Coronavirus persistence in human respiratory tract and cell culture: An overview

Gaspar-Rodríguez, Adriana; Padilla-González, Ana; Rivera-Toledo, Evelyn

doi:10.1016/j.bjid.2021.101632

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Review Article • Braz. j. infect. dis 25 (05) • 2021 • https://doi.org/10.1016/j.bjid.2021.101632 copy

Coronavirus persistence in human respiratory tract and cell culture: An overview

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Emerging human coronaviruses, including the recently identified SARS-CoV-2, are relevant respiratory pathogens due to their potential to cause epidemics with high case fatality rates, although endemic coronaviruses are also important for immunocompromised patients. Long-term coronavirus infections had been described mainly in experimental models, but it is currently evident that SARS-CoV-2 genomic-RNA can persist for many weeks in the respiratory tract of some individuals clinically recovered from coronavirus infectious disease-19 (COVID-19), despite a lack of isolation of infectious virus. It is still not clear whether persistence of such viral RNA may be pathogenic for the host and related to long-term sequelae.

In this review, we summarize evidence of SARS-CoV-2 RNA persistence in respiratory samples besides results obtained from cell culture and histopathology describing long-term coronavirus infection. We also comment on potential mechanisms of coronavirus persistence and relevance for pathogenesis.

Keywords:
SARS-CoV-2; Persistence of viral RNA; Viral pathogenesis; Non-productive infection; Cell culture

Patient/age (Year old)	Clinical condition	RT-PCR positivity	Replicative-competent SARS-CoV-2 isolation	Commentaries	References
Female/71	Chronic lymphocytic leukemia, acquired hypo-gammaglobulinemia	105 days	On days 49 and 70 post-symptom onset	Symptoms were not developed along viral infection. Viral load was controlled after day 70 by convalescent plasma	³⁹39 Avanzato VA, Matson MJ, Seifert SN, et al. Case study: prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised individual with cancer. Cell. 2020;183:1901-1912.e9.
Male/61	Liver transplant, immunosuppressive therapy for 11 years	52 days	-	Mild symptoms and lung damage. Transient suspension of immunosuppressive drugs and treatment with lopinavir/ritonavir	⁴⁰40 Wei L, Liu B, Zhao Y, Chen Z. Prolonged shedding of SARSCoV-2 in an elderly liver transplant patient infected by COVID19: a case report. Ann Palliat Med. 2020. apm-20-996.
Male/62	Heart transplant, immunosuppressive regimen	35 days	On days18 and 21 post-symptom onset	Mild symptoms. Immunosuppressive therapy was maintained. Hydroxychloroquine was administered from day 7-14 up to end of symptoms	⁴¹41 Decker A, Welzel M, Laubner K, et al. Prolonged SARS-CoV-2 shedding and mild course of COVID-19 in a patient after recent heart transplantation. Am J Transplant. 2020;20:3239- 45.
Female/9 months old	Myelomonocytic leukemia with stem cell transplant	At least 4 months	-	Symptoms and lung damage were developed after 45 days from first positive SARS-CoV-2 RT-PCR. Convalescent plasma improved lung lesions	⁴²42 Balashov D, Trakhtman P, Livshits A, et al. SARS-CoV-2 convalescent plasma therapy in pediatric patient after hematopoietic stem cell transplantation. Transfus Apher Sci. 2021;60:102983.
Male/47	Follicular lymphoma in remission. Immunocompromised status.	55-59 days	On day 59 after first positive test	Mild symptoms and lung damage. RT-PCR negativization on day 65	⁴³43 Nakajima Y, Ogai A, Furukawa K, et al. Prolonged viral shedding of SARS-CoV-2 in an immunocompromised patient. J Infect Chemother. 2021;27:387-9.
Male/49	Mixed connective tissue disease, rheumatoid arthritis, and systemic lupus. Immunosuppressive therapy and acquired humoral deficiency	60 days	-	Development of respiratory distress after a week from first RT-PCR positive test.Treatment with IVIG, hydroxychloroquine and azithromycin	⁴⁴44 Schend J, Daniels P, Sanan N, Tcheurekdjian H, Hostoffer R. Clinical observation of COVID-19 in a patient with an acquired humoral deficiency secondary to chemotherapeutic agents. Allergy Rhinol (Providence). 2020;11:2152656720978764.
Female/63	No Hodgkin lymphoma in remission. Treatment with anti-CD20 MAb was suspended 37 days previous to symptoms onset	At least 74 days	-	Undetectable IgG on day 75 post-symptom onset. Hospitalization on day 88 and treatment with convalescent plasma that resolved symptoms	⁴⁵45 Moore JL, Ganapathiraju PV, Kurtz CP, Wainscoat B. A 63-year-old woman with a history of non-hodgkin lymphoma with persistent SARS-CoV-2 infection who was seronegative and treated with convalescent plasma. Am J Case Rep. 2020;21:e927812.
Male/60	Mantle cell lymphoma. Treatment with anti-CD20, prednisone, cyclophosphamide and doxorubicin	156 days	Along 119 days	Genome sequencing of nine viral isolates, suggested within-host evolution and no reinfection	⁴⁶46 Baang JH, Smith C, Mirabelli C, et al. Prolonged severe acute respiratory syndrome coronavirus 2 replication in an immunocompromised patient. J Infect Dis. 2021;223:23-7.
Female/78	Type 2 diabetes and hypertension. Complications of thyroidectomy 23 years ago that required tracheostomy	At least 47 days	-	Supplemental oxygen was required. Discharge on day 55 post-symptom onset	⁴⁷47 McKie AM, Jones TPW, Sykes C. Prolonged viral shedding in an immunocompetent patient with COVID-19. BMJ Case Rep. 2020;13:e237357.
Male/45	Antiphospholipid syndrome complicated by diffuse alveolar hemorrhage. Anticoagulation therapy and glucocorticoids	151 days	-	Initially, patient developed fever. Complications avoid COVID-19 resolution. Analysis of postmortem tissue revealed high viral loads in lungs and spleen. Viral genome sequencing was consistent with persistent infection	⁴⁸48 Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med. 2020;383:2291-3.

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[1] * Corresponding author at: Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autonoma de M exico, Ciudad Universitaria, Coyoac an, 04510, Mexico City, Mexico. E-mail addresses: anipadillag@ciencias.unam.mx (A. Padilla-Gonzalez), evelyn.rivera@unam.mx (E. Rivera-Toledo).