Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak

LoTempio, Jonathan; Billings, Erik; Draper, Kyah; Ralph, Christal; Moshgriz, Madhi; Duong, Nhat; Bard, Jennifer Dien; Gai, Xiaowu; Wessel, David; DeBiasi, Roberta L.; Campos, Joseph M.; Vilain, Éric; Delaney, Meghan; Michael, Drew G

doi:10.1101/2021.02.08.21251344

Cited by 6 publications

(7 citation statements)

References 30 publications

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“…Children are less likely than adults to have severe disease when infected with SARS-CoV-2 despite having viral loads as high as adults (Charles Bailey et al, 2020;Heald-Sargent et al, 2020;Li et al, 2020;LoTempio et al, 2021;Lu et al, 2020;Poline et al, 2020;Yonker et al, 2020). Rarely, after SARS-CoV-2 clearance from the upper airways, children can develop severe Multisystem Inflammatory Syndrome in Children (MIS-C), a life-threatening condition distinct from COVID-19 that presents with high fevers and multiorgan injury, often including coronary aneurysms, ventricular failure, or myocarditis (Cheung et al, 2020;Feldstein et al, 2020Feldstein et al, , 2021Licciardi et al, 2020;Riphagen et al, 2020;Verdoni et al, 2020;Whittaker et al, 2020).…”

Section: Characteristics Of Pediatric Blood Donors With Covid-19 Mis-c or Sars-cov-2-uninfected Controlsmentioning

confidence: 99%

“…Survival after infection with a pathogenic virus such as SARS-CoV-2 requires not only that the immune system control and eliminate the pathogen, but that disease tolerance mechanisms limit tissue damage caused by the pathogen or by host inflammatory responses (Ayres, 2020a;McCarville and Ayres, 2018;Medzhitov et al, symptomatic from asymptomatic infection (Cevik et al, 2021;Jones et al, 2021;Lee et al, 2020;Lennon et al, 2021;Ra et al, 2021;Yang et al, 2021). This discrepancy between SARS-CoV-2 viral load and the severity of COVID-19 is especially pronounced in children, who rarely have severe COVID-19 (Charles Bailey et al, 2020;Li et al, 2020;Lu et al, 2020;Poline et al, 2020), though viral load may be comparable to that in adults with severe COVID-19 (Heald-Sargent et al, 2020;LoTempio et al, 2021;Yonker et al, 2020). These observations suggest that age-dependent, disease tolerance mechanisms influence the severity of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection

Silverstein

Wang

Manickas-Hill

et al. 2021

Preprint

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BACKGROUNDRisk of severe coronavirus disease 2019 (COVID-19) increases with age, is greater in males, and is associated with decreased numbers of blood lymphoid cells. Though the reasons for these robust associations are unclear, effects of age and sex on innate and adaptive lymphoid subsets, including on homeostatic innate lymphoid cells (ILCs) implicated in disease tolerance, may underlie the effects of age and sex on COVID-19 morbidity and mortality.METHODSFlow cytometry was used to quantitate subsets of blood lymphoid cells from people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comparing those hospitalized with severe COVID-19 (n=40) and those treated as outpatients for less severe disease (n=51). 86 healthy individuals served as controls. The relationship between abundance of specific blood lymphoid cell types, age, sex, hospitalization, duration of hospitalization, and elevation of blood markers for systemic inflammation, was determined using multiple regression.RESULTSAfter accounting for effects of age and sex, hospitalization for COVID-19 was associated with 1.78-fold fewer ILCs (95%CI: 2.34–1.36; p = 4.55 x 10−5) and 2.31-fold fewer CD16+ natural killer (NK) cells (95%CI: 3.1–1.71; p = 1.04 x 10−7), when compared to uninfected controls. Among people infected with SARS-CoV-2, the odds ratio for hospitalization, adjusted for age, sex, and duration of symptoms, was 0.413 (95%CI: 0.197–0.724; p = 0.00691) for every 2-fold increase in ILCs. In addition, higher ILC abundance was associated with less time spent in the hospital and lower levels of blood markers associated with COVID-19 severity: each two-fold increase in ILC abundance was associated with a 9.38 day decrease in duration of hospital stay (95% CI: 15.76–3.01; p= 0.0054), and decrease in blood C-reactive protein (CRP) by 46.29 mg/L (95% CI: 71.34–21.24; p = 6.25 x 10−4), erythrocyte sedimentation rate (ESR) by 11.04 mm/h (95% CI: 21.94–0.13; p = 0.047), and the fibrin degradation product D-dimer by 1098.52 ng/mL (95% CI: 1932.84–264.19; p = 0.011).CONCLUSIONSBoth ILCs and NK cells were depleted in the blood of people hospitalized for severe COVID-19, but, among lymphoid cell subsets, only ILC abundance was independently associated with the need for hospitalization, duration of hospital stay, and severity of inflammation. These results indicate that, by promoting disease tolerance, homeostatic ILCs protect against morbidity and mortality in SARS-CoV-2 infection, and suggest that reduction in the number of ILCs with age and in males accounts for the increased risk of severe COVID-19 in these demographic groups.

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Section: Characteristics Of Pediatric Blood Donors With Covid-19 Mis-c or Sars-cov-2-uninfected Controlsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection

Silverstein

Wang

Manickas-Hill

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Children are less likely than adults to have severe disease when infected with SARS-CoV-2 despite having viral loads as high as adults ( Bailey et al, 2021 ; Heald-Sargent et al, 2020 ; Li et al, 2020 ; LoTempio et al, 2021 ; Lu et al, 2020 ; Poline et al, 2020 ; Yonker et al, 2020 ). Rarely, after SARS-CoV-2 clearance from the upper airways, children can develop severe Multisystem Inflammatory Syndrome in Children (MIS-C), a life-threatening condition distinct from COVID-19 that presents with high fevers and multiorgan injury, often including coronary aneurysms, ventricular failure, or myocarditis ( Cheung et al, 2020 ; Feldstein et al, 2021 ; Feldstein et al, 2020 ; Licciardi et al, 2020 ; Riphagen et al, 2020 ; Verdoni et al, 2020 ; Whittaker et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, SARS-CoV-2 viral load does not reliably discriminate symptomatic from asymptomatic infection (Cevik et al, 2021;Jones et al, 2021;Lee et al, 2020;Lennon et al, 2021;Ra et al, 2021;Yang et al, 2021). This discrepancy between SARS-CoV-2 viral load and the severity of COVID-19 is especially pronounced in children, who rarely have severe COVID-19 (Charles Bailey et al, 2020;Li et al, 2020;Lu et al, 2020;Poline et al, 2020), though viral load may be comparable to that in adults with severe COVID-19 (Heald-Sargent et al, 2020;LoTempio et al, 2021;Yonker et al, 2020). These observations suggest that age-dependent, disease tolerance mechanisms influence the severity of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection

Silverstein

Wang

Manickas-Hill

et al. 2022

eLife

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Background: Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations.Methods: Multiple regression was used to determine the relationship between abundance of specific blood lymphoid cell types, age, sex, requirement for hospitalization, duration of hospitalization, and elevation of blood markers of systemic inflammation, in adults hospitalized for severe COVID-19 (n=40), treated for COVID-19 as outpatients (n=51), and in uninfected controls (n=86), as well as in children with COVID-19 (n=19), recovering from COVID-19 (n=14), MIS-C (n=11), recovering from MIS-C (n=7), and pediatric controls (n=17).Results: This observational study found that the abundance of innate lymphoid cells (ILCs) decreases more than 7-fold over the human lifespan - T cell subsets decrease less than 2-fold - and is lower in males than in females. After accounting for effects of age and sex, ILCs, but not T cells, were lower in adults hospitalized with COVID-19, independent of lymphopenia. Among SARS-CoV-2-infected adults, the abundance of ILCs, but not of T cells, correlated inversely with odds and duration of hospitalization, and with severity of inflammation. ILCs were also uniquely decreased in pediatric COVID-19 and the numbers of these cells did not recover during follow-up. In contrast, children with MIS-C had depletion of both ILCs and T cells, and both cell types increased during follow-up. In both pediatric COVID-19 and MIS-C, ILC abundance correlated inversely with inflammation. Blood ILC mRNA and phenotype tracked closely with ILCs from lung. Importantly, blood ILCs produced amphiregulin, a protein implicated in disease tolerance and tissue homeostasis. Among controls, the percentage of ILCs that produced amphiregulin was higher in females than in males, and people hospitalized with COVID-19 had a lower percentage of ILCs that produced amphiregulin than did controls.Conclusions: These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS-CoV-2 infection, and that lower ILC abundance contributes to increased COVID-19 severity with age and in males.Funding: This work was supported in part by the Massachusetts Consortium for Pathogen Readiness and NIH grants R37AI147868, R01AI148784, F30HD100110, 5K08HL143183.

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“…LOTEMPIO et al (2021) reported a case of a neonate with COVID-19 symptoms who was admitted to the Children’s National Hospital. SARS-CoV-2 RT-PCR detected an extremely high viral rate, and the nonsynonymous amino acid substitution N679S was identified [ 91 ]. Data analysis confirmed the presence of the D614G mutation in the viral genome, which is present in the majority of global samples.…”

Section: Sars-cov-2 Variants and Potential Differences In Neonates’ I...mentioning

confidence: 99%

SARS-CoV-2 Infection and Possible Neonatal Neurological Outcomes: A Literature Review

Moraes

Souza

Alves

et al. 2022

Viruses

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The virus responsible for COVID-19 is designated “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), a highly transmissible and pathogenic coronavirus. Although people of all ages are susceptible to SARS-CoV-2 infection, clinical manifestations may vary with age. The response of neonates to SARS-CoV-2 infection or exposure differs from that of children and adults. Encephalitis due to viral infections in the central nervous system (CNS) and childhood multisystem inflammatory syndrome (MIS-C) are some of the possible neonatal consequences of SARS-CoV-2 infection. This review aims to verify possible neonatal neurological outcomes after SARS-CoV-2 infection. Overall, the cellular and molecular basis of the neurological sequelae of SARS-CoV-2 in neonates remains unclear, and attempts to elucidate the pathophysiology of COVID-19 involve a comparison with the mechanism of other viral diseases. There are a considerable number of case reports in the literature exploring neurological outcomes in the neonatal period. In this review, we present possible effects of SARS-CoV-2 in neonates, emphasizing the importance of monitoring this group. The mechanisms of SARS-CoV-2 entry into the CNS have not yet been fully elucidated, and the potential severity of SARS-CoV-2 infection in neonates, as well as the possible short- and long-term neurological sequelae, remain unclear.

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Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak

Cited by 6 publications

References 30 publications

Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection

Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection

Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection

SARS-CoV-2 Infection and Possible Neonatal Neurological Outcomes: A Literature Review

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