To the Editor—More than 1 year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory coronavirus virus 2 (SARS-CoV-2) has infected ∼113 million people and has caused ∼2.5 million deaths, according to the World Health Organization (WHO). Vaccination campaigns have been implemented in several countries worldwide as a prevention strategy for preventing new cases, preventing overcrowding of health facilities and decreasing COVID-19–associated deaths. Nevertheless, the total number of vaccines produced is still not sufficient to address the world population, especially developing countries, and many people continue to be infected daily, requiring hospitalization and health care. 1
Currently, there is no effective treatment for COVID-19. However, some drugs and immunomodulators agents have been suggested to prevent the aggravation of clinical conditions: azithromycin, hydroxychloroquine, remdesivir, lopinavir, ritonavir, dexamethasone, tocilizumab, and others. Reference Magro2 Previous studies have also alluded to the importance of differential diagnosis to facilitate adequate treatment because other infectious lung diseases, such as tuberculosis (TB) and nontuberculous mycobacteria (NTM) pulmonary diseases, may present similar symptoms and result in increased disease severity if they are not correctly identified early. Reference Crisan-Dabija, Grigorescu and Pavel3 Furthermore, TB–COVID-19 and NTM–COVID-19 coinfections have also been described. Reference Crisan-Dabija, Grigorescu and Pavel3,Reference Rodriguez, Bonnano, Khatiwada, Roa, Mayer and Eckardt4 Some medications used in COVID-19 therapy can cause drug–drug interactions with first-line anti-TB drugs, such as antivirals and corticosteroids with rifampicin, Reference Abdullah and Nowalid5,Reference Lemaitre, Solas and Grégoire6 or they can increase the risk of latent TB reactivation and NTM pulmonary diseases, such as antirheumatic and immunomodulatory agents. Reference Brode, Jamieson and Ng7,Reference Kordzadeh-Kermani, Khalili, Karimzadeh and Salehi8 In addition, azithromycin, which has been adopted in the medication management of COVID-19 patients based on its anti-inflammatory and antiviral properties, may result in the development of macrolide-resistant mycobacterial strains (Table 1). Reference Choi, Kim and Lee9
Table 1. Therapeutic Suggested Approaches for COVID-19 and Possible Risk Factors for Mycobacterial Diseases
Note. NTM, non-tuberculous mycobacteria; TB, tuberculosis; RdRp, RNA-dependent RNA polymerase; IL, interleukin; JAK, Janus kinases.
Therefore, when COVID-19 is suspected, differential diagnoses should be performed to prevent risk factors for mycobacterial disease due to inadequate patient treatment. On the other hand, patients with concomitant mycobacterial and COVID-19 etiology require simultaneous treatment, but coadministration of rifampicin with antiviral drugs (eg, remdesivir, lopinavir and ritonavir) should be avoided due to the gastrointestinal and liver toxicity risk in addition to the reduction of antivirals drugs to subtherapeutic concentrations. Reference Lemaitre, Solas and Grégoire6 In a related study, high cortisol levels have been proposed as a possible prognostic marker for COVID-19 associated with adverse outcomes. However, concomitant use of rifampicin with dexamethasone can result in increased dexamethasone metabolism and altered cortisol levels. Reference Abdullah and Nowalid5,Reference Tan, Khoo and Mills10 Under these circumstances, an antimycobacterial protocol should be maintained to reduce the selection of resistant mycobacterial strains, and drug therapy for COVID-19 should be limited to severe cases. Reference Crisan-Dabija, Grigorescu and Pavel3
During the COVID-19 pandemic, TB surveillance programs have also been affected by social isolation and limited patient access to health services, resulting in delayed diagnosis and treatment failure. Moreover, COVID-19 and TB share socioeconomic determinants and comorbidities, so TB–COVID-19 coinfection should be considered, especially in endemic regions, because it can result in potentiated pathogenesis of both diseases and consequent worsening of the patient’s condition. Some measures that may be used in pandemic management to improve TB monitoring include assessing patient and family exposure history and implementing digital health-assistive technologies. Reference Crisan-Dabija, Grigorescu and Pavel3
Due to the absence of specific treatment of COVID-19, only ongoing drug trials have been used to improve the outcomes of hospitalized patients. Nevertheless, drug therapy protocols for COVID-19 can increase susceptibility to mycobacterial infections. Reference Crisan-Dabija, Grigorescu and Pavel3,Reference Rodriguez, Bonnano, Khatiwada, Roa, Mayer and Eckardt4 Thus, further studies analyzing the therapeutic agents used for COVID-19 and their influence on mycobacterial viability and virulence are needed. Their findings will contribute to clinical decision making regarding the best treatment strategy while preventing the development of mycobacterial infections or serious complications in TB–COVID-19 and NTM–COVID-19 coinfections, especially in elderly patients with comorbidities and in TB-endemic countries, such as Brazil and India, which are among the 3 countries with the highest burden of COVID-19 worldwide. 1,Reference Crisan-Dabija, Grigorescu and Pavel3
Acknowledgments
The authors acknowledge support from Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and National Council for Scientific and Technological Development (CNPq).
Financial support
This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES, finance code 001).
Conflicts of interest
All authors report no conflicts of interest relevant to this article.
