To the Editor: The novel coronavirus disease 2019 (COVID-19) has been spreading for more than 5 months since the World Health Organization declared the COVID-19 pandemic in March 2020. As of August 26, the pandemic had resulted in 23 million confirmed cases and 810,000 deaths worldwide. As the likelihood of prolonged spread without sudden termination of this situation increases, the topic of infection risk in patients treated with biologics is becoming crucial in the dermatologic field. Therefore, we conducted a PubMed search for articles reporting biologics exposure and reviewed guidelines on biologics use published during this pandemic. Although according to phase 2 and 3 clinical trials the most frequently experienced adverse effects of biologics include upper respiratory tract infection, nasopharyngitis, or both, no significant increase in the risk of infection has been observed in treated groups compared with control groups.1Lebwohl M. Rivera-Oyola R. Murrell D.F. Should biologics for psoriasis be interrupted in the era of COVID-19?.J Am Acad Dermatol. 2020; 82: 1217-1218Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar,2Wan M.T. Shin D.B. Winthrop K.L. et al.The risk of respiratory tract infections and symptoms in psoriasis patients treated with IL-17-pathway inhibiting biologics: a meta-estimate of pivotal trials relevant to decision-making during the COVID-19 pandemic.J Am Acad Dermatol. 2020; 83: 677-679Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar However, in most clinical studies, data on the incidence of lower respiratory tract infection (main pathogenicity of COVID-19) for each drug are insufficient, probably because of lack of investigator interest and low incidence (less than 5%). The risk of COVID-19 infection in dermatologic patients treated with biologics can be assessed, focusing on areas in which COVID-19 has spread rapidly (Table I). Although the control for biologics-treated groups is the general population rather than patients treated without biologics, the proportion of polymerase chain reaction–confirmed cases in the biologics-treated group is low (approximately 0%-1.8%). Given that the proportion of suspected (not confirmed but symptomatic) cases in the biologics-treated group varies by study, with up to 18% suspected cases being reported,3Carugno A. Gambini D.M. Raponi F. et al.COVID-19 and biologics for psoriasis: a high-epidemic area experience - Bergamo, Lombardy, Italy.J Am Acad Dermatol. 2020; 83: 292-294Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar it is important to distinguish and manage high-risk patients. To properly interpret these data, it is necessary to face the limitations of remarkably low proportions of infected patients in the biologics-treated group, limited adjustment of clinical parameters, and heterogeneity of design between studies.Table ICohort studies for incidence of coronavirus disease 2019 infection in patients treated with biologics for dermatologic disease (listed in sample number)AuthorCountryBiologics-treated groupControl group (general population)PatientsCountAge, yearsSex ratio (M:F)Type of biologics (%)No. of COVID-19–infected patients (%)CountNo. of COVID-19–infected patients (%)Gisondi P et al1Lebwohl M. Rivera-Oyola R. Murrell D.F. Should biologics for psoriasis be interrupted in the era of COVID-19?.J Am Acad Dermatol. 2020; 82: 1217-1218Abstract Full Text Full Text PDF PubMed Scopus (127) Google ScholarItalyPsoriasis520653.2 ± 11.21:0.84Anti–TNF-α antibody (32.2)Anti–IL-12/23 antibody (26.7)Anti–IL-23 antibody (2.7)Anti–IL-17 antibody (38.3)6 (0.12)Damiani G et al2Wan M.T. Shin D.B. Winthrop K.L. et al.The risk of respiratory tract infections and symptoms in psoriasis patients treated with IL-17-pathway inhibiting biologics: a meta-estimate of pivotal trials relevant to decision-making during the COVID-19 pandemic.J Am Acad Dermatol. 2020; 83: 677-679Abstract Full Text Full Text PDF PubMed Scopus (41) Google ScholarItalyPsoriasis1193551:0.47Anti–TNF-α antibody (19.9)Anti–IL-12/23 antibody (45.4)Anti–IL-17 antibody (5.2)22 (1.84)10,060,57454,801 (0.54)Gisondi P et al3Carugno A. Gambini D.M. Raponi F. et al.COVID-19 and biologics for psoriasis: a high-epidemic area experience - Bergamo, Lombardy, Italy.J Am Acad Dermatol. 2020; 83: 292-294Abstract Full Text Full Text PDF PubMed Scopus (34) Google ScholarItalyPsoriasis98056.4 ± 12.41:0.72Anti–TNF-α antibody (50.0)Anti–IL-12/23 antibody (17.0)Anti–IL-23 antibody (0.0)Anti–IL-17 antibody (28.0)0257,3533199 (1.24)Carugno A et al4Pacha O. Sallman M.A. Evans S.E. COVID-19: a case for inhibiting IL-17?.Nat Rev Immunol. 2020; 20: 345-346Crossref PubMed Scopus (194) Google ScholarItalyPsoriasis15951.5 ± 14.01:0.39Anti–TNF-α antibody (33.3)Anti–IL-12/23 antibody or anti–IL-23 antibody (18.9)Anti–IL-17 antibody (47.8)29 (18.24)∗Estimated for patients with suspected COVID-19 (not polymerase chain reaction confirmed). 1. Gisondi P et al. The impact of the COVID-19 pandemic on patients with chronic plaque psoriasis being treated with biological therapy: the Northern Italy experience. Br J Dermatol. 2020;183(2):373-374. 2. Damiani G et al. Biologics increase the risk of SARS-CoV-2 infection and hospitalization, but not ICU admission and death: real-life data from a large cohort during red-zone declaration. Dermatol Ther. 2020;e13475. 3. Gisondi P et al. Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biologic treatment and renal transplant recipients in maintenance immunosuppressive treatment. J Am Acad Dermatol. 2020;83(1):285-287. 4. Carugno A et al. COVID-19 and biologics for psoriasis: a high-epidemic area experience-Bergamo, Lombardy, Italy. J Am Acad Dermatol. 2020;83(1):292-294. 5. Giulia R et al. Experience in patients with hidradenitis suppurativa and COVID-19 symptoms. Dermatol Ther. 2020. https://doi.org/10.1016/j.jaad.2020.06.986. 6. Carungo A et al. No evidence of increased risk for coronavirus disease 2019 (COVID-19) in patients treated with dupilumab for atopic dermatitis in a high-epidemic area - Bergamo, Lombardy, Italy. J Eur Acad Dermatol Venereol. 2020. https://doi.org/10.1111/jdv.16552.Giulia R et al5Toniati P. Piva S. Cattalini M. et al.Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy.Autoimmun Rev. 2020; 19: 102568Crossref PubMed Scopus (578) Google ScholarItalyHidradenitis suppurativa9635NDAnti–TNF-α antibody (47.9)Anti–IL-17 antibody (11.5)0Carungo A et al6ItalyAtopic dermatitis3035.5 ± 11.91:0.5Anti–IL-4/13 antibody (100.0)0COVID-19, Coronavirus disease 2019; F, female patients; IL, interleukin; M, male patients; ND, not described; TNF, tumor necrosis factor.∗ Estimated for patients with suspected COVID-19 (not polymerase chain reaction confirmed). 1. Gisondi P et al. The impact of the COVID-19 pandemic on patients with chronic plaque psoriasis being treated with biological therapy: the Northern Italy experience. Br J Dermatol. 2020;183(2):373-374. 2. Damiani G et al. Biologics increase the risk of SARS-CoV-2 infection and hospitalization, but not ICU admission and death: real-life data from a large cohort during red-zone declaration. Dermatol Ther. 2020;e13475. 3. Gisondi P et al. Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biologic treatment and renal transplant recipients in maintenance immunosuppressive treatment. J Am Acad Dermatol. 2020;83(1):285-287. 4. Carugno A et al. COVID-19 and biologics for psoriasis: a high-epidemic area experience-Bergamo, Lombardy, Italy. J Am Acad Dermatol. 2020;83(1):292-294. 5. Giulia R et al. Experience in patients with hidradenitis suppurativa and COVID-19 symptoms. Dermatol Ther. 2020. https://doi.org/10.1016/j.jaad.2020.06.986. 6. Carungo A et al. No evidence of increased risk for coronavirus disease 2019 (COVID-19) in patients treated with dupilumab for atopic dermatitis in a high-epidemic area - Bergamo, Lombardy, Italy. J Eur Acad Dermatol Venereol. 2020. https://doi.org/10.1111/jdv.16552. Open table in a new tab COVID-19, Coronavirus disease 2019; F, female patients; IL, interleukin; M, male patients; ND, not described; TNF, tumor necrosis factor. Although conventional guidelines prohibit the use of biologics for acute severe infection, the need for recommendation with detailed risk stratification has been raised in preparation for various conditions that fit the current situation. Several expert opinions or consensus statements have been reported recently (Table II). It is generally recommended that asymptomatic low-risk patients continue treatment based on dosing schedule interruption, dysregulated immunogenicity (eg, antidrug antibody), and proven safety, whereas infected patients should discontinue treatment. Furthermore, dermatologists should make sound judgments depending on the circumstances (withholding, down-dosing, or postponement) for patients with exposure history or those at high risk. However, the definitions of high-risk factors vary, and information on restarting treatment for patients who have terminated treatment or initiating treatment for biologics-naive patients is limited.Table IIExpert opinion∗Search of PubMed with following keywords: biologics ("anti–TNF-α antibody," "etanercept," "infliximab," "adalimumab," "certolizumab pegol," "anti–interleukin-12/23 antibody," "anti–interleukin-23 antibody," "ustekinumab," "guselkumab," "tildrakizumab," "risankizumab," "anti–interleukin-17 antibody," "secukinumab," "ixekizumab," "brodalumab," "anti–interleukin-4/13 antibody," "dupilumab," "anti-IgE antibody," "omalizumab," or "biologic") and COVID-19 ("SARS-CoV2," "novel coronavirus infection," or "COVID-19"). Listed in order of publication date. 1. International Psoriasis Council. IPC Statement on the coronavirus (COVID-19) outbreak (accessed 26th Jul 2020, updated Mar 2020). https://www.psoriasiscouncil.org/blog/Statement-on-COVID-19-and-Psoriasis.htm. 2. Price KN et al. COVID-19 and immunomodulator/immunosuppressant use in dermatology. J Am Acad Dermatol. 2020;82(5):e173-e175. 3. American Academy of Dermatology. Recommendations for dermatologists (accessed 26th Jul 2020, updated Apr 2020). https://www.aad.org/member/practice/coronavirus/clinical-guidance/recommendations. 4. Australian Medical Dermatology Group. COVID-19 and the use of immunomodulatory and biologic agents for severe cutaneous disease: an Australian/New Zealand consensus statement. Australas J Dermatol. 2020;61(3):210-216. 5. Brownstone ND et al. Novel coronavirus disease (COVID-19) and biologic therapy in psoriasis: infection risk and patient counseling in uncertain times. Dermatol Ther (Heidelb). 2020;10(3):1-11. 6. Amerio P et al. COVID-19 and psoriasis: should we fear for patients treated with biologics? Dermatol Ther. 2020. https://doi.org/10.1111/dth.13434. 7. Reynolds SD et al. Systemic immunosuppressive therapy for inflammatory skin diseases in children: expert consensus-based guidance for clinical decision-making during the COVID-19 pandemic. Pediatr Dermatol. 2020;37(3):424-434. 8. Conforti C et al. Biologic therapy for psoriasis during the COVID-19 outbreak: the choice is to weigh risks and benefits. Dermatol Ther. 2020. https://doi.org/10.1111/dth.13490. 9. Patruno C et al. Dupilumab and COVID-19: what should we expect? Dermatol Ther. 2020. https://doi.org/10.1111/dth.13502. 10. Sanchez DP et al. Clinical considerations for managing dermatology patients on systemic immunosuppressive or biologic therapy, or both, during the COVID-19 pandemic. J Am Acad Dermatol. 2020;83(1):288-292. 11. Galimberti F et al. Evidenced-based best practice advice for patients treated with systemic immunosuppressants in relation to COVID-19. Clin Dermatol. 2020. https://doi.org/10.1016/j.clindermatol.2020.05.003. 12. Ricardo JW et al. Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during the COVID-19 pandemic. Dermatol Ther. 2020. https://doi.org/10.1111/dth.13687. 13. Karadag AS et al. Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days. Dermatol Ther. 2020. https://doi.org/10.1111/dth.13686. 14. International League of Dermatological Societies. Guidance on the use of systemic therapy for patients with psoriasis/atopic dermatitis during the Covid-19 (Sars-Cov-2, coronavirus) pandemic (accessed 26th Jul 2020, updated May 2020). https://ilds.org/covid-19/guidance-psoriasis-atopic-dermatitis. or official statement for recommendation of biologics use in dermatologic patientsAuthor/organizationSubjects for recommendationCurrent risk of patients for COVID-19 infectionRecommendation for current treatmentInitiation for biologic-naive patientsRemarksInternational Psoriasis Council1Lebwohl M. Rivera-Oyola R. Murrell D.F. Should biologics for psoriasis be interrupted in the era of COVID-19?.J Am Acad Dermatol. 2020; 82: 1217-1218Abstract Full Text Full Text PDF PubMed Scopus (127) Google ScholarTreated for psoriasis with any biologicsCOVID-19 infectedDiscontinuationHigh risk, no CSSDepends on situationHigh risk: >60 y, comorbidities (CVD, DM, hepatitis B, COPD, CKD, cancer)Price KN et al2Wan M.T. Shin D.B. Winthrop K.L. et al.The risk of respiratory tract infections and symptoms in psoriasis patients treated with IL-17-pathway inhibiting biologics: a meta-estimate of pivotal trials relevant to decision-making during the COVID-19 pandemic.J Am Acad Dermatol. 2020; 83: 677-679Abstract Full Text Full Text PDF PubMed Scopus (41) Google ScholarTreated with anti–TNF-α antibodyNo CSS or mild CSSContinuationCSS worsening or high feverDiscontinuationTreated with anti–IL-4/13 antibodyMild to moderate CSSContinuationSevere CSSDiscontinuationTreated with anti–IL-17, anti–IL-12/23, and anti–IL-23 antibodyNo CSS or mild CSSContinuationCSS worsening or high feverDiscontinuationAmerican Academy of Dermatology3Carugno A. Gambini D.M. Raponi F. et al.COVID-19 and biologics for psoriasis: a high-epidemic area experience - Bergamo, Lombardy, Italy.J Am Acad Dermatol. 2020; 83: 292-294Abstract Full Text Full Text PDF PubMed Scopus (34) Google ScholarTreated with any biologicsNo CSSContinuationHigh risk, no CSSDepends on situationPostponement or change to alternative agentHigh risk: >60 y, comorbidities (CVD, DM, severe HTN, liver disease, kidney disease, pulmonary disease, cancer), current smokerCOVID-19 infectedDiscontinuation or postponementAustralian Medical Dermatology Group4Pacha O. Sallman M.A. Evans S.E. COVID-19: a case for inhibiting IL-17?.Nat Rev Immunol. 2020; 20: 345-346Crossref PubMed Scopus (194) Google ScholarTreated with any biologicsNo CSSContinuationDepends on situationHigh risk, no CSSDiscontinuation or dose reductionHigh risk: >60 y, uncontrolled or multiple comorbidities (CVD, CKD, DM, HTN, cancer), high dose or multiple use of other immunosuppressive agent, history of severe/recurrent respiratory tract infectionCSSDiscontinuation or dose reductionCOVID-19 infectedDiscontinuation or postponement (if next injection is scheduled within 31 d)Brownstone ND et al5Toniati P. Piva S. Cattalini M. et al.Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy.Autoimmun Rev. 2020; 19: 102568Crossref PubMed Scopus (578) Google ScholarTreated for psoriasis with any biologicsHigh risk, no CSSDiscontinuation or dose reductionHigh risk: elderly, CVD, HTN, lung disease, DM, cancer, concomitant use of other immunosuppressive agent, immunosuppressive state (HIV), history of infection during biologics treatmentExposure to COVID-19–infected patientDiscontinuation or dose reductionCOVID-19 infectedHolding a doseAmerio P et al6Treated with any biologicsNo CSSContinuationHigh risk and CSSDiscontinuationHigh risk: elderly with comorbidities (HTN, DM, obesity)High risk and exposure to COVID-19–infected patientDiscontinuationHigh risk: elderly with comorbidities (HTN, DM, obesity)Reynolds SD et al7All biologics-treated childrenNo CSSContinuationCSSDepends on situationFor dupilumab, 50% of experts agree to continueHigh risk and exposure to COVID-19–infected patientDiscontinuation or depends on situationFor dupilumab, 50% of experts agree to continueCOVID-19 infectedDiscontinuationFor dupilumab, 16% of experts agree to continueConforti C et al8All biologics treatedCOVID-19 infectedDiscontinuationPatruno C et al9Anti–IL-4/13 antibody treatedNo CSSContinuationSanchez DP et al10All biologics treatedCSSHolding a doseNo CSSContinuationChange to self-injectable agent/home infusion (if possible)Enhancement of self-isolation for patients treated with secukinumab and adalimumabGalimberti F et al11All biologics treatedNo CSSContinuationPostponementCSSDiscontinuationCOVID-19 infectedDiscontinuationRicardo JW et al12Anti–TNF-α antibody treatedCOVID-19 infectedDiscontinuationNo CSSChange to alternative agentAnti–IL-17 antibody treatedNo CSSContinuationCOVID-19 infectedDiscontinuationAnti–IL-12/23 antibody treatedNo CSSContinuationRefrain from changing to anti–IL-23 antibody if possibleCOVID-19 infectedDiscontinuationAnti–IL-23 antibody treatedNo CSSContinuationPossibleCOVID-19 infectedDiscontinuationAnti–IL-4/13 antibody treatedNo CSSContinuationPossibleKaradag AS et al13Anti–IL-12/23 and Anti–IL-23 antibody treatedNo CSSContinuationUse the lowest dose (if possible)International League of Dermatological Societies14All biologics for psoriasis and atopic dermatitis treatedNo CSSContinuationHigh risk, no CSSDepends on situationHigh risk: elderly, comorbidities (DM, COPD, HTN, CKD, liver disease, cancer except for keratinocyte carcinoma)CSSChange to alternative agentPostponementCOVID-19 infectedDiscontinuationCKD, Chronic kidney disease; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; CSS, COVID-19 suspected symptom; CVD, cardiovascular disease; DM, diabetes mellitus; HTN, hypertension; IL, interleukin; TNF, tumor necrosis factor.∗ Search of PubMed with following keywords: biologics ("anti–TNF-α antibody," "etanercept," "infliximab," "adalimumab," "certolizumab pegol," "anti–interleukin-12/23 antibody," "anti–interleukin-23 antibody," "ustekinumab," "guselkumab," "tildrakizumab," "risankizumab," "anti–interleukin-17 antibody," "secukinumab," "ixekizumab," "brodalumab," "anti–interleukin-4/13 antibody," "dupilumab," "anti-IgE antibody," "omalizumab," or "biologic") and COVID-19 ("SARS-CoV2," "novel coronavirus infection," or "COVID-19"). Listed in order of publication date. 1. International Psoriasis Council. IPC Statement on the coronavirus (COVID-19) outbreak (accessed 26th Jul 2020, updated Mar 2020). https://www.psoriasiscouncil.org/blog/Statement-on-COVID-19-and-Psoriasis.htm. 2. Price KN et al. COVID-19 and immunomodulator/immunosuppressant use in dermatology. J Am Acad Dermatol. 2020;82(5):e173-e175. 3. American Academy of Dermatology. Recommendations for dermatologists (accessed 26th Jul 2020, updated Apr 2020). https://www.aad.org/member/practice/coronavirus/clinical-guidance/recommendations. 4. Australian Medical Dermatology Group. COVID-19 and the use of immunomodulatory and biologic agents for severe cutaneous disease: an Australian/New Zealand consensus statement. Australas J Dermatol. 2020;61(3):210-216. 5. Brownstone ND et al. Novel coronavirus disease (COVID-19) and biologic therapy in psoriasis: infection risk and patient counseling in uncertain times. Dermatol Ther (Heidelb). 2020;10(3):1-11. 6. Amerio P et al. COVID-19 and psoriasis: should we fear for patients treated with biologics? Dermatol Ther. 2020. https://doi.org/10.1111/dth.13434. 7. Reynolds SD et al. Systemic immunosuppressive therapy for inflammatory skin diseases in children: expert consensus-based guidance for clinical decision-making during the COVID-19 pandemic. Pediatr Dermatol. 2020;37(3):424-434. 8. Conforti C et al. Biologic therapy for psoriasis during the COVID-19 outbreak: the choice is to weigh risks and benefits. Dermatol Ther. 2020. https://doi.org/10.1111/dth.13490. 9. Patruno C et al. Dupilumab and COVID-19: what should we expect? Dermatol Ther. 2020. https://doi.org/10.1111/dth.13502. 10. Sanchez DP et al. Clinical considerations for managing dermatology patients on systemic immunosuppressive or biologic therapy, or both, during the COVID-19 pandemic. J Am Acad Dermatol. 2020;83(1):288-292. 11. Galimberti F et al. Evidenced-based best practice advice for patients treated with systemic immunosuppressants in relation to COVID-19. Clin Dermatol. 2020. https://doi.org/10.1016/j.clindermatol.2020.05.003. 12. Ricardo JW et al. Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during the COVID-19 pandemic. Dermatol Ther. 2020. https://doi.org/10.1111/dth.13687. 13. Karadag AS et al. Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days. Dermatol Ther. 2020. https://doi.org/10.1111/dth.13686. 14. International League of Dermatological Societies. Guidance on the use of systemic therapy for patients with psoriasis/atopic dermatitis during the Covid-19 (Sars-Cov-2, coronavirus) pandemic (accessed 26th Jul 2020, updated May 2020). https://ilds.org/covid-19/guidance-psoriasis-atopic-dermatitis. Open table in a new tab CKD, Chronic kidney disease; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; CSS, COVID-19 suspected symptom; CVD, cardiovascular disease; DM, diabetes mellitus; HTN, hypertension; IL, interleukin; TNF, tumor necrosis factor. In conclusion, with advances in the understanding of COVID-19 pathogenesis and opposing suggestions of certain biologics as an alternative treatment option for COVID-19 disease,4Pacha O. Sallman M.A. Evans S.E. COVID-19: a case for inhibiting IL-17?.Nat Rev Immunol. 2020; 20: 345-346Crossref PubMed Scopus (194) Google Scholar,5Toniati P. Piva S. Cattalini M. et al.Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy.Autoimmun Rev. 2020; 19: 102568Crossref PubMed Scopus (578) Google Scholar it will be necessary for guidelines about biologics use to be consistently modified and integrated at the pannational level in the COVID-19 era. Moreover, the guidelines need to be tailored to each condition, considering the differences in the prevalence of COVID-19, the incidence of pulmonary complications, quarantine policy, and insurance coverage of biologics between countries.