goldblatt D, Kotoucek P, Thomas W, Lester W (2021) Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med.

    Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Tiede A, Sachs UJ, Czwalinna A, Werwitzke S, Bikker R, Krauss JK, Donnerstag FG, Weißenborn K, Höglinger GU, Maasoumy B, Wedemeyer H, Ganser A (2021) Prothrombotic immune thrombocytopenia after COVID-19 vaccine. Blood.

    Article  PubMed  PubMed Central  Google Scholar 

  69. 69. Accessed: 13. Mai 2021

  70. 70. Accessed: 13. Mai 2021

  71. 71. Accessed: 13. Mai 2021

  72. 72.

    Sørvoll IH, Horvei KD, Ernstsen SL, Laegreid IJ, Lund S, Grønli RH, Olsen MK, Jacobsen HK, Eriksson A, Halstensen AM, Tjønnfjord E, Ghanima W, Ahlen MT (2021) An observational study to identify the prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in Norwegian health care workers after COVID-19 vaccination. J Thromb Haemost.

    Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Bonelli MM, Mrak D, Perkmann T et al (2021) Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  74. 74.

    Spiera R, Jinich S, Jannat-Khah D (2021) Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  75. 75.

    Ruddy JA, Connolly CM, Boyarsky BJ et al (2021) Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  76. 76.

    Haberman RH, Herati R, Simon D et al (2021) Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease. Ann Rheum Dis.

    Article  PubMed  Google Scholar 

  77. 77. Accessed: 01. Mai 2021

  78. 78.

    Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, Subbarao K, Kent SJ, Triccas JA, Davenport MP (2021) Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV‑2 infection. Nat Med.

    Article  PubMed  Google Scholar 

  79. 79.

    Fischer L, Gerstel PF, Poncet A, Siegrist CA, Laffitte E, Gabay C et al (2015) Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases—A longitudinal study. Arthritis Res Ther 17(1):151

    Article  Google Scholar 

  80. 80.

    Coulson E, Saravanan V, Hamilton J, Long KS, Morgan L, Heycock C et al (2011) Pneumococcal antibody levels after pneumovax in patients with rheumatoid arthritis on methotrexate. Ann Rheum Dis 70(7):1289–1291

    CAS  Article  Google Scholar 

  81. 81.

    Nessib BD, Fazaa A, Miladi S, Sellami M, Ouenniche K, Souabni L et al (2021) Do immunosuppressive agents hamper the vaccination response in patients with rheumatic diseases? A review of the literature. Therapie 76(3):215–219.

    Article  PubMed  Google Scholar 

  82. 82.

    Hua C, Barnetche T, Combe B, Morel J (2014p) Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: A systematic review and meta-analysi. Arthritis Care Res 66:1016–1026

    CAS  Article  Google Scholar 

  83. 83.

    Park JK, Choi Y, Winthrop KL, Song YW, Lee EB (2019) Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: Post hoc analysis of a randomised clinical trial. Ann Rheum Dis 78:1283–1284

    Article  Google Scholar 

  84. 84.

    Kapetanovic MC, Saxne T, Sjöholm A, Truedsson L, Jönsson G, Geborek P (2006) Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Baillieres Clin Rheumatol 45(1):106–111

    CAS  Google Scholar 

  85. 85.

    Park JK, Lee YJ, Shin K, Ha YJ, Lee EY, Song YW et al (2018) Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: A randomised clinical trial. Ann Rheum Dis 77(6):898–904

    CAS  PubMed  Google Scholar 

  86. 86.

    Fomin I, Caspi D, Levy V, Varsano N, Shalev Y, Paran D et al (2006) Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNFα blockers. Ann Rheum Dis 65(2):191–194

    CAS  Article  Google Scholar 

  87. 87.

    Adler S, Krivine A, Weix J, Rozenberg F, Launay O, Huesler J et al (2012) Protective effect of A/H1N1 vaccination in immune-mediated disease—a prospectively controlled vaccination study. Rheumatology 51(4):695–700

    CAS  Article  Google Scholar 

  88. 88.

    Gabay C, Bel M, Combescure C, Ribi C, Meier S, Posfay-Barbe K et al (2011) Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: A prospective, open-label, parallel-cohort, single-center study. Arthritis Rheum 63(6):1486–1496

    CAS  Article  Google Scholar 

  89. 89.

    Keshtkar-Jahromi M, Argani H, Rahnavardi M, Mirchi E, Atabak S, Tara SA et al (2008) Antibody response to influenza immunization in kidney transplant recipients receiving either azathioprine or mycophenolate: A controlled trial. Am J Nephrol 28(4):654–660

    CAS  Article  Google Scholar 

  90. 90.

    Elkayam O, Bashkin A, Mandelboim M, Litinsky I, Comaheshter D, Levartovsky D et al (2010) The effect of infliximab and timing of vaccination on the humoral response to influenza vaccination in patients with rheumatoid arthritis and ankylosing spondylitis. Semin Arthritis Rheum 39(6):442–447

    CAS  Article  Google Scholar 

  91. 91.

    Kivitz AJ, Schechtman J, Texter M, Fichtner A, De Longueville M, Chartash EK (2014) Vaccine responses in patients with rheumatoid arthritis treated with certolizumab pegol: Results from a single-blind randomized phase IV trial. J Rheumatol 41(4):648–657

    CAS  Article  Google Scholar 

  92. 92.

    Richi P, Yuste J, Navío T et al (2021) Impact of biological therapies on the immune response after pneumococcal vaccination in patients with autoimmune inflammatory diseases. Vaccines 9(3):203

    Article  Google Scholar 

  93. 93.

    Mori S, Ueki Y, Hirakata N, Oribe M, Hidaka T, Oishi K (2012) Impact of tocilizumab therapy on antibody response to influenza vaccine in patients with rheumatoid arthritis. Ann Rheum Dis 71(12):2006–2010

    CAS  Article  Google Scholar 

  94. 94.

    Tsuru T, Terao K, Murakami M, Matsutani T, Suzaki M, Amamoto T et al (2014) Immune response to influenza vaccine and pneumococcal polysaccharide vaccine under IL‑6 signal inhibition therapy with tocilizumab. Mod Rheumatol 24(3):511–516

    CAS  Article  Google Scholar 

  95. 95.

    Alten R, Bingham CO, Cohen SB, Curtis JR, Kelly S, Wong D et al (2016) Antibody response to pneumococcal and influenza vaccination in patients with rheumatoid arthritis receiving abatacept. BMC Musculoskelet Disord 17(1):231

    Article  Google Scholar 

  96. 96.

    Ribeiro AC, Laurindo IM, Guedes LK, Saad CG, Moraes JC, Silva CA et al (2013) Abatacept and reduced immune response to pandemic 2009 influenza A/H1N1 vaccination in patients with rheumatoid arthritis. Arthritis Care Res 65(3):476–480

    CAS  Article  Google Scholar 

  97. 97.

    Crnkic Kapetanovic M, Saxne T, Jönsson G, Truedsson L, Geborek P (2013) Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis. Arthritis Res Ther 15(5):R171.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Oren S, Mandelboim M, Braun-Moscovici Y, Paran D, Ablin J, Litinsky I et al (2008) Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response. Ann Rheum Dis 67(7):937–941

    CAS  Article  Google Scholar 

  99. 99.

    Arad U, Tzadok S, Amir S, Mandelboim M, Mendelson E, Wigler I et al (2011) The cellular immune response to influenza vaccination is preserved in rheumatoid arthritis patients treated with rituximab. Vaccine 29(8):1643–1648

    CAS  Article  Google Scholar 

  100. 100.

    Van Assen S, Holvast A, Benne CA, Posthumus MD, Van Leeuwen MA, Voskuyl AE et al (2010) Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum 62(1):75–81

    Article  Google Scholar 

  101. 101.

    Winthrop KL, Silverfield J, Racewicz A, Neal J, Lee EB, Hrycaj P et al (2016) The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis 75(4):687–695

    CAS  Article  Google Scholar 

  102. 102.

    Winthrop KL, Bingham CO, Komocsar WJ, Bradley J, Issa M, Klar R et al (2019) Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: Results from a long-term extension trial substudy. Arthritis Res Ther 21(1):102.

    Article  PubMed  PubMed Central  Google Scholar 

  103. 103.

    Winthrop KL, Wouters AG, Choy EH, Soma K, Hodge JA, Nduaka CI et al (2017) The safety and immunogenicity of live zoster vaccination in patients with rheumatoid arthritis before starting tofacitinib: a randomized phase II trial. Arthritis Rheumatol 69(10):1969–1977

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Christof Specker or Hendrik Schulze-Koops.

Ethics declarations

Conflict of interest

C. Specker, P. Aries, J. Braun, G. Burmester, R. Fischer-Betz, R. Hasseli, J. Holle, B.F. Hoyer, C. Iking-Konert, A. Krause, K. Krüger, M. Krusche, J. Leipe, H.-M. Lorenz, F. Moosig, R. Schmale-Grede, M. Schneider, A. Strangfeld, R. Voll, A. Voormann, U. Wagner and H. Schulze-Koops declare that they have no competing interests.

Ethical standards

For this article no studies with human participants or animals were performed by any of the authors.

The supplement containing this article is not sponsored by industry.

Additional information

All authors are writing on behalf of the Executive Board of the German Society for Rheumatology


Scan QR code & read article online

Supplementary Information



Fig. 1

Cluster-analysis—risk of different pre-existing conditions and age on hospitalisation and mortality in the context of COVID-19 (from [8]). ART arrhythmia or atrial fibrillation; CHF congestive heart failure; CAD coronary artery disease; HTN hypertension; DM diabetes; BMI >30 obesity & overweight; CANC cancer; AST asthma; COPD chronic obstructive pulmonary disease; CKD chronic kidney disease; CLD chronic liver disease; CRB cerebrovascular or stroke; DEM dementia; Auto autoimmune condition; Immun immunodeficiency or immunosuppressed state; Rheuma (inflammatory) rheumatic disease; Organ organ transplant history

Table 5 Various studies on the odds ratio (OR) of IRDs for a severe course, hospitalisation or death in association with COVID-19
Table 6 Common COVID-19 symptoms in patients with inflammatory rheumatic diseases in Germany. Data from the COVID-19 rheumatism registry [6]—with 2729 patients enrolled—(as of 23 May 2021)
Table 7 Studies on vaccination response under prednisone and DMARDs (no COVID-19 vaccinations)

Research agenda

  • Are patients with certain inflammatory rheumatic diseases (IRD) or organ involvement at increased risk of COVID-19 or severe progression?

  • Are certain antirheumatic therapies/therapeutic principles associated with an increased risk of COVID-19 or severe progression?

  • Are glucocorticoids also associated with an increased risk of COVID-19 or a severe course, independent of disease activity?

  • To what extent do other vaccinations (e.g. against influenza, pneumococcus) have a positive effect on the course of COVID-19?

  • Is pausing/discontinuing DMARD therapy before/after COVID-10 vaccination associated with an improved immune response? How long should the pause be for each therapy?

  • What humoral or cellular immunity tests are useful to assess adequate protection against infection after infection or vaccination?

  • What is the significance of SARS-CoV‑2 antibody determinations with regard to protection against newly emerging virus variants?

  • When and at what frequency are booster vaccinations useful?

  • Is it useful to determine peripheral B cells before vaccination?

  • Is there a preference for certain vaccines in the context of rheumatic diseases?

  • How protective are vaccinations in terms of frequency and severity of COVID-19 in IRD?

  • Is the influence of costimulation blockade particularly relevant in the primary response (first vaccination)?

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Specker, C., Aries, P., Braun, J. et al. Updated recommendations of the German Society for Rheumatology for the care of patients with inflammatory rheumatic diseases in the context of the SARS-CoV-2/COVID-19 pandemic, including recommendations for COVID-19 vaccination. Z Rheumatol (2021).

Download citation