Dataset Information

Atypical Prolonged Viral Shedding With Intra-Host SARS-CoV-2 Evolution in a Mildly Affected Symptomatic Patient.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is caused by a respiratory virus with a wide range of manifestations, varying from asymptomatic to fatal cases, with a generally short outcome. However, some individuals present long-term viral shedding. We monitored 38 individuals who were mildly affected by the SARS-CoV-2 infection. Out of the total studied population, three (7.9%) showed atypical events regarding the duration of positivity for viral RNA detection. In one of these atypical cases, a previously HIV-positive male patient presented a SARS-CoV-2 RNA shedding and subgenomic RNA (sgRNA) detected from the upper respiratory tract, respectively, for 232 and 224 days after the onset of the symptoms. The SARS-CoV-2 B.1.1.28 lineage, one of the most prevalent in Brazil in 2020, was identified in this patient in three serial samples. Interestingly, the genomic analyses performed throughout the infectious process showed an increase in the genetic diversity of the B.1.1.28 lineage within the host itself, with viral clearance occurring naturally, without any intervention measures to control the infection. Contrasting widely spread current knowledge, our results indicate that potentially infectious SARS-CoV-2 virus might be shed by much longer periods by some infected patients. This data call attention to better adapted non-pharmacological measures and clinical discharge of patients aiming at preventing the spread of SARS-CoV-2 to the population.

SUBMITTER: Cunha MDP

PROVIDER: S-EPMC8661089 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Atypical Prolonged Viral Shedding With Intra-Host SARS-CoV-2 Evolution in a Mildly Affected Symptomatic Patient.

Cunha Marielton Dos Passos MDP Vilela Ana Paula Pessoa APP Molina Camila Vieira CV Acuña Stephanie Maia SM Muxel Sandra Marcia SM Barroso Vinícius de Morais VM Baroni Sabrina S Gomes de Oliveira Lilian L Angelo Yan de Souza YS Peron Jean Pierre Schatzmann JPS Góes Luiz Gustavo Bentim LGB Campos Angélica Cristine de Almeida ACA Minóprio Paola P

Frontiers in medicine 20211126

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is caused by a respiratory virus with a wide range of manifestations, varying from asymptomatic to fatal cases, with a generally short outcome. However, some individuals present long-term viral shedding. We monitored 38 individuals who were mildly affected by the SARS-CoV-2 infection. Out of the total studied population, three (7.9%) showed atypical events regarding the duration of positivity for viral RNA detection. In o ...[more]

PMID: 34901074

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Project description:Long-term infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to virus dispersion and the control of coronavirus disease 2019 (COVID-19) pandemic. The reason why some people have prolonged infection and how the virus persists for so long are still not fully understood. Recent studies suggested that the accumulation of intra-host single nucleotide variants (iSNVs) over the course of the infection might play an important role in persistence as well as emergence of mutations of concern. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during prolonged infection. Thirty-three patients who remained reverse transcription polymerase chain reaction (RT-PCR) positive in the nasopharynx for on average 18 days from the symptoms onset were included in this study. Whole-genome sequences were obtained for each patient at two different time points. Phylogenetic, populational, and computational analyses of viral sequences were consistent with prolonged infection without evidence of coinfection in our cohort. We observed an elevated within-host genomic diversity at the second time point samples positively correlated with cycle threshold (Ct) values (lower viral load). Direct transmission was also confirmed in a small cluster of healthcare professionals that shared the same workplace by the presence of common iSNVs. A differential accumulation of missense variants between the time points was detected targeting crucial structural and non-structural proteins such as Spike and helicase. Interestingly, longitudinal acquisition of iSNVs in Spike protein coincided in many cases with SARS-CoV-2 reactive and predicted T cell epitopes. We observed a distinguishing pattern of mutations over the course of the infection mainly driven by increasing A→U and decreasing G→A signatures. G→A mutations may be associated with RNA-editing enzyme activities; therefore, the mutational profiles observed in our analysis were suggestive of innate immune mechanisms of the host cell defense. Therefore, we unveiled a dynamic and complex landscape of host and pathogen interaction during prolonged infection of SARS-CoV-2, suggesting that the host's innate immunity shapes the increase of intra-host diversity. Our findings may also shed light on possible mechanisms underlying the emergence and spread of new variants resistant to the host immune response as recently observed in COVID-19 pandemic.

Project description:IntroductionMildly symptomatic cases of Covid-19 in previously-well individuals form the majority of infections and also serve as potent vectors of transmission. The factors affecting the duration of SARS-CoV-2 RNA viral shedding (DVS) in these patients remain largely unknown.ObjectivesTo perform a systematic analysis of the clinical, radiologic, laboratory investigations in patients with few comorbidities infected with mild Covid-19 to identify factors associated with the DVS.MethodsIn this retrospective cohort study, patients with mild or asymptomatic Covid-19 were included. Baseline characteristics including age, nationality, comorbidities, concomitant medications, and type of isolation arrangement in the facility (single or in pairs) were collected. Clinical features and radiologic/haematologic findings were also collected. Taking day 28 as the cut-off, 187 patients who had a negative swab result up to day 28 (no prolonged DVS) were compared to 126 patients with a persistently positive result on or after day 28 (prolonged DVS).ResultsOf 964 consecutive patients included, 851 (88.3%) patients were symptomatic. 266 patients had a documented negative RT-PCR assay with a median DVS of 25 days (range: 13 to 96 days; interquartile range (IQR): 22 to 33 days). Patients isolated in pairs were associated with prolonged DVS (OR: 2.7; 95% CI: 1.7 to 4.5; p<0.0001) compared to those isolated individually. Among vital signs, only tachycardia was associated with prolonged DVS (OR: 2.6; 95% CI: 1.0 to 7.1; p = 0.03). Amongst investigations, only a raised CRP was associated with prolonged DVS (OR: 2.7; 95% CI: 1.1 to 6.8; p = 0.02).ConclusionsIn young, mildly symptomatic Covid-19 patients, prolonged DVS was associated with being isolated in pairs compared to individually. In situations where a negative RT-PCR test result is required, retesting in patients who were not isolated individually, or who had baseline tachycardia or a raised CRP, may be delayed to increase the yield of a negative result.

Project description:ObjectiveTo analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment.MethodsA total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time.ResultMost patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8-15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8-15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50-64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker.ConclusionsOur results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Dataset Information

Atypical Prolonged Viral Shedding With Intra-Host SARS-CoV-2 Evolution in a Mildly Affected Symptomatic Patient.

Publications

Atypical Prolonged Viral Shedding With Intra-Host SARS-CoV-2 Evolution in a Mildly Affected Symptomatic Patient.

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