Omicron severity: milder but not mild

Nealon, Joshua; Cowling, Benjamin J.

doi:10.1016/s0140-6736(22)00056-3

Cited by 140 publications

(130 citation statements)

References 8 publications

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“…This study demonstrates efficacy of molnupiravir against relevant SARS-CoV-2 VOC alpha, gamma, delta, and omicron in human airway organoids, the ferret transmission model, and the Roborovski dwarf hamster model of life-threatening viral pneumonia. We show that the dwarf hamsters provide a robust experimental system to explore degrees of pathogenicity of different VOC, which correlated well with clinical reports showing, for instance, higher rates of severe disease and hospitalization associated with delta 30-32 than omicron 33 . The implications of these efficacy models for the anticipated pharmacological impact of molnupiravir are four-fold:…”

Section: Discussionsupporting

confidence: 82%

SARS-CoV-2 variant of concern type and biological sex affect efficacy of molnupiravir in dwarf hamster model of severe COVID-19

Lieber

Cox

Sourimant

et al. 2022

Preprint

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SARS-CoV-2 variants of concern (VOC) have triggered distinct infection waves in the coronavirus disease 2019 (COVID-19) pandemic, culminating in currently all-time high incidence rates of VOC omicron. Orally available direct-acting antivirals such as molnupiravir promise to improve disease management and limit SARS-CoV-2 spread. However, molnupiravir efficacy against VOC delta was questioned based on clinical trial results and its potency against omicron is unknown. This study evaluates molnupiravir against a panel of relevant VOC in three efficacy models: primary human airway epithelium organoids, the ferret model of upper respiratory disease, and a lethal Roborovski dwarf hamster efficacy model of severe COVID-19-like acute lung injury. All VOC were equally efficiently inhibited by molnupiravir in cultured cells and organoids. Treatment consistently reduced upper respiratory VOC shedding in ferrets and prevented viral transmission. Pathogenicity in the dwarf hamsters was VOC-dependent and highest for gamma, omicron, and delta with fulminant lung histopathology. Oral molnupiravir started 12 hours after infection resulted in complete survival of treated dwarf hamsters independent of challenge VOC. However, reduction in lung virus differed VOC-dependently, ranging from one (delta) to four (gamma) orders of magnitude compared to vehicle-treated animals. Dwarf hamsters infected with VOC omicron showed significant individual variation in response to treatment. Virus load reduction was significant in treated males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir seen in human trials and alerts that therapeutic benefit of approved antivirals must be continuously reassessed in vivo as new VOC emerge.

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Section: Discussionsupporting

confidence: 82%

SARS-CoV-2 variant of concern type and biological sex affect efficacy of molnupiravir in dwarf hamster model of severe COVID-19

Lieber

Cox

Sourimant

et al. 2022

Preprint

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“…Omicron variant harbors 37 mutations in the spike protein (Mannar et al, 2022). Although, Omicron seen to be more contagious, data indicate it is milder than other variants (Nealon and Cowling, 2022). Therefore, we hypothesized that unvaccinated adult patients infected with Omicron variant will display decreased NET levels when compared to those infected with earlier strains (Alpha).…”

Section: Covid-19 Patients Infected With Omicron Variant Display Decr...mentioning

confidence: 99%

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

Carmona-Rivera¹,

Dobbs²,

Markowitz³

et al. 2022

Preprint

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Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as COVID toes, remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

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“…Omicron has a higher affinity for human ACE2 receptors compared with the Delta variant, indicating a higher potential for transmission [23,24]. Initial studies showed that infection by the Omicron variant produced less severe disease and significantly reduced the odds of hospital admission compared with earlier variants, such as Delta [25,26]. However, the onset of Omicron circulation raised concerns about Panbio TM COVID-19 Ag RDT performance against this VOC as it incorporated mutations and deletions in the N protein that could potentially affect antigen binding.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Panbio™ COVID-19 Antigen Rapid Diagnostic Test in subjects infected with Omicron using different specimens

Galiez

Bomfim

Mariani

et al. 2022

Preprint

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Community testing is a crucial tool for the early identification of SARS-CoV-2 infection and transmission control. The emergence of the highly mutated Omicron variant (B.1.1.259) raised concerns about its primary site of replication, impacting sample collection, and its detectability by rapid antigens tests. We tested the Antigen Rapid Diagnostic Test (Ag-RDT) performance using nasal, oral, and saliva specimens for COVID-19 diagnosis in 192 symptomatic individuals, using RT-qPCR from nasopharyngeal samples as control. Variant of Concern (VOC) investigation was determined by the 4Plex SARS-CoV-2 screening kit. SARS-CoV-2 positivity rate was 66.2%, with 99% of the positive samples showing an amplification profile consistent with that of the Omicron variant. Nasal Ag-RDT showed higher sensitivity (89%) than oral (12.6%) and saliva (22.1%) Ag-RDTs. Our data showed the good performance of the Ag-RDT in a pandemic scenario dominated by the Omicron VOC. Furthermore, our data also demonstrated that nasal specimens perform better than oral and saliva ones for Omicron Ag-RDT detection.

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Omicron severity: milder but not mild

Cited by 140 publications

References 8 publications

SARS-CoV-2 variant of concern type and biological sex affect efficacy of molnupiravir in dwarf hamster model of severe COVID-19

SARS-CoV-2 variant of concern type and biological sex affect efficacy of molnupiravir in dwarf hamster model of severe COVID-19

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

Evaluation of the Panbio™ COVID-19 Antigen Rapid Diagnostic Test in subjects infected with Omicron using different specimens

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