Risk factors for prolonged viral RNA shedding in patients with COVID-19; a nested case-control study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic continues to have a global impact. The behavior and viral course of severe acute respiratory syndrome coronavirus (SARS-CoV-2) remains unpredictable. We aimed to investigate the prediction factors associated with prolonged viral shedding in COVID-19 patients. METHODOLOGY: This is a retrospective, nested, case-control study with 155 confirmed COVID-19 infected patients divided into two groups based on nucleic acid conversion time (NCT), a prolonged group (viral RNA shedding >14 days, n = 31) and a non-prolonged group (n = 124). RESULTS: The mean age of participants was 57.16 years, and 54.8% were male. Inpatient numbers were 67.7% across both groups. No statistically significant differences between the two groups were observed in terms of clinical manifestation, comorbidities, computer tomography, severity index, antiviral treatment, and vaccination. However, C-reactive protein and D-dimer levels were significantly higher in the prolonged group (p = 0.01; p = 0.01). Using conditional logistic regression analysis, D-dimer and bacterial co-infection were found to be independent factors associated with the prolonged NCT (OR: 1.001, 95% CI: 1.000-1.001, p = 0.043; OR: 12.479, 95% CI: 2.701-57.654, p = 0.001 respectively). We evaluated the diagnostic value of the conditional logistic regression model by using receiver operating characteristic curve analysis. The area under the curve was 0.7 (95% Cl: 0.574-0.802; p < 0.001). CONCLUSIONS: Our study design included controlling confounders. We showed a clear result associating predicting factors with prolonged NCT of SARS-CoV-2. D-dimer level and bacterial co-infection were considered as independent predictors of prolonged NCT.

Airborne virus shedding of the alpha, delta, omicron SARS-CoV-2 variants and influenza virus in hospitalized patients.

Airborne transmission is an important transmission route for the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological data indicate that certain SARS-CoV-2 variants, like the omicron variant, are associated with higher transmissibility. We compared virus detection in air samples between hospitalized patients infected with different SARS-CoV-2 variants or influenza virus. The study was performed during three separate time periods in which subsequently the alpha, delta, and omicron SARS-CoV-2 variants were predominant. In total, 79 patients with coronavirus disease 2019 (COVID-19) and 22 patients with influenza A virus infection were included. Collected air samples were positive in 55% of patients infected with the omicron variant in comparison to 15% of those infected with the delta variant (p < 0.01). In multivariable analysis, the SARS-CoV-2 omicron BA.1/BA.2 variant (as compared to the delta variant) and the viral load in nasopharynx were both independently associated with air sample positivity, but the alpha variant and COVID-19 vaccination were not. The proportion of positive air samples patients infected with the influenza A virus was 18%. In conclusion, the higher air sample positivity rate of the omicron variant compared to previous SARS-CoV-2 variants may partially explain the higher transmission rates seen in epidemiological trends.

Chronological changes of viral shedding in adult inpatients with Omicron infection in Shanghai, China.

Background: Coronavirus disease 2019 (COVID-19) caused by the Omicron variant occurred in Shanghai, China, but its clinical characteristics and virology have not been comprehensively described. Methods: This retrospective cohort study included adult inpatients (≥18 years) diagnosed with COVID-19 at Changhai Hospital. Laboratory and clinical data were obtained from electronic medical records to investigate the clinical characteristics of COVID-19 and the variations in the patients' laboratory indexes were examined. Results: The symptoms of COVID-19 caused by the Omicron variant were relatively mild. Upper respiratory tract specimens yielded higher positive detection rates than lower respiratory tract and intestinal specimens. Peak COVID-19 viral load was reached at the time of admission; quantification cycle (Cq) values increased to approximately 35 after 8.54 days. In vivo viral shedding duration correlated with age and disease severity (p<0.05). The older the patient and the more severe the disease, the longer the duration of viral shedding was. Portion parameters of blood routine, coagulative function, clinical chemistry, and inflammatory factor showed a certain correlation with the SARS-CoV-2 viral load. Conclusions: Virus replication and shedding are rapid in Omicron-positive patients; COVID-19 in these patients is characterized by acute onset, mild symptoms, and fast recovery. Older patients and those with more severe disease demonstrate prolonged virus shedding. Routine hematological indexes can reveal disease severity and help clinically evaluate the patient's condition.

Impact of antibody-level on viral shedding in B.1.617.2 (Delta) variant-infected patients analyzed using a joint model of longitudinal and time-to-event data.

Knowledge of viral shedding remains limited. Repeated measurement data have been rarely used to explore the influencing factors. In this study, a joint model was developed to explore and validate the factors influencing the duration of viral shedding based on longitudinal data and survival data. We divided 361 patients infected with Delta variant hospitalized in Nanjing Second Hospital into two groups (≤ 21 days group and > 21 days group) according to the duration of viral shedding, and compared their baseline characteristics. Correlation analysis was performed to identify the factors influencing the duration of viral shedding. Further, a joint model was established based on longitudinal data and survival data, and the Markov chain Monte Carlo algorithm was used to explain the influencing factors. In correlation analysis, patients having received vaccination had a higher antibody level at admission than unvaccinated patients, and with the increase of antibody level, the duration of viral shedding shortened. The linear mixed-effects model showed the longitudinal variation of logSARS-COV-2 IgM sample/cutoff (S/CO) values, with a parameter estimate of 0.193 and a standard error of 0.017. Considering gender as an influencing factor, the parameter estimate of the Cox model and their standard error were 0.205 and 0.1093 (P = 0.608), the corresponding OR value was 1.228. The joint model output showed that SARS-COV-2 IgM (S/CO) level was strongly associated with the risk of a composite event at the 95% confidence level, and a doubling of SARS-COV-2 IgM (S/CO) level was associated with a 1.38-fold (95% CI: [1.16, 1.72]) increase in the risk of viral non-shedding. A higher antibody level in vaccinated patients, as well as the presence of IgM antibodies in serum, can accelerate shedding of the mutant virus. This study provides some evidence support for vaccine prevention and control of COVID-19 variants.

Duration of viable virus shedding and polymerase chain reaction positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract: a systematic review and meta-analysis.

OBJECTIVES: To assess the duration of viable virus shedding and polymerase chain reaction (PCR) positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract. METHODS: We systematically searched PubMed, Cochrane, and Web of Science for original articles reporting the duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in the upper respiratory tract from November 11, 2021 to December 11, 2022. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42022357349). We used the DerSimonian-Laird random-effects meta-analyses to obtain the pooled value and the 95% confidence intervals. RESULTS: We included 29 studies and 230,227 patients. The pooled duration of viable virus shedding of the SARS-CoV-2 Omicron variant in the upper respiratory tract was 5.16 days (95% CI: 4.18-6.14), and the average duration of PCR positivity was 10.82 days (95% CI: 10.23-11.42). The duration of viable virus shedding and PCR positivity of the SARS-CoV-2 Omicron variant in symptomatic patients was slightly higher than that in asymptomatic patients, but the difference was not significant (P >0.05). CONCLUSION: The current study improves our understanding of the status of the literature on the duration of viable virus shedding and PCR positivity of Omicron in the upper respiratory tract. Our findings have implications for pandemic control strategies and infection control measures.

Inactivated COVID-19 vaccine booster dose shortened the viral shedding time of patients infected with the Omicron variant BA.2.

OBJECTIVES: We assessed the effect of inactivated COVID-19 vaccine boosting immunization on the viral shedding time for patients infected with the Omicron variant BA.2. METHODS: We performed a real-world study by analyzing the outbreak data of patients infected with the COVID-19 Omicron variant BA.2 from March to May 2022 in Shanghai, China. Patients were categorized into three groups, including not fully vaccinated (zero and one dose), fully vaccinated (two doses), and booster-vaccinated (three doses). RESULTS: A total of 4443 patients infected with COVID-19 were included in the analysis. The proportion of viral shedding within 14 days in the three groups was 94.7%, 95.5%, and 96.7%, respectively (P <0.001). After adjusting for sex, age, underlying conditions, and clinical symptoms, the booster vaccination had a 29% increased possibility (hazard ratio: 1.29, 95% confidence interval: 1.18-1.41) of no detectable viral shedding within 14 days, whereas the fully vaccinated group had an 11% increased possibility of no detectable viral shedding (hazard ratio: 1.11, 95% confidence interval: 1.01-1.23). The effect of booster vaccination was more significant in males, the elderly, and people with underlying conditions or symptomatic infections. CONCLUSION: Our study confirmed that the booster vaccination could significantly shorten the viral shedding time of patients infected with the Omicron variant BA.2.

Synchronicity of viral shedding in molossid bat maternity colonies.

Infection dynamics in vertebrates are driven by biological and ecological processes. For bats, population structure and reproductive cycles have major effects on RNA virus transmission. On Reunion Island, previous studies have shown that parturition of pregnant females and aggregation of juvenile Reunion free-tailed bats (Mormopterus francoismoutoui) are associated with major increase in the prevalence of bats shedding RNA viruses. The synchronicity of such shedding pulses, however, is yet to be assessed between viruses but also maternity colonies. Based on 3422 fresh faeces collected every 2-5 weeks during four consecutive birthing seasons, we report the prevalence of bats shedding astroviruses (AstVs), coronaviruses (CoVs) and paramyxoviruses (PMVs) in two maternity colonies on Reunion Island. We found that the proportion of bats shedding viruses is highly influenced by sampling collection periods, and therefore by the evolution of the population age structure. We highlight that virus shedding patterns are consistent among years and colonies for CoVs and to a lesser extent for PMVs, but not for AstVs. We also report that 1% of bats harbour co-infections, with two but not three of the viruses, and most co-infections were due to CoVs and PMVs.

Short-Term Effectiveness of Oral Nirmatrelvir/Ritonavir Against the SARS-CoV-2 Omicron Variant and Culture-Positive Viral Shedding.

BACKGROUND: Information on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated. METHODS: Mild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days. RESULTS: A total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P = 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively. CONCLUSIONS: Nirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.

Comparison of culture-competent virus shedding duration of SARS-CoV-2 Omicron variant in regard to vaccination status: A prospective cohort study.

Previous studies have shown that fully vaccinated patients with SARS-CoV-2 Delta variants has shorter viable viral shedding period compared to unvaccinated or partially vaccinated patients. However, data about effects of vaccination against the viable viral shedding period in patients with SARS-CoV-2 Omicron variants were limited. We compared the viable viral shedding period of SARS-CoV-2 omicron variant regard to vaccination status. Saliva samples were obtained daily from patients with SARS-CoV-2 Omicron variant, and genomic assessments and virus culture was performed to those samples. We found no difference in viable viral shedding period between fully vaccinated and not or partially vaccinated, nor between 1st boostered vs non-boostered patients with SARS-CoV-2 Omicron variant.

Extended Viral Shedding of MERS-CoV Clade B Virus in Llamas Compared with African Clade C Strain.

Middle East respiratory syndrome coronavirus (MERS-CoV) clade B viruses are found in camelids and humans in the Middle East, but clade C viruses are not. We provide experimental evidence for extended shedding of MERS-CoV clade B viruses in llamas, which might explain why they outcompete clade C strains in the Arabian Peninsula.

The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households.

Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases including SARS-CoV-2. However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2- to 4.2-fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.

A linear SARS-CoV-2 DNA vaccine candidate reduces virus shedding in ferrets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 760 million cases and over 6.8 million deaths as of March 2023. Vaccination has been the main strategy used to contain the spread of the virus and to prevent hospitalizations and deaths. Currently, two mRNA-based vaccines and one adenovirus-vectored vaccine have been approved and are available for use in the U.S. population. The versatility, low cost, and rapid production of DNA vaccines provide important advantages over other platforms. Additionally, DNA vaccines efficiently induce both B- and T-cell responses by expressing the antigen within transfected host cells, and the antigen, after being processed into peptides, can associate with MHC class I or II of antigen-presenting cells (APCs) to stimulate different T cell responses. However, the efficiency of DNA vaccination needs to be improved for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been used successfully in the field of veterinary oncology, resulting in high rates of response after electrochemotherapy. Here, we evaluate the safety, immunogenicity, and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects. Additionally, the vaccine elicited neutralizing antibodies and T cell responses on day 42 post-immunization using a low dose of the linear DNA construct in a prime-boost regimen. Most importantly, vaccination significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.

Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai.

Objective: To 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. Methods: A 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. Result: Most 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. Conclusions: Our 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.

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2.

Background: This study explores the risk factors associated with viral shedding time in elderly Chinese patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron. Methods: Participants infected with SARS-CoV-2 omicron were enrolled in a retrospective study, and divided into two groups according to shedding time (≥10 days, "late clearance group" and <10 days, "early clearance group"). Results: A total of 180 patients were enrolled in the study (88 early, 92 late), with a median viral shedding time of 10 days and a mean age of 77.02 years. Prolonged SARS-CoV-2 omicron shedding was associated with old age (p = 0.007), lack of vaccination (p = 0.001), delayed admission to hospital after onset of diagnosis (p = 0.001), D-dimer (p = 0.003), and methylprednisolone treatment (p = 0.048). In multivariate analysis, vaccination (OR, 0.319, 95% CI, 0.130-0.786, p = 0.013), Paxlovid (OR, 0.259, 95% CI, 0.104-0.643, p = 0.004), and time from onset of diagnosis to admission (OR, 1.802, 95% CI, 1.391-2.355, p = 0.000) were significantly associated with viral clearance. Conclusions: Time from onset of diagnosis to hospitalization, lack of treatment with Paxlovid, and lack of vaccination were independent risk factors in elderly Chinese patients infected with SARS-CoV-2 omicron for prolonged viral shedding.

SARS-CoV-2 Genome Variations in Viral Shedding of an Immunocompromised Patient with Non-Hodgkin's Lymphoma.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is the most transmissible ß-coronavirus in history, affecting all population groups. Immunocompromised patients, particularly cancer patients, have been highlighted as a reservoir to promote accumulation of viral mutations throughout persistent infection. CASE PRESENTATION: We aimed to describe the clinical course and SARS-CoV-2 mutation profile for 102 days in an immunocompromised patient with non-Hodgkin's lymphoma and COVID-19. We used RT-qPCR to quantify SARS-CoV-2 viral load over time and whole-virus genome sequencing to identify viral lineage and mutation profile. The patient presented with a persistent infection through 102 days while being treated with cytotoxic chemotherapy for non-Hodgkin's lymphoma and received targeted therapy for COVID-19 with remdesivir and hyperimmune plasma. All sequenced samples belonged to the BA.1.1 lineage. We detected nine amino acid substitutions in five viral genes (Nucleocapsid, ORF1a, ORF1b, ORF13a, and ORF9b), grouped in two clusters: the first cluster with amino acid substitutions only detected on days 39 and 87 of sample collection, and the second cluster with amino acid substitutions only detected on day 95 of sample collection. The Spike gene remained unchanged in all samples. Viral load was dynamic but consistent with the disease flares. CONCLUSIONS: This report shows that the multiple mutations that occur in an immunocompromised patient with persistent COVID-19 could provide information regarding viral evolution and emergence of new SARS-CoV-2 variants.

Immunocompromised states caused the prolonged duration of viral shedding in middle-aged and elderly hemodialysis patients infected with the Omicron variant of COVID-19.

INTRODUCTION: To evaluate the impact of hemodialysis on the duration of viral shedding in middle-aged and elderly patients with the Omicron variant of COVID-19. METHODS: The study was a descriptive, paired cohort study. Hemodialysis participants (the HD group) aged 45-99 years infected with the Omicron variant of COVID-19 were matched (in a 1:2 ratio) with patients not undergoing hemodialysis (the non-HD group) according to age, gender, vaccination doses, and comorbidity. The duration of viral shedding and clinical data were collected. RESULTS: Ninety-nine patients met the inclusion criteria. The duration of recovery was significantly longer for HD patients than for non-HD patients (p < 0.05). Lower counts for CD45+ cells and lymphocytes, along with lower levels of albumin and hemoglobin were associated with a longer duration of viral shedding (p < 0.05). CONCLUSION: Hemodialysis patients with immunocompromised state, anemia, and hypoalbuminemia might lead to prolongation of the duration of viral shedding.