Long-Term Evolution of SARS-CoV-2 in an Immunocompromised Patient with Non-Hodgkin Lymphoma.

Recent studies have shown that persistent SARS-CoV-2 infections in immunocompromised patients can trigger the accumulation of an unusual high number of mutations with potential relevance at both biological and epidemiological levels. Here, we report a case of an immunocompromised patient (non-Hodgkin lymphoma patient under immunosuppressive therapy) with a persistent SARS-CoV-2 infection (marked by intermittent positivity) over at least 6 months. Viral genome sequencing was performed at days 1, 164, and 171 to evaluate SARS-CoV-2 evolution. Among the 15 single-nucleotide polymorphisms (SNPs) (11 leading to amino acid alterations) and 3 deletions accumulated during this long-term infection, four amino acid changes (V3G, S50L, N87S, and A222V) and two deletions (18-30del and 141-144del) occurred in the virus Spike protein. Although no convalescent plasma therapy was administered, some of the detected mutations have been independently reported in other chronically infected individuals, which supports a scenario of convergent adaptive evolution. This study shows that it is of the utmost relevance to monitor the SARS-CoV-2 evolution in immunocompromised individuals, not only to identify novel potentially adaptive mutations, but also to mitigate the risk of introducing "hyper-evolved" variants in the community. IMPORTANCE Tracking the within-patient evolution of SARS-CoV-2 is key to understanding how this pandemic virus shapes its genome toward immune evasion and survival. In the present study, by monitoring a long-term COVID-19 immunocompromised patient, we observed the concurrent emergence of mutations potentially associated with immune evasion and/or enhanced transmission, mostly targeting the SARS-CoV-2 key host-interacting protein and antigen. These findings show that the frequent oscillation in the immune status in immunocompromised individuals can trigger an accelerated virus evolution, thus consolidating this study model as an accelerated pathway to better understand SARS-CoV-2 adaptive traits and anticipate the emergence of variants of concern.

[Multidrug-Resistant Tuberculosis by Strains of Beijing Family, in Patients from Lisbon, Portugal: Preliminary Report]. / Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo Preliminar.

INTRODUCTION: Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known. MATERIAL AND METHODS: Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains. RESULTS: Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients). DISCUSSION: Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa. CONCLUSION: Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

Introdução: As estirpes de Mycobacterium tuberculosis da família Beijing estão associadas à multirresistência. As estirpes da família Lisboa prevalecem entre os doentes com tuberculose multirresistente e extensivamente resistente desta região, mas vários estudos documentam  a presença da família Beijing, embora desconhecendo-se as características dos doentes donde foram isoladas. Material e Métodos: Estudo retrospectivo de 104 estirpes multirresistentes e extensivamente resistentes de Mycobacterium tuberculosis, isoladas e genotipadas, de 1993 a 2015, de igual número de doentes de Lisboa. Avaliámos a prevalência de ambas as famílias de estirpes e as características epidemiológicas e clínicas, dos infectados por estirpes Beijing. Resultados: Setenta e quatro estirpes (71,2%) pertenciam à família Lisboa, 25 (24,0%) apresentavam padrão genotípico único e cinco (4,8%) pertenciam à família Beijing, estas identificadas depois de 2009. Os infectados pela estirpe Beijing eram de nacionalidade angolana (n = 1), ucraniana (n = 2) e portuguesa (n = 2), na maioria jovens, quatro em cinco imunocompetentes e sem história de tuberculose anterior. Todos tinham tuberculose multirresistente. Não detectámos apresentações clínicas ou radiológicas diferenciadoras, nem padrão de resistências predominante. A taxa de cura foi alta (quatro doentes). Discussão: Apesar do número de doentes infectados pela estirpe Beijing ser reduzido, sugere proporção importante de tuberculose primária, potencial de transmissão na comunidade, mas, também, melhor evolução clínica do que a descrita para outras estirpes, como a W-Beijing ou a Lisboa. Conclusão: Apesar das estirpes da família Lisboa serem as principais responsáveis pelos casos de tuberculose multirresistente e extensivamente resistente na região de Lisboa, as estirpes Beijing transmitem-se na cidade e poderão modificar as características locais da epidemia.