Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection With accumulation of mutations in a patient with poorly controlled Human Immunodeficiency Virus infection

Maponga, Tongai; Jeffries, Montenique; Tegally, Houriiyah; Sutherland, Andrew D.; Wilkinson, Eduan; Lessells, Richard J; Msomi, Nokukhanya; Zyl, Gert van; Oliveira, Túlio de; Preiser, Wolfgang

doi:10.1093/cid/ciac548

Cited by 43 publications

(33 citation statements)

References 12 publications

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“…The identification of risk factors for a reduced response to SARS-CoV-2 vaccines in PLWH is important as it will help to improve vaccination strategies in PLWH. A good understanding of vaccination response in PLWH is even more important now that variants of concern (VOCs) continue to arise and partially escape vaccine-induced immunity [ 15 ], especially considering the possibility of VOCs arising in PLWH unable to clear the virus due to an untreated HIV infection [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Hensley¹,

Jongkees²,

GeurtsvanKessel³

et al. 2022

PLoS Med

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Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. Methods and findings We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44–60] years, 85.5% male) and 440 controls (median age 43 [IQR 33–53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/μL (IQR 520–913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322–1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508–0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250–500 cells/μL (2.845, 95% CI 1.876–4.314, p < 0.001) or >500 cells/μL (2.936, 95% CI 1.961–4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286–0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. Conclusions After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. Trial registration The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214.

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Section: Introductionmentioning

confidence: 99%

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Hensley¹,

Jongkees²,

GeurtsvanKessel³

et al. 2022

PLoS Med

View full text Add to dashboard Cite

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“…It also has increased environmental stability, suggesting that transmission via the airborne route may be more frequent 32,33 . It may also replicate faster in human respiratory epithelial cells, 34 and this could lead to more rapid accumulation of mutations and intrahost evolution in chronic infections 35,36 . Recently, Lai et al found that viral RNA shedding of exhaled breath aerosols in patients with Alpha, Delta, and Omicron variants increased, compared with previous variants of concerns, but there was no significant difference in peak RNA shedding between Delta and Omicron variants 36 .…”

Section: Discussionmentioning

confidence: 99%

Comparison of secondary attack rate and viable virus shedding between patients with SARS‐CoV‐2 Delta and Omicron variants: A prospective cohort study

Kang

Kim

Park

et al. 2022

Journal of Medical Virology

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There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID‐19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS‐CoV‐2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID‐19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1−7], vs. 8.5 days, IQR [5–12 days], p < 0.001). Multivariable analysis revealed that moderate‐to‐critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster‐vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.

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“…In numerous studies, it was discovered that Africans have higher nucleotide and haplotype diversity than non-Africans [ 5 , 28 , 29 , 30 ]. In another study, ACE2 receptors are presented with some different nonsynonymous mutations in African populations which were identified as signatures of selection affecting variation at regulatory regions related to ACE2 expression [ 46 ] along with multiple risk factors such as HIV coinfection, tuberculosis, anemia and population age [ 47 , 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

The Spike Protein of SARS-coV2 19B (S) Clade Mirrors Critical Features of Viral Adaptation and Coevolution

et al. 2022

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Pathogens including viruses evolve in tandem with diversity in their animal and human hosts. For SARS-coV2, the focus is generally for understanding such coevolution on the virus spike protein, since it demonstrates high mutation rates compared to other genome regions, particularly in the receptor-binding domain (RBD). Viral sequences of the SARS-coV2 19B (S) clade and variants of concern from different continents were investigated, with a focus on the A.29 lineage, which presented with different mutational patterns within the 19B (S) lineages in order to learn more about how SARS-coV2 may have evolved and adapted to widely diverse populations globally. Results indicated that SARS-coV2 went through evolutionary constrains and intense selective pressure, particularly in Africa. This was manifested in a departure from neutrality with excess nonsynonymous mutations and a negative Tajima D consistent with rapid expansion and directional selection as well as deletion and deletion–frameshifts in the N-terminal domain (NTD region) of the spike protein. In conclusion, we hypothesize that viral transmission during epidemics through populations of diverse genomic structures and marked complexity may be a significant factor for the virus to acquire distinct patterns of mutations within these populations in order to ensure its survival and fitness, explaining the emergence of novel variants and strains.

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Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection With accumulation of mutations in a patient with poorly controlled Human Immunodeficiency Virus infection

Cited by 43 publications

References 12 publications

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Comparison of secondary attack rate and viable virus shedding between patients with SARS‐CoV‐2 Delta and Omicron variants: A prospective cohort study

The Spike Protein of SARS-coV2 19B (S) Clade Mirrors Critical Features of Viral Adaptation and Coevolution

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