Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies.

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval [CI] 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days [95% CI 7.9, 14.4]) than for asymptomatic individuals (7.8 days [95% CI 6.1, 9.7]). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient's infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient's progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious.

Duration of SARS-CoV-2 shedding: A population-based, Canadian study.

INTRODUCTION: There is an evidence gap regarding the duration of SARS-CoV-2 shedding and of its variability across different care settings and by age, sex, income, and co-morbidities. Such evidence is part of understanding of infectivity and reinfection. We examine direct measures of viral shedding using a linked population-based health administrative dataset. METHODS: Laboratory and sociodemographic databases for Ontario, Canada were linked to identify those testing positive (RT-PCR) between Jan. 15 and April 30, 2020 who underwent subsequent testing by May 31, 2020. To maximise use of available data, we computed two shedding duration estimates defined as the time between initial positive and most recent positive (documented shedding) or second of two negative tests (documented resolution). We also report multivariable results using quantile regression to examine subgroup differences. RESULTS: In Ontario, of the 16,595 who tested positive before April 30, 2020, 6604 had sufficient subsequent testing to allow shedding duration calculation. Documented shedding median duration calculated in 4,889 (29% of 16,595) patients was 19 days (IQR 12-28). Documented resolution median duration calculated in 3,219 (19% of the 16,595) patients was 25 days (IQR 18-34). Long-term care residents had 3-5 day longer shedding durations using both definitions. Shorter documented shedding durations of 2-4 days were observed in those living in higher income neighbourhoods. Shorter documented resolution durations of 2-3 days were observed at the 25th% of the distribution in those aged 20-49. Only 11.5% of those with definitive negative test results reverted to negative status by day 14. CONCLUSIONS: Viral shedding continued well beyond 14 days among this large subset of a population-based group with COVID-19, and longer still for long-term care residents and those living in less affluent neighborhoods. Our findings do not speak to duration of infectivity but are useful for understanding the expected duration of RT-PCR positivity and for identifying reinfection.

Factors Influencing Viral Clearance in Mild COVID-19 and Clinical Characteristics of Asymptomatic Patients.

BACKGROUND: The outbreak of coronavirus disease (COVID-19) has become a global public health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of patients with COVID-19 in Anhui and to identify predictors of viral clearance. METHODS: We retrospectively analyzed the data collected from discharged patients with laboratory-confirmed SARS-CoV-2 infections. We compared clinical features between viral clearance and viral persistence, and evaluated factors associated with SARS-CoV-2 shedding using multiple linear regression. RESULTS: Among the 83 patients involved in the study, the median age was 43 years, while 60.2% were male, 35.4% had comorbidities, and the mortality was zero. The median time from illness onset to admission was 5 days (interquartile range (IQR), 2-7 days), and the median time from the illness onset to SARS-CoV-2 RNA detection was 16 days (IQR, 13-18 days). The factors influencing viral clearance were as follows: (1) delayed admission (beta 1.057, 95% CI 0.810-1.304; p ≤ 0.001) and (2) underlying comorbidities (beta 1.907, 95% CI 0.198-3.616; p = 0.029). No significant differences were observed in the length of stay (p = 0.246) and pneumonia between asymptomatic and symptomatic patients based on computed tomography (CT) (p = 0.124). CONCLUSIONS: Delayed admission and underlying comorbidities may effectively predict SARS-CoV-2 RNA clearance. For those infected with SARS-CoV-2, even asymptomatic patients without any clinical symptoms should be traced and isolated. This practice may reduce the spread of SARS-CoV-2 and slow the COVID-19 pandemic caused by the virus. Clinical Trial Registration Number: This trial is registered with 2020-051.

High-density lipoprotein cholesterol as a factor affecting virus clearance in covid-19 patients.

OBJECTIVE: There were COVID-19 patients with SARS-COV-2 nucleic acid long-term positive. This article aims to understand the relevant factors that affect SARS-COV-2 clearance time. METHODS: The clinical data of 115 COVID-19 patients with SARS-COV-2 nucleic acid positive time exceeding 14 days were collected retrospectively, and the relationship between clinical characteristics, chest CT scans, blood cells, biochemical indicators, and the time of viral nucleic acid turning negative were analyzed. RESULTS: The time from symptom onsets to nucleic acid turning negative was (32.5 ± 8.7) days in this group of patients. The time of nucleic acid turning negative: no fever group was longer than fever group, diabetes group was longer than no comorbidity group, elevated levels of ALT (alanine aminotransferase), or GLU (fasting blood glucose) group, decreased levels of ALB (albumin) group or HDLC (high-density lipoprotein cholesterol) group was longer than it's normal group separately (P < 0.05). Cox multivariate regression analysis showed that ALT [odds ratio (OR): 2.164 (95% CI: 1.276-3.670), P = 0.004], GLU [OR: 2.064 (95% CI: 1.195-3.566), P = 0.009] and HDLC [OR: 0.527 (95% CI: 0.307-0.907), P = 0.021] were independent factors which affected the time of nucleic acid turning negative. CONCLUSIONS: ALT, GLU and HDLC were independent factors that influenced the time of nucleic acid turning negative. Although diabetes or hyperglycemia is a known risk factor, HDLC is the first to be identified, clinicians should be aware of dyslipidemia in covid-19 patients.

Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020.

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.

Persistent viral RNA shedding after COVID-19 symptom resolution in older convalescent plasma donors.

INTRODUCTION: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for a worldwide pandemic. While the medical community understands the mode of viral transmission, less is known about how long viral shedding occurs once viral symptoms have resolved. Our objective was to determine how long the SARS-CoV-2 remains detectable following self-reporting of viral symptom resolution. METHODS: This study was approved by the University of Wisconsin Institutional Review Board. A cohort of patients who were previously SARS-CoV-2 positive less than 28 days after self-reported symptom resolution were retested for proof of viral recovery by nasal swab reverse transcriptase polymerase chain reaction for SARS-CoV-2 RNA. RESULTS: A total of 152 potential participants were screened, of which 5 declined, 54 were ineligible, and 93 were recruited; 86 of 93 completed testing. Eleven of 86 (13%) were still positive at a median of 19 days (range, 12-24 days) after symptom resolution. Positive participants were significantly older than negative participants (mean, 54 years; 95% confidence interval [CI], 44-63 vs 42 years; 95% CI, 38-46; P = .024). CT values were significantly, inversely associated with age (ß = -.04; r2 = 0.389; P = .04). The number of days since symptom recovery was not apparently different between positive and negative participants. CONCLUSION: We found evidence of persistent viral shedding in nasopharyngeal secretions more than 2 weeks after resolution of symptoms from confirmed COVID-19 infection. Persistent shedding was more common in older participants, and viral load was higher among older positive participants. These results underscore the necessity of testing COVID-19 convalescent plasma donors less than 28 days after symptom resolution.