Poster ▸ COVID-19
P 155A refine analysis on SARS-CoV-2 omicron variability in infected immunocompromised individuals
Authors: M.C. Bellocchi1, L. Carioti1, G. Marchegiani1, L. Coppola2, M. Iannetta2, L. Duca1, A. Di Lorenzo2, L. Alborghetti2, L. Piermatteo1, V. Malagnino2, L. Benedetti1, M.M. Santoro1, M. Andreoni2, L. Sarmati2, F. Ceccherini-Silberstein1
Affiliation: 1University of Rome Tor Vergata, Rome, Italy, 2University Hospital of Rome Tor Vergata, Rome, Italy
ABSTRACT
Background: We aim to characterize SARS-CoV-2 omicron variability with a focus in immunocompromised patients (IPs).
Methods: This retrospective study includes SARS-CoV-2 infected hospitalized and non-hospitalized IPs (HIP/NHIP) and non-IPs (HP/NHP). Nasopharyngeal swabs (NS) were collected over Jan-Dec 2022 and SARS-CoV-2 genome sequences were obtained by Miseq-platform. Additional mutations (AMs) (intra-host prevalence>20%) not present in sublineage consensus, were analyzed in spike, nucleocapsid and nonstructural proteins (RNA-dependent RNA polymerase, main-protease, papain-like-protease, helicase, Orf6 and Orf9b).
Results: 211 SARS-CoV-2 omicron infected individuals (126 NHIP, 12 HIP, 57 NHP, 16 HP) were characterized: 49.8% were female, with a median [IQR] age of 61[50-72] yrs and 10.0% reporting no SARS-CoV-2 vaccination (Tab.1). IPs were younger (median[IQR]yrs: 58[48-69] in HIP+NHIP vs 67[53-77] in HP+NHP, p= 0.0015). Different rate of pneumonia was observed, particularly higher in HP (0%, 0%, 58.0%, 93.8% in NHIP, NHP, HIP, HP, respectively p<0.001) and higher frequency of no-vaccination was observed in hospitalized patients (37.5% HP, 25% HIP, vs 8.8% NHP and 5.6% NHIP, p<0.001).
Overall, 34 different Omicron sublineages were identified: BA.1.1(21.3%) the most prevalent, followed by BA.1/BA.2(17.5%), BA.2.9(7.6%) and BA.5.1(3.8%), without any significant different prevalence among the groups (Fig.1). About AMs analysis, 60.7% of individuals showed ≥ 1 AM, in ≥1 of the analyzed genes. A different prevalence of AMs in NHIP,HIP,NHP,HP groups was found only in spike (17.5%, 33.3%, 7%, 25%, p=0.041) and in the receptor binding domain (RBD, 3.9%, 16.7%, 0%, 12.5% p=0.015), respectively. Higher prevalence of AMs was observed in hospitalized (HIP+HP) vs non-hospitalized individuals (NHIP+NHP) in both spike (28.5% vs 14.2%, p=0.054) and RBD (14.3% vs 2.7%, p=0.019). These results correlate with the Δ days from first COVID-19 symptoms to NS sampling, that were significantly longer in hospitalized patients (median [IQR] days: 9[7-12] in HP vs 5[3-8] in HIP vs 4[3-5] in NHIP vs 4[3-5] in NHP p<0.001).
About innate response genes, in Orf6, the D61L mutation (typical of BA.2 or BA.4) was found with an overall prevalence of 36.5%. Its presence (as BA.2 and BA.4 infection) was higher in IPs (41.3% in HIP+NHIP vs 23.4% in HP+NHP,p=0.046) and less in hospitalized patients (17.8% in HIP+HP vs 39.3% in NHIP+NHP,p=0.028). In IPs, a higher prevalence of AMs in Orf9b was found in hospitalized patients (16.7% in HIP vs 2.4% NHIP,p=0.06).
AMs associated with resistance to mAbs (346K/446D/452R/445L/460KS) were found only in HIP and/or NHIP, while none of AMs associated with resistance to molnupiravir and nirmatrelvir was observed in the cohort.
Conclusion: We confirmed a higher variability in IPs, particularly when hospitalized. These results deserve further investigation in a larger population, specifically for Orf6 and Orf9b genes related to the innate antiviral response.
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