Hansen’s disease and COVID-19

by Izabela Feres de Oliveira, Kaicki Teofilo da Silva and Patrícia D. Deps

Hansen’s disease (HD) is a chronic infectious-contagious disease whose main etiological agent is Mycobacterium leprae, an intracellular parasite predominantly affecting the peripheral nerves, skin, mucous surfaces of the upper respiratory tract and eyes. It is transmitted mainly through droplets from the upper respiratory tract or from the mouth during close and prolonged contact with untreated people (1). HD is endemic in Brazil, and between 2014 and 2018 140.578 new cases were identified in the country (2).

The disease named Covid-19 is an acute respiratory syndrome caused by the recently identified Coronavirus, SARS-CoV-2, whose transmission between humans occurs mainly through direct contact with an infected person through exposure to particles or aerosols from respiratory secretions (3). In Brazil, until the beginning of June 2020, there were more than 2.070.000 confirmed cases of Covid-19 (4).

The pathophysiological and immunological interactions between M. leprae and SARS-CoV-2 have not yet been elucidated, but both may share some clinical signs. M. leprae, by invading the nasal mucosa of the individual, can compromise the olfactory bulb in the early stages of the disease, causing olfactory dysfunction and a reduction in the volume of the olfactory bulb, triggering hyposmia or anosmia (5). Anosmia was a clinical sign reported by 45.4% of patients infected with SARS-CoV-2 in a serological survey conducted in Brazil (6). Thus, anosmia, by itself, could lead to confusion in the initial diagnosis of both diseases.

There is little information on the simultaneous infection of these diseases, however the relationship of Covid-19 to reactive HD conditions has been discussed. Hansen’s disease reactions (HDRs) are immunological events affecting a large proportion of persons affected by HD, and a potentially long list of triggers, including infections. HDRs are subdivided into type 1 reactions and type 2 reactions, and the most common is erythema nodosum leprosum (ENL). Covid-19 can trigger severe inflammation, which in theory could increase the risk of the patient developing a type of HDR by the large amount of cytokines involved in the pathogenesis of both clinical conditions, such as TNF-alpha (7). Thus, there is an expectation that persons affected by HD infected with SARS-CoV-2 will develop further episodes of HDR (7).

There is a consensus that multidrug therapy for HD should not be suspended in the case of co-infection. However, case-by-case assessment should be made for the two main drugs used for the treatment of HDRs. Thalidomide is an immunomodulatory drug that inhibits the expression of TNF-α and IFN-γ, affecting pro-inflammatory activity and interfering with the immune response of ENL. In some studies thalidomide when associated with systemic corticosteroids appears to be beneficial in the treatment of pneumonia caused by Covid-19 (7).

Although contradictory, treatment with thalidomide for ENL should not be suspended, with a high risk of sudden exacerbation and development of severe conditions, which require hospitalisation. In this case, increasing the risk of infection of Covid-19, overloading the public health system (8).

Some studies highlight the risk of immunosuppression with systemic corticosteroids used in the treatment of HDRs, correlating them with increased risk of SARS-CoV2 infection (7). The use of a selective phosphodiesterase-4 inhibitor (Apremilast®) associated with low doses of systemic corticosteroids seems promising, which points to a safer way of treating ENL without triggering immunosuppression (9).

The Brazilian Society of Hansen’s Disease (SBH) and the Brazilian Society of Dermatology (SBD) have published conduct guidelines for HD during the Covid-19 pandemic (9,10). SBH advises consideration when using immunosuppressive medications in the course of HD, suggests a risk-benefit assessment, if possible adjusting the dosage of the drugs or even stopping treatment during the reaction outbreak, respecting the individuality of each patient (10).

Information on co-infection in HD and Covid-19 is currently scarce, however, all prevention measures should be maintained so that persons affected by HD do not develop Covid-19. Thus, both medical societies, SBD and SBH, emphasize that multidrug therapy (MDT) used in the treatment of HD should be continued, and that it may be necessary to dispense with sufficient MDT cards for two or three months in order to avoid the risk of patients becoming infected with SARS-CoV2 when they go to the health services (9, 11). In the same context, SBH emphasizes that elective medical appointments should be reduced to the minimum necessary, and when strictly essential, with the use of personal protective equipment, and warns that under no circumstances should the provision of medical care to patients be interrupted (9).

The interim operational guidance for the time of the Covid-19 pandemic is for the maintenance of essential health services, according to the World Health Organization (WHO). It states that prolonged delays in providing interventions may lead to an increase in new infections and relapses, particularly in HD endemic areas. Although there is no official information yet, there is evidence that services aimed at the control of neglected tropical diseases (NTDs), such as HD, have been affected by the pandemic in almost all endemic countries. In the case of HD, it can be said that there has been a reduction in the number of patients seen for clinical assessment, treatment and follow-up, leading to interruptions in the pathways of medical care. WHO also reports delays in the transfer of samples for confirmatory diagnosis of HD, as well as interruptions in the manufacturing and distribution of drugs and supplies for diagnosis of NTD (12).

The WHO recommends that community-based NTDs interventions be delayed, including mass treatment, community surveys, and active case seeking. It recommends that programmes maintain diagnosis and management services for cases such as HD and for complications of other NTDs (10).