key: cord-0948826-y0ar276h authors: Rodrigues, Ana Carolina; Adamoski, Douglas; Genelhould, Gustavo; Zhen, Felipe; Yamaguto, Guilherme Eiji; Araujo‐Souza, Patrícia Savio; Nogueira, Meri Bordignon; Raboni, Sonia Mara; Bonatto, Ana Claudia; Gradia, Daniela Fiori; Carvalho de Oliveira, Jaqueline title: NEAT1 and MALAT1 are highly expressed in saliva and nasopharyngeal swab samples of COVID‐19 patients date: 2021-09-08 journal: Mol Oral Microbiol DOI: 10.1111/omi.12351 sha: 3e4467a802dbb5d1972ed5655b285dc8153bff4e doc_id: 948826 cord_uid: y0ar276h COVID‐19, caused by the SARS‐CoV‐2 virus, has become a significant global public health problem, with a wide variety of clinical manifestations and disease progression outcomes. LncRNAs are key regulators of the immune response and have been associated with COVID‐19 risk infection. Previous studies focused mainly on in‐silico analysis of lncRNA expression in the lungs or peripheral blood cells. We evaluated the expression of lncRNAs NEAT1, MALAT1, and MIR3142 in saliva and nasopharyngeal swab from SARS‐CoV‐2 positive (n = 34) and negative patients (n = 46). A higher expression of the lncRNAs NEAT1 and MALAT1 (p < 0.05) were found in positive samples. NEAT1 had a higher expression mainly in saliva samples (p < 0.001), and MALAT1 was upregulated in nasopharyngeal samples (p < 0.05). Area under the ROC curve for NEAT1 in saliva was 0.8067. This study was the first to investigate the expression of lncRNAs in saliva and nasopharyngeal samples of COVID‐19 patients, which gives new insights into the initial response to infection and infectivity and may provide new biomarkers for severity and targets for therapy. LncRNAs (long noncoding RNAs) are transcripts larger than 200 nucleotides in length that do not appear to have protein-coding potential (Cabili et al., 2011) , although some of them may produce small functional peptides (Choi et al., 2019) . Further to complex regulation in multiple cell processes, lncRNAs are emerging as critical regulators of immune responses (Bocchetti et al., 2021; Heward & Lindsay, 2014) , and some may control innate and adaptive cell types (Chen et al., 2017) . Antiviral immune responses are also influenced by lncRNAs Ouyang et al., 2016; Qiu et al., 2018) , but information regarding a role in COVID-19 patients is limited. In summary, this study observed a differential expression of NEAT1 and MALAT1 lncRNAs comparing infected and noninfected individuals with SARS-CoV-2 in saliva or NPS samples. For NEAT1, this difference was observed mainly in saliva samples. In contrast, MALAT1 high expression was prominent in positive nasopharyngeal samples. Both lncRNAs have been associated with immune system responses. NEAT1 is an inflammatory regulator that promotes activation of inflammasomes in macrophages (Zhang et al., 2019) and induces inflammatory cytokines such as interleukin-6 (IL-6) and CXCL8 (Tang et al., 2020) . IL-6 and the NLRP3 inflammasome are primary immune components in responses to SARS-CoV-2 infection (Paniri & Akhavan-Niaki, 2020) . MALAT1 also exerts various immunological effects including the mediation of NLRP3 inflammasome activation (Menon & Hua, 2020; Yu et al., 2018) . Through NF-κB and HIF-1α activation, MALAT1 increases production of inflammatory cytokines, such as IL-6 and TNF-α, to promote inflammatory cell infiltration and tissue damage (Tian et al., 2018) . Furthermore, MALAT1 has been linked to M1like activity in macrophages, promoting pulmonary inflammation and injury (Cui et al., 2019) . increased NEAT1 expression was found in severe COVID-19 patients compared to moderate patients and healthy individuals (Tang et al., 2020) . Also, by a single-cell transcriptomic analysis in the respiratory tract and peripheral blood, NEAT1 and MALAT1 were differentially expressed between mild and severe patients (Huang et al., 2021) . SARS-CoV-2′s first entry is through mouth and nose cells, and differential expression in these sites may be associated with an initial response to infection, infectivity, viral dosage, and clinical association. The authors have stated explicitly that there are no conflicts of interest in connection with this article. The peer review history for this article is available at https://publons. com/publon/10.1111/omi.12351 The data that support the findings of this study are available from the corresponding author upon request. Adamoski https://orcid.org/0000-0001-5062-2586 Meri Bordignon Nogueira https://orcid.org/0000-0001-6221-2891 Jaqueline Carvalho de Oliveira https://orcid.org/0000-0002-5314-3107 Large-scale screening of asymptomatic for SARS-CoV-2 variants of concern and rapid P.1 takeover LncRNAs and immunity: Coding the immune system with noncoding oligonucleotides Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses Gene regulation in the immune system by long noncoding RNAs The small peptide world in long noncoding RNAs Long noncoding RNA Malat1 regulates differential activation of macrophages and response to lung injury Long non-coding RNAs in the regulation of the immune response LncRNAs NEAT1 and MALAT1 differentiate inflammation in severe COVID-19 patients LncRNA Malat1 inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity The long non-coding RNAs: Paramount regulators of the NLRP3 inflammasome LncRNAs regulate the innate immune response to viral infection Emerging role of IL-6 and NLRP3 inflammasome as potential therapeutic targets to combat COVID-19: Role of lncRNAs in cytokine storm modulation Long non-coding RNAs: Regulators of viral infection and the interferon antiviral response The noncoding and coding transcriptional landscape of the peripheral immune response in patients with COVID-19 The long noncoding RNA MALAT1 is increased in renal ischemia-reperfusion injury and inhibits hypoxia-induced inflammation Protein coding and long noncoding RNA (lncRNA) transcriptional landscape in SARS-CoV-2 infected bronchial epithelial cells a role for interferon and inflammatory response LncRNA MALAT1 sponges miR-133 to promote NLRP3 inflammasome expression in ischemiareperfusion injured heart NEAT1 and MALAT1 are highly expressed in saliva and nasopharyngeal swab samples of COVID-19 patients