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BD and COVID-19 - management advice for clinicians

Suggestions for counselling Behçet’s patients and their families
with questions concerning COVID 19

 

Since March 11, COVID-19 is a pandemic disease. SARS-CoV-2 is the underlying cause of COVID 19. According to a meta-analysis with 46.248 infected patients the most prevalent clinical symptoms of COVID-19 are fever (91 ± 3, 95% CI 86-97%), cough (67 ± 7, 95% CI 59-76%), fatigue (51 ± 0, 95% CI 34-68%) and shortness of breath (30 ± 4, 95% CI 21-40%)1. An estimated 17-30% of patients are asymptomatic2,3.

There is very little evidence on which to base counselling of Behçet’s Disease (BD) patients and their families, but obviously there may be special considerations related either to BD and/or to the immunosuppressive treatment.

We badly need to collect experience with which to develop this site and share information, as these are uncharted waters. Please send us reports, however brief, that we can collate on this website:  e-mail Dorian Haskard at d.haskard@imperial.ac.uk

Disease-independent recommendations are available from WHO4 and ECDC5/CDC6, with further recommendations provided by EULAR7, ERA-EDTA8, the UK and Ireland Vasculitis Society (UKIVAS)9 and specific national societies in the UK10, Germany11´, Austria12 and the Netherlands13.

Here we summarize suggestions for counselling BD patients, with or without immunosuppressive treatment. There may be additional or alternative recommendations from local authorities, depending on the local risk situation.

What follows is for general information only - management responsibility and liability rests with the doctor managing the specific patient.

General aspects

Taking into account the patient’s personal risk factors (eg age, comorbidities, health worker status ± pathogen exposure, long working hours, psychological distress, fatigue, occupational burnout14), degree of community transmission in the area and the individual testing result for SARS-CoV-2, the main aspects of specific counseling are:

1.         To keep social distance with physical distance of at least 6 feet / 2 meters and to stay home when you can. Besides, gatherings with 5-10 people or more should be avoided not only in public, but also privately. Reduce contacts with all non-family members to a minimum.

2.         To limit travelling and contact with hospitals, and to ask for telephone consultations instead of physical visits when no urgent need is present. In particular, patients from areas with few cases should avoid travelling to areas with high transmission and/or countries with less developed health systems.

3.         To keep proper hygiene procedures, frequently hand-cleaning for at least 20 seconds with an alcohol-based hand rub (preferred if hands are not visibly soiled) or soap and water. Hand sanitizers should contain at least 60% alcohol. To avoid touching the face, eyes and nose14.

4.         To regularly clean surfaces in living areas that are touched on a regular basis, using alcohol-based disinfectants15. To the extent possible, touching high-touch surfaces in public places should be avoided, like elevator buttons, door handles, handrails, handshaking with people, etc. One can use tissue or sleeves to cover the hand or finger if something must be touched.

5.         To know about telephone hotlines and how to get medical attention in case of emergency (with the warning signs listed above, especially with pulmonary symptoms). Also everyone should know about local regulations, including (1) self-quarantine in case of suspected close contact with someone tested positive for SARS-CoV-2, (2) isolation in a hospital or at home depending on the severity of the symptoms, and (3) quarantine of sick people as instructed by a physician.

6.         To stop medication only with a physician’s advice and to consider comorbidities as risk factors for COVID-19. The pooled odds ratios of hypertension, respiratory system and cardiovascular disease in severe patients were described as 2.36 (95% CI: 1.46-3.83), 2.46 (95% CI: 1.76-3.44) and 3.42 (95% CI: 1.88-6.22) when compared to non-severe COVID-19 patients, respectively1. If medications are not available, mail-order should be considered for medications.

7.         Regarding the use of a mask  Current advice is only use a mask if taking care of a person with suspected SARS-CoV-2 infection, or if coughing or sneezing17.  However it makes sense for patients on immunosuppressant medication to use a mask if possible, particularly if in hospital or other clinical setting.

Counselling of Behçet’s Disease patients without COVID-19

We do not know if there are increased risks of COVID-19 for patients with immune-mediated diseases like BD disease. The following considerations are based on “first principles” and not yet on any scientific evidence:

(1)    There is no evidence that BD per se increases the susceptibility to viral diseases in general.

(2)    Viral disease may lead to an exacerbation of BD.

(3)     Some or all immunosuppressive drugs may increase the risk of acquisition or the severity of COVID-19.

(4)     There are ongoing discussions about immunosuppressive drugs, including biologics, potentially being beneficial for late complications by preventing the cytokine storm responsible for development of complications such as ARDS, the most feared complication of this virus.  For more information on this issue, see ..https://www.ncbi.nlm.nih.gov/pubmed/32207680

An individual assessment of existing patients’ risk factors is therefore essential for further decisions on starting, adapting, postponing or even stopping immunosuppression.

Principle 1: Any relapse of BD disease has to be avoided if possible, as it may impose a larger risk compared to the effect of immunosuppression. There is no reason to discontinue local treatment, such as for oral ulcers. With respect to oral or injected treatments:

In low-risk situations (areas with few cases, no known community transmission), immunosuppression can be continued. General recommendations should be communicated - as mentioned above.

In middle-risk situations (areas with many cases / risk of community transmission OR high individual risk for example as a health care worker), postponing biologicals (like TNF-inhibitors) maybe appropriate, with longer intervals between applications according to the time since remission and current activity of the disease - depending on a specialist’s decision. Prednisolone may be recommended in dosages from 2.5 or 5 mg daily to 5-10 mg daily to be used in case of a relapse.

In high-risk situations (areas with many cases, risk of community transmission, high individual risk for example as a health care worker), reducing immunosuppressive drugs together with the recommendation of postponing biologicals may be appropriate – depending on a physician’s decision. There is no evidence that such a switch makes a difference, and this is only an opinion-based suggestion.

Principle 2: Telemedicine should be used to replace office visits and to avoid unnecessary travelling to the specialists, long waiting times with other immunosuppressed patients and possible contact with virus-contaminated surfaces, as long as COVID-19 is abundant and restricted measures are taken in individual hospitals. Video or telephone consultations can be offered to the patients. Information can be provided either by trained health care workers, or also, as backup for these health care workers, by physicians. Patients’ travelling can be further reduced by having drugs delivered to their home by relatives or courier services.

Principle 3: Consider to reschedule visits if patients has no treatment side-effects but ongoing remission or low-disease activity, to give the physicians time to inform patients with immunosuppressive drugs over-phone about the virus and to assure that patients adhere to the treatment the specialist considers to be the best (with or without changes).

Management of Behçet’s Disease patients with COVID-19

In case of suspected or proven infection with SARS-CoV-2 especially with fever and/or severe shortness of breath, immunosuppressive drugs should be stopped, and a specialist contacted immediately. Discussion with an infection medicine specialist, and management of the patient according to the local authority’s rules will follow, with hospitalization based on symptoms and risk factors.

Decisions have to be made according to an individual risk-benefit assessment, depending on the precise situation, BD disease activity and the medication used. The following aspects can be considered for specific drugs:

Local treatment (like corticosteroids) can be continued, if applied by the COVID-19 patient.

Colchicine There is no information on positive or negative effects of colchicine on COVID-19, so it is recommended not to stop to prevent a relapse of disease (principle 2).

Oral corticosteroids: double prednisolone dose if <10mg daily due to possibly reduced ability to cope with new body stress (ie adrenal insufficiency), but continue same dose if 10mg daily or higher. Low doses of corticosteroids up to prednisolone 10mg daily can be given in this initial phase, as experience from China indicates that moderate doses of corticosteroids can be beneficial in early stages of the infection without pulmonary abnormalities.

Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs like Azathioprine, Cyclosporin, Methotrexate, Apremilast, …): In case of fever and/ or dyspnea or ARDS: discontinuation is advised, and a specialist to be contacted immediately.

Biological disease-modifying antirheumatic drugs (bDMARDs), like anti-TNF agents: Continuation of a bDMARD depends primarily on whether it is applied for a serious organ-threatening disease. There may be more evidence coming in the future coming on potential positive effects preventing or treating late complications (eg the cytokine storm).

Management of thrombosis risk

Abnormal coagulation parameters, especially markedly elevated D-dimer and fibrinogen degradation products (FDPs), are indicators of poor prognosis in patients with COVID-19 generally (https://www.ncbi.nlm.nih.gov/pubmed/32073213}, and there is some evidence that anticoagulation may improve survival (https://www.ncbi.nlm.nih.gov/pubmed/32220112).

 

 

The International Society on Thrombosis and Haemostasis has issued interim guidance on recognition and management of coagulopathy in COVID-19 @ https://doi.org/10.1111/jth.14810.

 

see also a useful ISTH webinar: 

https://academy.isth.org/isth/2020/covid-19/291581/marcel.levi.26.beverley.jane.hunt.thrombosis.thromboprophylaxis.26.coagulopathy.html?f=menu%3D8%2Abrowseby%3D8%2Asortby%3D2%2Alabel%3D19794

 

 

Useful practical guidance has also come from the German Society for Thrombosis and Hemostasiology @ gth-online.org:

SARS-CoV-2+ patients: Liberal application of LMW-heparins with repeated reevaluations independent from hospitalisation. Thrombopenia and prolonged aPTT or PTT without signs of bleeding are no contraindication for thrombosis prophylaxis

COVID-19+ patients: Testing of D-dimers - with elevated D-dimers (>= 1.5-2.0 mg/l) apply LMW-heparins as prophylaxis against thrombosis and consider hospitalisation independent from severity of COVID-19 symptoms

COVID-19+ patients, hospitalized: apply LMW-heparins as prophylaxis against thrombosis, with controls of hemostatic problems (D-dimer, prothrombin time (Quick/INR), counts of thrombocytes, fibrinogen, antithrombin

COVID-19+ patients, ECMO-treated: use unfractionated heparin to achieve 1.5-1.8-fold prolongation of aPTT

 

In view of the thrombotic risk associated with Behçet’s Disease anyway, particular attention should be given to the early recognition and treatment of coagulopathy in Behçet’s Disease patients with COVID-19.  There is no evidence that Behçet’s Disease should be a specific contraindication to anti-coagulation in this situation.

Future perspectives for treatment of COVID-19

Patients may expect options for new therapeutic approaches. Concerning COVID-19, several approaches are under current investigation and development: (1) vaccination 18;

(2), repurposing of existing drugs like chloroquine/hydroxychloroquine 19 and baricitinib20; A recent commentary in the Lancet has highlighted the importance of a clinical trial of an anti-TNF agent(s) in preventing the cytokine storm in COVID-19 - see https://www.ncbi.nlm.nih.gov/pubmed/32278362

(3) development of new drugs like soluble angiotensin converting enzyme-221,22 or antiviral agents like remdesivir23.

 

References

1.         Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. Epub ahead of print 12 March 2020. DOI: 10.1016/j.ijid.2020.03.017.

2.         Mizumoto K, Kagaya K, Zarebski A, et al. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Eurosurveillance 2020; 25: 2000180.

3.         Nishiura H, Kobayashi T, Suzuki A, et al. Journal Pre-proof Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19). Int J Infect Dis To. Epub ahead of print 2020. DOI: 10.1016/j.ijid.2020.03.020.

4.         WHO | Coronavirus disease 2019, https://www.who.int/emergencies/diseases/novel-coronavirus-2019 (accessed 20 March 2020).

5.         European Centre for Disease Prevention and Control | COVID-19, https://www.ecdc.europa.eu/en (accessed 20 March 2020).

6.         CDC | Coronavirus Disease 2019 (COVID-19), https://www.cdc.gov/coronavirus/2019-nCoV/index.html (accessed 20 March 2020).

7.         EULAR | EULAR Guidance for patients COVID-19 outbreak, https://www.eular.org/eular_guidance_for_patients_covid19_outbreak.cfm (accessed 20 March 2020).

8.         ERA-EDTA: COVID-19 News and Information, https://www.era-edta.org/en/covid-19-news-and-information/ (accessed 20 March 2020).

9.         UK and Ireland Vasculitis Society (UKIVAS) · Statement on COVID-19 for patients with vasculitis, https://ukivas.ndorms.ox.ac.uk/ (accessed 20 March 2020).

10.       British Society for Rheumatology | Covid-19 (Coronavirus), https://www.rheumatology.org.uk/News-Policy/Details/Covid19-Coronavirus-update-members (accessed 25 March 2020).

11.       DgRh: Maßnahmen in Zusammenhang mit den Infektionsrisiken durch COVID-19, https://dgrh.de/Aktuelles/Maßnahmen-in-Zusammenhang-mit-den-Infektionsrisiken-durch-COVID-19.html (accessed 20 March 2020).

12.       ÖGR - Österreichische Gesellschaft für Rheumatologie & Rehabilitation, https://rheumatologie.at/gesellschaft/covid-19/ (accessed 20 March 2020).

13.       Nederlandse Vereiniging voor Rheumatologie: Veel gestelde vragen, https://www.nvr.nl/wp-content/uploads/2020/03/FAQ-1.pdf (accessed 22 March 2020).

14.       WHO: Coronavirus disease (COVID-19) outbreak: Rights, roles and responsibilities of health workers , including key considerations for occupational safety and health, https://www.who.int/docs/default-source/coronaviruse/who-rights-roles-respon-hw-covid-19.pdf?sfvrsn=bcabd401_0 (accessed 19 March 2020).

15.       Kampf G, Todt D, Pfaender S, et al. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. Epub ahead of print 2020. DOI: 10.1016/j.jhin.2020.01.022.

16.       Adhikari SP, Meng S, Wu Y-J, et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Dis Poverty 2020; 9: 29.

17.       Advice on the use of masks in the community, during home care and in healthcare settings in the context of the novel coronavirus (COVID-19) outbreak, https://www.who.int/publications-detail/advice-on-the-use-of-masks-in-the-community-during-home-care-and-in-healthcare-settings-in-the-context-of-the-novel-coronavirus-(2019-ncov)-outbreak (accessed 20 March 2020).

18.       Ahmed SF, Quadeer AA, McKay MR. Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies. Viruses 2020; 12: 254.

19.       Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. Epub ahead of print 10 March 2020. DOI: 10.1016/j.jcrc.2020.03.005.

20.       Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. The Lancet 2020; 395: e30–e31.

21.       Seeking a COVID-19 antidote: the potential of ACE2, https://healthcare-in-europe.com/en/news/seeking-a-covid-19-antidote-the-potential-of-ace2.html (accessed 19 March 2020).

22.       Gurwitz D. Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics. Drug Dev Res 2020; ddr.21656.

23.       Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 269–271.

 


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