Prolonged Viral Shedding Research Articles

Prolonged viral shedding prediction on non-hospitalized, uncomplicated SARS-CoV-2 patients using their transcriptome data

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is identified as a highly transmissible coronavirus which threatens the world with this deadly pandemic. WHO reported that it spreads through contact, droplet, airborne, formite, fecal-oral, bloodborne, mother-to-child and animal-to-human. Hence, viral shedding has a huge impact on this pandemic. This study uses transcriptome data of coronavirus disease 2019 (COVID-19) patients to predict the prolonged viral shedding of the corresponding patient. This prediction starts with the transcriptome features which gives the lowest root mean squared value of 16.3±3.3 using top 25 feature selected using forward feature selection algorithm and linear regression algorithm. Then to see the impact of few non-molecular features in this prediction, they were added to the model one by one along with the selected transcriptome features. However, this study shows that those features do not have any impact on prolonged viral shedding prediction. Further this study predicts the day since onset in the same way. Here also top 25 transcriptome features selected using forward feature selection algorithm gives a comparably good accuracy (accuracy value of 0.74±0.1). However, the best accuracy was obtained using the best 20 features from feature importance using SVM (0.78±0.1). Moreover, adding non-molecular features shows a great impact on mutual information selected features in this prediction.

Outbreak of COVID-19 among children and young adults in a cancer centre daycare unit.

Nosocomial transmission of COVID-19 among immunocompromised hosts can have a serious impact on COVID-19 severity, underlying disease progression and SARS-CoV-2 transmission to other patients and healthcare workers within hospitals. We experienced a nosocomial outbreak of COVID-19 in the setting of a daycare unit for paediatric and young adult cancer patients. Between 9 and 18 November 2020, 473 individuals (181 patients, 247 caregivers/siblings and 45 staff members) were exposed to the index case, who was a nursing staff. Among them, three patients and four caregivers were infected. Two 5-year-old cancer patients with COVID-19 were not severely ill, but a 25-year-old cancer patient showed prolonged shedding of SARS-CoV-2 RNA for at least 12 weeks, which probably infected his mother at home approximately 7-8 weeks after the initial diagnosis. Except for this case, no secondary transmission was observed from the confirmed cases in either the hospital or the community. To conclude, in the day care setting of immunocompromised children and young adults, the rate of in-hospital transmission of SARS-CoV-2 was 1.6% when applying the stringent policy of infection prevention and control, including universal mask application and rapid and extensive contact investigation. Severely immunocompromised children/young adults with COVID-19 would have to be carefully managed after the mandatory isolation period while keeping the possibility of prolonged shedding of live virus in mind.

Yearlong COVID-19 Infection Reveals Within-Host Evolution of SARS-CoV-2 in a Patient With B-Cell Depletion.

B-cell–depleting therapies may lead to prolonged disease and viral shedding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this viral persistence raises concern for viral evolution. We report sequencing of early and late samples from a 335-day infection in an immunocompromised patient. The virus accumulated a unique deletion in the amino‐terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts.

Prolonged Viral Shedding in Vertically Acquired SARS-CoV-2 Infection in Preterm Infants–Shedding Versus Infectivity

The reported median duration of viral shedding after infection with SARS-CoV2 is between 12 and 20 days. It is now established that infected individuals can continue to shed viral ribonucleic acid (RNA) without shedding live virus. This has implications for quarantine and infection control practices. COVID in the acute phase seems to be milder in children, and the duration of viral RNA shedding is shorter in children compared to adults. SARS-CoV-2 infections in the newborn period is rare. Little is known about the duration of viral shedding in preterm infants with vertically acquired SARS-CoV-2. 3 of the 4 preterm infants cared for at our center had prolonged shedding up to 34 days with live viral shedding not seen beyond the second week when tested in 3 of them.

High-Fat High-Sugar Diet-Induced Changes in the Lipid Metabolism Are Associated with Mildly Increased COVID-19 Severity and Delayed Recovery in the Syrian Hamster.

Pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of COVID-19. Chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a Western Diet. For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome. We observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, and edema, delayed viral clearance and functional lung recovery, and prolonged viral shedding. This was accompanied by an altered, but not significantly different, systemic IL-10 and IL-6 profile, as well as a dysregulated serum lipid response dominated by polyunsaturated fatty acid-containing phosphatidylethanolamine, partially recapitulating cytokine and lipid responses associated with severe human COVID-19. Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19.

278. Immunocompromised Patients with Prolonged Viral Shedding of SARS-COV-2

BackgroundMost individuals diagnosed with mild to moderate COVID-19 are no longer infectious after day 10 of symptom onset and those with severe or critical illness from COVID are typically not infection after day 20 day of symptom onset. Recovered persons can continue to test positive for SARS-CoV-2 by PCR via detection of non-viable RNA in nasopharyngeal specimens for up to three months (or longer) after illness onset. It is also know known that severely immunocompromised patients may produce replication-competent virus greater than 20 days from symptom onset and may require, per CDC recommendations, “additional testing and consultation with infectious diseases specialists and infection control experts”. We aim to discuss four case studies of severely immunocompromised patients who exhibited signs of persistent COVID-19 infection of COVID and how we managed transmission-based precautions in our hospital through sequencing and evaluation of cycle thresholds (CT) values and subgenomic RNA detection. MethodsResidual nasopharyngeal (NP) samples were collected on patients exhibiting persistent COVID like symptoms. These samples underwent N gene and N gene subgenomic RNA (sgRNA) real-time reverse transcription polymerase chain reaction (rRT-PCR) testing. ResultsAnalysis of longitudinal SARS-CoV-2 sequence data demonstrated within-patient virus evolution, including mutations in the receptor binding domain and deletions in the N-terminal domain of the spike protein, which have been implicated in antibody escape. See Figures 1 and 2. Figure 1. Timelines of Identified Patients 1 and 2 Patient 1: 46-year-old woman with recently diagnosed stage IV diffuse large B-cell lymphoma for which she was treated with 2 cycles of R-CHOP. Patient 2: 38-year-old woman with history of myelodysplastic syndrome, peripheral blood stem cell transplant with chronic graft versus host disease of the GI tract, skin, and eyes as well as CMV enteritis, and she was maintained on rituximab, mycophenolate mofetil, prednisone, and monthly IVIG without recent changes to her immunosuppression.Figure 2. Timeline of Identified Patients 3 and 4 Patient 3: 44 year-old man with prior history of thymoma s/p thymectomy Patient 4: 46 year-old man who was initially diagnosed with marginal zone lymphoma approximately 2.5 years ago. He was initially treated with bendamustine and rituximab and achieved remission. He was then continued on maintenance rituximab without significant complications for a planned two years.ConclusionDifferentiating between prolonged viral shedding of non-infectious RNA and persistent replicating viable virus can be difficult to determine without full evaluation of a patient’s clinical picture and timeline. Consultation between laboratory, infectious diseases, and infection prevention experts to provide appropriate level of guidance for precautions and treatment may be warranted. Testing by PCR and analysis of CT values may provide key findings of viral replication in immunocompromised hosts, indicating the need for evaluation of additional treatment and maintaining isolation status in healthcare settings.Disclosures All Authors: No reported disclosures

Administration of HeberFERON in Patients with Persistent Oropharyngeal SARS-CoV-2 Wuhan/D614G Strain Viral Shedding

Study background: HeberFERON accelerates SARS-CoV-2 clearance in COVID-19 cases. Considering this we evaluated the employment of HeberFERON in patients with more than 14 days of viral shedding. Methods: This is a case series study of mild or moderate ill patients with laboratory-confirmed SARS-CoV-2 from one hospital in Havana, Cuba. We evaluated the effect and safety of HeberFERON in patients previously treated with Heberon Apha R that resulted with prolonged viral shedding. All patients received lopinavir-ritonavir 200/50 mg every 12 h and chloroquine 250 mg every 12 h. The primary endpoint was the time to negativization of viral RNA in patients with persistent viral shedding. The protocol was approved by the Ethics Committee of the Luis Diaz Soto Hospital. Results: The characteristics of the individuals included the age ranged from 19-87 years with a mean of 40 years, (Study and Control I groups), while in the Control group II the mean age was 43.8 years. Leukocytes, platelets, neutrophils, and eosinophils, show a significantly lower counts in the groups with viral persistence. Under IFN treatment the median viral shedding duration from diagnosis were 21 days and 19 days in Study group and Control group II, respectively. The Control group I showed a median viral shedding of 11 days (log-rank p = 0.000). Significant longer median viral negativization time (19 days) of symptomatic than asymptomatic patients (11 days, Long-rank p = 0.004), was observed. In patients under Heberon Alpha R treatment that resulted persistent for viral presence, the median time to viral negativization was 7 days for the period of administration of HeberFERON. Being symptomatic at diagnosis was significantly associated with viral persistence. The HeberFERON showed an adequate safety profile. Conclusion: HeberFERON showed a safe and rapid negativization of patients with viral persistence, achieving negativization in more than 50% of patients in 7 days.

Prolonged viral shedding of SARS-CoV-2 and related factors in symptomatic COVID-19 patients: a prospective study

BackgroundThe temporal relationship between SARS-CoV-2 and antibody production and clinical progression remained obscure. The aim of this study was to describe the viral kinetics of symptomatic patients with SARS-CoV-2 infection and identify factors that might contribute to prolonged viral shedding.MethodsSymptomatic COVID-19 patients were enrolled in two hospitals in Wuhan, China, from whom the respiratory samples were collected and measured for viral loads consecutively by reverse transcriptase quantitative PCR (RT-qPCR) assay. The viral shedding pattern was delineated in relate to the epidemiologic and clinical information.ResultsTotally 2726 respiratory samples collected from 703 patients were quantified. The SARS-CoV-2 viral loads were at the highest level during the initial stage after symptom onset, which subsequently declined with time. The median time to SARS-CoV-2 negativity of nasopharyngeal test was 28 days, significantly longer in patients with older age (> 60 years old), female gender and those having longer interval from symptom onset to hospital admission (> 10 days). The multivariate Cox regression model revealed significant effect from older age (HR 0.73, 95% CI 0.55–0.96), female gender (HR 0.72, 95% CI 0.55–0.96) and longer interval from symptom onset to admission (HR 0.44, 95% CI 0.33–0.59) on longer time to SARS-CoV-2 negativity. The IgM antibody titer was significantly higher in the low viral loads group at 41–60 days after symptom onset. At the population level, the average viral loads were higher in early than in late outbreak periods.ConclusionsThe prolonged viral shedding of SARS-CoV-2 was observed in COVID-19 patients, particularly in older, female and those with longer interval from symptom onset to admission.

Emerging SARS-CoV-2 variants can potentially break set epidemiological barriers in COVID-19.

Young age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS‐CoV‐2 variants have key mutations that can induce significant changes in the virus‐host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor‐binding domain (RBD) of the viral spike protein with the angiotensin‐converting enzyme 2 (ACE2) receptor in the host‐cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host‐cell entry and the replication of the virus. The putative changes in the virus–host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS‐CoV‐2 infection and the disease outcomes are known to be influenced by host‐cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry‐receptor and the associated proteases, can have more efficient host‐cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue‐injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine‐acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.

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

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.

Screening of Asymptomatic Healthcare Workers for SARS-COV-2 for Occult Infections: A Cross-Sectional Study.

IntroductionThe SARS-CoV-2 illness (COVID-19) has spread around the world, primarily through person-to-person transmission, and is a serious public health concern. Based on the severity of illness symptoms, SARS-CoV-2 infection can be classified as either apparent or occult. To date, real-time reverse transcription polymerase chain reaction (RT-PCR) on respiratory specimens, particularly nasopharyngeal and oropharyngeal swabs, or nasopharyngeal wash or aspirate, has been the gold standard for the identification of COVID-19. A negative RT-PCR does not necessarily rule out SARS-CoV-2 infection. Occult COVID-19 infections could least be identified with RT-PCR.Aims and objectivesTo assess the prevalence of possible occult COVID-19 infection in healthcare personnel by RT-PCR and serology testing for SARS-CoV-2 virus.MethodsA cross-sectional study was conducted on health care workers at a tertiary care hospital in South India during the period from October 2020 to January 2021. None of the study participants were vaccinated against COVID-19 during the study period. Nasopharyngeal swabs collected for RT-PCR were tested using Cobas 480 platform (Roche, Basel, Switzerland). Peripheral blood venous sampling was performed to collect EDTA (ethylenediaminetetraacetic acid) and plain samples. SARS-CoV-2 IgG antibodies against spike proteins were estimated using ECI Vitros platform (Ortho Clinical Diagnostics, Raritan, USA).ResultsThe mean age of study participants was 34.78 years (SD±9.51) with an age range of 19-69 years. The study participants were stratified into age groups of 19-25 years, 26-40 years, 41-60 years, and above 60 years, gender, ABO and Rh blood groups, and occupational and further based on their area of work as Covid and Non-Covid for the purpose of statistical analysis. Total 190 samples from healthcare workers (HCWs) were tested for RT-PCR using nasopharyngeal swabs collected at the time of enrolment into the study, and all the 190 samples tested negative for RT-PCR. Among 190 HCW samples screened for SARS-CoV-2-IgG antibodies, 48 (25.3%) were found reactive for IgG antibodies while 142 (74.7%) were found non-reactive.ConclusionOur study findings suggested that using RT-PCR testing, which may only identify those with a prolonged viral shedding period and minimum viral loads, the proportion of asymptomatic/occult infections could be underestimated.

Serologic Responses Following Sars-Cov-2 Vaccination and Factors Influencing It in Patients with Hematological Malignant and Non-Malignant Diseases - a Prospective Multicentric Study

BackgroundPatients with hematologic malignancy have a higher risk of death from COVID-19 compared to the general population. A blunted immune response from both the underlying disease and applied treatment may contribute to development of more severe forms of COVID-19, absence of seroconversion, prolonged viral shedding, and might also impair humoral vaccine response. Factors influencing efficacy of SARS-CoV-2 vaccines in this patient population are still insufficiently explored.MethodsWe prospectively enrolled 143 patients with malignant or non-malignant hematologic diseases from University Hospital Centre Zagreb vaccinated between January and June 2021 with either mRNA-1273 (Moderna), BNT162b2 mRNA (Pfizer-BioNTech), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines.A qualitative assay against SARS-CoV-2 nucleocapsid antigen was used to detect prior infection; these patients (n=23) were excluded from the final analysis. Humoral response following vaccination was monitored using serological immunoassay registered for quantitative measurement of serum anti-SARS-CoV-2 RDB-spike protein antibodies. Both electrochemiluminescent assays performed by Cobas e801 analyzer (Roche Diagnostics, Mannheim, Germany) detect total antibodies (including IgG). Response was recorded after the first and second doses. A positive response was defined as > 0.8 U/mL. Upper and lower limits of quantification were 0,4 U/mL and 250 U/mL respectively.We reviewed patient records for demographics, underlying hematological diseases, current treatment, the total number of lines of therapy received, IgG levels, application of anti-CD20 monoclonal antibodies (mAbs) and corticosteroids in the last 6 months before vaccination, and subsequent SARS-CoV-2 infection.Inter-group comparisons were performed with Mann-Whitney U, χ 2, or Fisher's exact test as appropriate. ROC curve analysis was used to find optimized cut-off values of numerical variables regarding response to the second dose. P values <0.05 were considered statistically significant. MedCalc statistical software v 20.008 was used for all analyses.ResultsWe evaluated a total of 120 patients who received at least one dose. Patient characteristics are summarized in Table 1. The majority received the Pfizer-BioNTech vaccine (66.7%), followed by Oxford-AstraZeneca (24.2%) and Moderna (9.2%).Data on humoral response after the first dose was available in 66 patients, among whom 20 (33%) achieved response with median specific IgG levels 6.1 U/mL. Response after the second dose was available in 90 patients; 58 (64.4%) achieved response with median specific IgG levels 250 U/mL. The second dose significantly improved response both in terms of achieved response (P=0.031) and specific IgG levels (P<0.001). There were no significant differences in response or specific IgG levels regarding the type of the vaccine (P>0.05). Lower response rates after the second dose were achieved in patients aged >67 years (P<0.001; response in 32.4% vs. 83.9%), with specific diagnosis (P=0.002, driven by response in patients with non-Hodgkin's lymphoma (NHL; response in 29.2% NHL vs. 77.3% non-NHL) and chronic myeloid leukemia (CML; 100% response in CML vs. 61.4% non-CML)), those receiving active treatment (50% vs. 88%; P<0.001), no prior hematopoietic stem cell transplantation (HSCT; 51% vs. 93%; P<0.001) and prior anti-CD20 mAbs therapy (4% vs. 85%; P<0.001). Corticosteroid therapy (>120 mg prednisone equivalent dose) did not influence the response significantly (response in 88.9% vs. 42.1%; P=0.056), and neither did steroid type. Four (3,3%) patients tested positive for SARS-CoV-2 after vaccination, 2 of which had no humoral response, and 2 had received only one dose. Three patients required in-hospital treatment and oxygen supplementation.ConclusionsPatients with hematologic diseases have lower serological response rates to SARS-CoV-2 vaccines than those previously reported in clinical trials. Our results also suggest they benefit from receiving both doses with no significant difference between vaccine types. Those in active treatment, no prior HSCT, diagnosed with NHL, and receiving anti-CD20 mAb seem more likely to be seronegative after receiving both doses. However, the present study did not examine potential confounding effects between these factors and these findings should be elaborated further in larger patient cohorts. [Display omitted] DisclosuresAurer: Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Swixx/BMS: Honoraria; sanofi genzyme: Consultancy, Honoraria; Teva/Pilva: Honoraria; Abbvie: Consultancy, Honoraria; Eusapharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; takeda: Consultancy, Honoraria. Durakovic: Takeda, Novartis, Genyzme: Honoraria.

Operational challenges in the COVID-19 era: Asymptomatic infections and vaccination timing.

The coronavirus disease 2019 (COVID‐19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid testing (NAT) for SARS‐CoV‐2 is unclear, as this result may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of robust outcomes data, transplant professionals at US adult kidney transplant centers were surveyed (February 13, 2021 to April 29, 2021) to determine community practice (N: 92 centers, capturing 41% of centers and 57% of transplants performed). The majority (97%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 32% of centers proceed with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with kidney transplant in patients with positive SARS‐CoV‐2 NAT results due to presumed viral shedding. Furthermore, few centers are requiring COVID‐19 vaccination prior to transplantation at this time.

Viral shedding in asymptomatic versus symptomatic patients with COVID-19

BackgroundAn outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the association between a prolonged viral shedding in patients with COVID-19 and having symptoms. We aimed to study the association between the presence of symptoms and recovery time of COVID-19 confirmed patients.MethodsWe conducted a prospective cohort study of COVID-19 patients admitted to the designated national COVID-19 center in Monastir, Tunisia from March to July 2020. Kaplan-Meier survival curve and Cox proportional hazards regression models were used to assess viral shedding in asymptomatic versus symptomatic patients with COVID-19.ResultsAmong the 264 patients included in the study, symptoms such as anosmia, dry cough, and fatigue were reported by 34.4% (n = 75) of cases. The median time to RNA viral conversion was 24 days (IQR 18-36 days) for symptomatic patients versus 20 days (IQR 16-30 days) for asymptomatic patients. Having symptoms was significantly associated with a prolonged viral shedding (HR 0.600, 95% CI 0.401-0.897) (p = 0.013).ConclusionsOur findings revealed that having symptoms delayed viral clearance among COVID-19 patients. Therefore, symptomatology should be taken into consideration in isolation strategy for infected patients.Key messages Having symptoms was associated with a delay in SARS-CoV-2 RNA clearance.The presence of symptoms should be taken into consideration for patient’s isolation strategy.

Comparison of SARS-CoV-2 RNA clearance between elderly and young patients with COVID-19

BackgroundThe SARS-CoV-2 outbreak in 2020 caused a highly transmissible disease with a significant impact on the elderly. Understanding viral clearance duration of COVID-19 is important to tailor prevention strategies to this vulnerable category. We aimed to investigate the SARS-CoV-2 infection duration and associated factors to prolonged viral clearance among elderly people comparatively to young people.MethodsWe conducted a cohort study of asymptomatic and mild forms of COVID-19 patients admitted to the designated national COVID-19 center in Monastir, Tunisia. Patients included in the study were divided into two cohorts: (elderly group: ≥ 60 years old) and (young group: < 60 years old) and were followed up to their RNA viral conversion. Stratified cox regression was performed to determine associated factors with prolonged viral SARS-CoV-2 RNA clearance in elderly subgroups.ResultsThe study included a total of 289 patients with asymptomatic and mild forms of COVID-19. The median term of viral shedding was 20 days (IQR; 16 - 32 days) for the young group, and 21 days (IQR; 17 - 33 days) for the elderly group. The stratified cox regression showed that Age ≥ 60 was an associated factor to prolonged viral shedding in male sex (HR (Hazard Ratio): 1.91; 95% CI: 1.19 - 3.07) and patients with comorbidities (HR:1.68; 95% CI: 1.02 - 2.75) especially diabetics (HR: 2.06; 95% CI: 1.01 - 4.21).ConclusionsThis study, focused on the factors associated with a prolonged duration of viral RNA clearance in elderly with COVID-19. These Potential factors will help planners to chalk out effective strategies among this vulnerable category.Key messages Old age is associated with a prolonged duration of viral RNA clearance in specific subgroups.Identifying these subgroups is important to know how prioritize preventive strategies in elderly.

Recurrent SARS-CoV-2 RNA positivity and prolonged viral shedding in a patient with COVID-19: a case report

BackgroundThe ongoing coronavirus disease 2019 (COVID-19) global pandemic caused by the SARS-CoV-2 virus remains a major threat to public health. At present, it is recommended that patients with known or suspected COVID-19 undergo quarantine or medical observation for 14 days. However, recurrent SARS-CoV-2 RNA positivity and prolonged viral shedding have been documented in convalescent COVID-19 patients, complicating efforts to control viral spread and ensure patient recovery.Case presentationWe report the case of a patient who experienced two recurrent episodes of SARS-CoV-2 RNA and IgM positivity and viral shedding over 60 days during hospitalization.ConclusionsThis case report demonstrates that relapses of SARS-CoV-2 RNA and IgM positivity may occur even after COVID-19 symptoms have resolved, possibly as a consequence of prolonged viral shedding rather than re-infection.

Prolonged Gut Dysbiosis and Fecal Excretion of Hepatitis A Virus in Patients Infected with Human Immunodeficiency Virus.

Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we aimed to comprehensively observe the amount of virus excreted into the intestinal tract, the changes in the intestinal microbiome, and the level of inflammation during the healing process. We used blood and stool specimens from patients with human immunodeficiency virus who were infected with HAV during the HAV outbreak in Japan in 2018. Moreover, we observed changes in fecal HAV RNA and quantified the plasma cytokine level and gut microbiome by 16S rRNA analysis from clinical onset to at least 6 months after healing. HAV was detected from clinical onset up to a period of more than 150 days. Immediately after infection, many pro-inflammatory cytokines were elicited, and some cytokines showed different behaviors. The intestinal microbiome changed significantly after infection (dysbiosis), and the dysbiosis continued for a long time after healing. These observations suggest that the immunocompromised state is associated with prolonged viral shedding into the intestinal tract and delayed recovery of the intestinal environment.

The epidemiology and examination of clinical outcomes in children with COVID-19: A research overview

COVID- 19 pandemic has affected hundreds of thousands of people worldwide, and so far, accounted for 0.39-12.3% of affected disease population. Even though a large number of studies have reviewed symptoms and characteristics of adults with COVID-19, only some of them have included a smaller number of children.This study aimed a) To examine the epidemiological characteristics of SARS-CoV-2 infection reported in children from published studies b) To outline the signs and symptoms of SARS-CoV-2 infection reported in children from the research studies and c) To provide converging evidence of the clinical outcomes and prognosis of children affected with SARS-CoV-2 infection from reported studies. A literature review was conducted through online sources of data base available in the internet. Studies published from Jan 2020 up to September 2021 were included. The organism causing infection was the novel Corona virus (SARS-CoV-2). In children, almost 0.39-12.3% of the population was affected. A slight predominance of boys vs. girls was noted, but it was not statistically significant. The incubation period ranged from 2-14 days. Nearly 51% of children were presenting with mild disease and nearly 4% were asymptomatic. The children also presented with non-respiratory symptoms, but the exact figures were not available. Multisystem inflammatory response was the most common reported complication. Current findings indicate that children have a lower incidence of the disease, with milder predominance and better prognosis, but prolonged shedding of virus in the nasal and stools sample and being asymptomatic raises a concern of community transmission.

EXCELLENT ALLOGRAFT RECOVERY DESPITE PROLONGED SARS-COV-2 SHEDDING AFTER REDUCTION OF IMMUNOSUPPRESSION IN LUNG TRANSPLANT RECIPIENT

TOPIC: Transplantation TYPE: Medical Student/Resident Case Reports INTRODUCTION: Immunosuppressed lung transplant recipients (LTxRs) are predisposed to severe SARS-CoV-2 disease, impaired virus clearance, and increased mortality. Successful recovery from SARS-CoV-2 infection after reduction of immunosuppression (IS) has been reported in kidney and heart transplant recipients [1,2]. We report a case of favorable allograft outcome after reduction of IS in an LTxR with SARS-CoV-2 pneumonia despite prolonged virus shedding. CASE PRESENTATION: A 58-year-old bilateral LTx recipient (July 2020) with blood type A+ was admitted for a positive SARS-CoV-2 RT-PCR result from a nasal wash on July 31, 2020 (day 1). He exhibited fever, increasing shortness of breath, a productive cough, and bilateral radiographic infiltrates, but normal oxygen saturation on room air and stable pulmonary function tests (FVC and FEV1 at 3.17 and 2.65 liters, respectively). Shortly after hospitalization, his dyspnea and oxygen requirement increased (3 LPM) and inflammatory markers were elevated (nadirs of lymphocyte 2.7 thousand/µL and platelet 158 thousand/µL;peaks of D-dimer 260 ng/mL, CRP 75.2 mg/L, ferritin 219 ng/mL, pro-calcitonin 0.22 ng/mL, and LDH 215 U/L). Imaging favored progression of SARS-CoV-2 pneumonia. DSA against DP1 measured 1350 MFI, and immunoglobulin therapy was started. The patient was managed with intravenous corticosteroid pulse, Remdesivir, and convalescent plasma along with appropriate antibiotic therapy due to additional concern for superimposed infection. On day 8 of illness onset, the patient no longer had clinical symptoms, and he was discharged on room air and steroid taper. On outpatient follow-up, the patients' endurance had increased;PFTs improved (FVC and FEV1 at 3.9 and 3.39 L, respectively);DSAs were reassuring;and radiographic changes had resolved by day 42 (Figure 1: serial chest imaging from illness onset to day 42). Of note, the ImmuKnow result at illness onset was 64 ng/mL, and mycophenolate (MMF) was reduced to 500 mg BID, after which the ImmuKnow result increased to 560 ng/mL. Seroconversion for SARS-CoV-2 IgG was mounted on day 26 (index 1.56), and MMF was resumed to baseline dose of 750 mg BID on day 35. Remarkably, prolonged viral shedding in nasal wash was noted with the first negative RT-PCR for SARS-CoV-2 on day 47. DISCUSSION: Our patient had excellent recovery with intact graft function despite prolonged virus persistence. Although an immunosuppressed state may have predisposed our patient to bacterial superinfection, reduction of MMF possibly augmented the antiviral response. Despite reduced IS, seroconversion and virus clearance may have been impacted. CONCLUSIONS: Immunosuppressed LTxRs with SARS-CoV-2 pneumonia may demonstrate prolonged viral shedding. Reduction in IS may facilitate allograft recovery despite delayed PCR conversion. Isolation measures should be considered due to possible prolonged infectivity. REFERENCE #1: Li F, Cai J, Dong N. First cases of COVID-19 in heart transplantation from China. J Heart Lung Transplant. 2020 May;39(5):496-497. REFERENCE #2: Zhu L, Xu X, Ma K, Yang J, Guan H, Chen S, Chen Z, Chen G. Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am J Transplant. 2020 Jul;20(7):1859-1863. DISCLOSURES: No relevant relationships by Ashwini Arjuna, source=Web Response No relevant relationships by Ross Bremner, source=Admin input No relevant relationships by Ericka Charley, source=Web Response No relevant relationships by Hesham Mohamed, source=Web Response No relevant relationships by Kristine Nally, source=Web Response No relevant relationships by Ashraf Omar, source=Admin input No relevant relationships by Deepika Razia, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=H noraria Speaker/Speaker's Bureau relationship with Grifols Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Shire Please note: $1001 - $5000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Astellas Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria

Prospective Clinical, Virologic, and Immunologic Assessment of COVID-19 in Transplant Recipients.

Several studies have described the clinical features of COVID-19 in solid-organ transplant recipients. However, many have been retrospective or limited to more severe cases (hospitalized) and have not routinely included serial virological sampling (especially in outpatients) and immunologic assessment. Transplant patients diagnosed with COVID-19 based on a respiratory sample PCR were prospectively followed up to 90 d. Patients provided consent for convalescent serum samples and serial nasopharyngeal swabs for SARS-CoV-2 antibody (antinucleoprotein and anti-RBD) and viral load, respectively. In the 161 SOT recipients diagnosed with COVID-19, the spectrum of disease ranged from asymptomatic infection (4.3%) to hospitalization (60.6%), supplemental oxygen requirement (43.1%), mechanical ventilation (22.7%), and death (15.6%). Increasing age (OR, 1.031; 95% CI, 1.001-1.062; P = 0.046) and ≥2 comorbid conditions (OR, 3.690; 95% CI, 1.418-9.615; P = 0.007) were associated with the need for supplemental oxygen. Allograft rejection was uncommon (3.7%) despite immunosuppression modification. Antibody response at ≥14 d postsymptoms onset was present in 90% (anti-RBD) and 76.7% (anti-NP) with waning of anti-NP titers and stability of anti-RBD over time. Median duration of nasopharyngeal positivity was 10.0 d (IQR, 5.5-18.0) and shedding beyond 30 d was observed in 6.7% of patients. The development of antibody did not have an impact on viral shedding. This study demonstrates the spectrum of COVID-19 illness in transplant patients. Risk factors for severe disease are identified. The majority form antibody by 2 wk with differential stability over time. Prolonged viral shedding was observed in a minority of patients. Reduction of immunosuppression was a safe strategy.