SARS-CoV-2 Viral Load, IFNλ Polymorphisms and the Course of COVID-19: An Observational Study

Amodio, Emanuele; Pipitone, Rosaria Maria; Grimaudo, Stefania; Immordino, Palmira; Maida, Carmelo Massimo; Prestileo, Tullio; Restivo, Vincenzo; Tramuto, Fabio; Vitale, Francesco; Craxı̀, Antonio; Casuccio, Alessandra

doi:10.3390/jcm9103315

Cited by 35 publications

(38 citation statements)

References 27 publications

(27 reference statements)

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“…This observation may help to understand the disproportionate prevalence of COVID-19 in the black population with a lower frequency of the protective CC allele than in the white population (6,9). The fact that there were no significant differences in CC expression between non-severe and severe disease proposes a role for IFNL4 in early stages, but not in disease progression as previously suggested (10).…”

Section: Discussionsupporting

confidence: 55%

IFNL4 genetic variant can predispose to COVID-19

Jmr

Rivas

Jfs

et al. 2021

Preprint

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COVID-19 currently represents a major public health problem. The causes that underlying susceptibility to infection in have not yet been determined. Interferons (IFNs) are intensively being investigated because of their antiviral properties. Among them, Interferon lambda 4 (IFNL4) has been reported to have antiviral activity against viral infections of the upper respiratory tract, Hepatitis virus C (HCV), and coronaviruses. The importance of this cytokine was shown by the fact that genetic variants of IFNL4 have been associated with viral clearance and response to IFNs-based therapies in HCV and other infections by RNA virus. In this study, we have investigated whether the rs12979860 polymorphism within the IFNL4 was also associated with COVID-19. Our findings show that the presence of the CC allele of rs12979860 was significantly lower in SARS-CoV-2 infected patients with regard to non-COVID-19 controls (38% vs 55%, p<0001). These results were not affected by sex, age, and severity of disease. These findings suggest that the CC allele may also confer protection against COVID-19. They may contribute to understanding the mechanisms of disease, the response to IFN-based treatments, and the racial differences observed in the disease.

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Section: Discussionsupporting

confidence: 55%

IFNL4 genetic variant can predispose to COVID-19

Jmr

Rivas

Jfs

et al. 2021

Preprint

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“…Amodio et al . demonstrated that the median PCR Ct was significantly lower in patients who died or needed critical care than in those who were hospitalized and discharged alive, or exclusively attended at home, but after adjusting for age and sex, there was not and independent association with critical care need or death 13 .…”

Section: Discussionmentioning

confidence: 92%

“…Some studies have reported that a high number of virus copies in NP swabs, mainly defined as a cycle threshold (Ct) < 25 or < 22 in the real-time polymerase chain reaction (RT-PCR), was an independent risk factor for intubation and/or death 8 – 11 . However, other studies have not found independent association between low Ct values and critical care admission or death 12 , 13 . In short, the real impact of initial SARS-CoV-2 viral load in NP swabs on COVID-19 patients’ outcomes is not been fully elucidated, and this issue remains controversial 14 .…”

Section: Introductionmentioning

confidence: 85%

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

Salto‐Alejandre

Berastegui‐Cabrera

Camacho‐Martínez

et al. 2021

Sci Rep

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The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.

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“…2020 [ 118 ] CCR5 3p21.31 Chemokine receptor CCR5 Δ32 Increased susceptibility to SARS-CoV-2 infection and mortality Panda. 2020 [ 74 ] IFNL4 19q13.2 Immune response to viral infection rs368234815TT/∆G Higher viral loads Amodio et al 2020 [ 79 ] Other genes DBP 4q11–q13 Regulator of total and free vitamin D metabolite levels rs7041 GT and TT genotype are positively and negatively related to the rate of SARS-CoV-2 infection and mortality, respectively Karcioglu et al 2020 [ 141 ] DPP4 2q24.2. Serine exopeptidase rs13015258 Expression of key regulatory genes related to internalization of SARS-CoV-2 into the cell Senapati et al 2020 [ 62 ] VKORC1 16p11.2 Decreased vitamin K level 1639A (rs9923231) Associated with protection against thrombotic complications of COVID-19 Janssen et al 2020 [ 217 ] …”

Section: Angiotensin-converting Enzyme 1 and Angiotensin-converting Enzyme 2 Polymorphismsmentioning

confidence: 99%

“…IFNL4 is located on chromosome 19q13.2 and is involved in the defense against viral infections, such as HCV, RSV and influenza virus [ 78 ]. Amodio et al reported that polymorphisms at the rs368234815TT/∆G locus of the IFNL4 gene are associated with a higher SARS-CoV-2 viral load [ 79 ].…”

Section: Immune System Gene Polymorphismmentioning

confidence: 99%

Human gene polymorphisms and their possible impact on the clinical outcome of SARS-CoV-2 infection

et al. 2021

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The SARS-CoV-2 pandemic has become one of the most serious health concerns globally. Although multiple vaccines have recently been approved for the prevention of coronavirus disease 2019 (COVID-19), an effective treatment is still lacking. Our knowledge of the pathogenicity of this virus is still incomplete. Studies have revealed that viral factors such as the viral load, duration of exposure to the virus, and viral mutations are important variables in COVID-19 outcome. Furthermore, host factors, including age, health condition, co-morbidities, and genetic background, might also be involved in clinical manifestations and infection outcome. This review focuses on the importance of variations in the host genetic background and pathogenesis of SARS-CoV-2. We will discuss the significance of polymorphisms in the ACE-2, TMPRSS2, vitamin D receptor, vitamin D binding protein, CD147, glucose‐regulated protein 78 kDa, dipeptidyl peptidase-4 (DPP4), neuropilin-1, heme oxygenase, apolipoprotein L1, vitamin K epoxide reductase complex 1 (VKORC1), and immune system genes for the clinical outcome of COVID-19.

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SARS-CoV-2 Viral Load, IFNλ Polymorphisms and the Course of COVID-19: An Observational Study

Cited by 35 publications

References 27 publications

IFNL4 genetic variant can predispose to COVID-19

IFNL4 genetic variant can predispose to COVID-19

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

Human gene polymorphisms and their possible impact on the clinical outcome of SARS-CoV-2 infection

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