Prolonged Viral Shedding Research Articles

Clinical features and management of human monkeypox: a retrospective observational study in the UK

SummaryBackgroundCases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies.MethodsIn this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network.FindingsWe reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22–39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge.InterpretationHuman monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease.FundingNone.

Cumulative SARS-CoV-2 mutations and corresponding changes in immunity in an immunocompromised patient indicate viral evolution within the host

Different scenarios explaining the emergence of novel variants of concern (VOC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported, including their evolution in scarcely monitored populations, in animals as alternative hosts, or in immunocompromised individuals. Here we report SARS-CoV-2 immune escape mutations over a period of seven months in an immunocompromised patient with prolonged viral shedding. Signs of infection, viral shedding and mutation events are periodically analyzed using RT-PCR and next-generation sequencing based on naso-pharyngeal swabs, with the results complemented by immunological diagnostics to determine humoral and T cell immune responses. Throughout the infection course, 17 non-synonymous intra-host mutations are noted, with 15 (88.2%) having been previously described as prominent immune escape mutations (S:E484K, S:D950N, S:P681H, S:N501Y, S:del(9), N:S235F and S:H655Y) in VOCs. The high frequency of these non-synonymous mutations is consistent with multiple events of convergent evolution. Thus, our results suggest that specific mutations in the SARS-CoV-2 genome may represent positions with a fitness advantage, and may serve as targets in future vaccine and therapeutics development for COVID-19.

Combined blockade of TNF-a and IFN-I receptors in experimental RSV infection: analysis of STAT protein modulation

Abstract Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness in young children. Two cytokines key to RSV pathogenesis are tumor necrosis factor (TNF)-a and type-I interferon (IFN-I). Using a dual receptor antibody blockade of IFNAR1 with either TNFR1 or TNFR2, we previously reported that IFN-I and TNF-a synergistically contribute to clinical disease while also controlling peak lung viral replication in RSV-infected Balb/c mice. The objective of the current study was to investigate the possible effect of TNF-a/IFN-I on prolonged viral shedding and to dissect canonical signaling pathways that would likely mediate the above-described activity. We found that viral titer in the lung of all treatment groups was comparable to the RSV control mice at days six and seven post-infection, indicating that lack of these cytokine receptor signaling was not involved in prolonged viral shedding. We then determined expression levels of total lung STAT1, STAT2, STAT3 and their phosphorylated forms as well as IRF1, pIRF3, IRF7, and IRF9 by western blot. Though RSV/IFNAR1, RSV/TNFR1, and RSV/TNFR2 demonstrated variations in protein expression for several of these signaling molecules, none of these proteins were uniquely modulated by the dual receptor blockade. These findings collectively demonstrate that while TNF-a/IFN-I receptor signaling controls peak viral replication in the lung, they have no effect on extended viral shedding and that STAT1, STAT2, and STAT3 signaling appears to be dispensable for the enhanced viral replication observed in the dual receptor blockade treated mice. Supported by grants from AI062885, AI25434, Clinical and Translational Science Award [(NRSA (TL1) Training Core TL1TR001440)],Supported by UTMB McLaughlin Fellowship

Active viral shedding in a vaccinated hospitalized patient infected with the delta variant (B.1.617.2) of SARS-CoV-2 and challenges of de-isolation

In the era of SARS-CoV-2 variants and COVID-19 vaccination, the duration of infectious viral shedding and isolation in post vaccine breakthrough infections is challenging and depends on disease severity. The current study described a case of SARS-CoV-2 Delta variant pneumonia requiring hospitalization. The patient received two doses of BNT162b2 COVID-19 vaccines, and he had positive SARS-CoV-2 viral cultures 12 days post symptom onset. The time between the second dose of vaccine and the breakthrough infection was 6 months. While immunosuppression is a known risk factor for prolonged infectious viral shedding, age and time between vaccination and breakthrough infection are important risk factors that warrant further studies.

Vaginal transmission causes prolonged Zika virus shedding in the vaginal mucosa and delays systemic dissemination.

Zika virus (ZIKV) has emerged as a significant health threat worldwide. Although typically mosquito-borne, recent evidence suggests that ZIKV is also a sexually transmitted virus. While persistent ZIKV infections in male reproductive tissues have been identified, little is understood regarding the outcomes of primary sexual transmission in females. We investigated how the route of infection affects vaginal ZIKV shedding and dissemination. In two mouse models, vaginal infection resulted in prolonged ZIKV shedding in the vaginal mucosa with delayed systemic infection. Furthermore, heightened vaginal inflammation did not influence ZIKV replication or dissemination, in contrast to previous studies of mosquito-borne infection. Thus, vaginal infection significantly alters ZIKV infection kinetics and must be considered when developing novel treatments.

Prolonged viral shedding identified from external splints and intranasal packings in immediately cured COVID-19 patients with nasal fractures: A retrospective study

BackgroundOur aim was to measure and compare prolonged viral shedding (PVS) identified from external splints (ES) and intranasal packings (IP) for isolated nasal fracture (INF) repair in immediately cured asymptomatic vs. mildly symptomatic COVID-19 patients (AS-COVID vs. MS-COVID). MethodsWe designed a retrospective cohort study and enroled a sample of post-AS-COVID and post-MS-COVID patients, whose INF were treated at a German level 1 trauma centre. The primary predictor variable was COVID severity presurgery (AS-COVD vs. MS-COVID). The main outcome variable was PVS detected in ES/IP. Other study variables were separated into demographic, clinical, and operative. Descriptive, bi- and multivariate statistics were computed, and statistical significance was set at P≤ 0.05. ResultsThe study sample comprised 15 INF patients (53.3% females; 46.7% post-AS-COVID) with a mean age of 42.2 ± 22.7 years (range, 18–85). 13.3% ES and 53.3% IP were contaminated with SARS-CoV-2. However, only IP-contamination between the two cohorts reached statistical significance (P= 0.01; odds ratio, 0.02; 95% confidence interval, 0 to 0.47; Pearson's r= 0.73; post hoc power = 87.4%). Multiple linear regression models refuted the associations between PVS and the other parameters (i.e. age, gender, time to treatment, length of hospital stay, lengths of ES/IP placement). ConclusionsDespite a relative low sample size, our findings suggest PVS via endonasal materials removed from cured COVID-19 patients, especially those healed from MS-COVID. This PVS may trigger re-infection and surgical site infections and/or transmission to other humans, and thereby, requires further investigations.

Persistent Subclinical SARS-CoV-2 Isolation After Redo Lung Transplant for COVID-19-Induced Lung Injury

IntroductionLung transplantation (LTx) is lifesaving for patients with irreversible lung injury due to COVID-19; however, all viable virus must be cleared before transplant. Prolonged viral shedding is common, particularly among immunosuppressed patients. Thus, ongoing detection of SARS-CoV-2 RNA may delay transplant and prolong hospitalization. We report a case of an LTx recipient who developed COVID-19-associated lung injury with prolonged viral shedding that persisted following redo LTx.Case ReportA 48-year-old man developed COVID-19 17 months after bilateral LTx. His illness rapidly progressed to hypoxemic respiratory failure requiring bilevel ventilation and prone positioning. He was treated with corticosteroids, remdesevir, convalescent plasma, anticoagulation, and reduced immunosuppression. Tocilizumab was not administered as data supporting its use was unavailable. Despite aggressive therapy, he remained hypoxemic and developed radiographic evidence of pulmonary fibrosis. SARS-CoV-2 was persistently isolated between November 2020 and April 2021; the PCR cycle threshold in March 2021 was 32, indicating a low level of viral RNA. There was no evidence of antibodies to SARS-CoV-2. Finally, after 2 negative nasopharyngeal swabs in April, he underwent redo bilateral LTx in May 2021, 163 days after his initial diagnosis. Postoperative critical illness myopathy required prolonged mechanical ventilation, nutrition via a feeding tube, and 19 days at an acute rehabilitation center. Routine surveillance bronchoscopy 40 days after retransplant revealed SARS-CoV-2 in bronchoalveolar lavage fluid and again in a nasal wash sample. He had no COVID-19 symptoms at the time of viral isolation, and inflammatory markers were normal. He was empirically treated with casirivimab and imdevimab, with resolution of SARS-CoV-2 isolation 8 days later.SummaryProlonged viral shedding is common in immunocompromised patients with COVID-19; however, ongoing viral isolation is not a reliable indicator of active viral replication and transmissibility. Our patient had persistent SARS-CoV-2 isolation after redo LTx with no evidence of COVID-19 or allograft injury. Thus, persistent viral shedding alone may not be an absolute contraindication to LTx and additional factors such as PCR cycle threshold and time from original infection should be considered.

The first study on confirmation and risk factors of acute and chronic canine distemper in stray dogs in Wasit Province, Iraq, using enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction.

Background and Aim:In Iraq, stray dogs represent a critical population of free-roaming animals, which probably play a role in the transmission of different infections to other animals. Canine distemper is one of the most growing viral threats to carnivores in many countries worldwide, including Iraq. Therefore, this study was aimed to diagnose the disease using serological and molecular assay and the role of risk factors in the spreading infection.Materials and Methods:In all, 158 venous blood samples were collected randomly from stray dogs in rural and sub-urban areas of Iraq from May 2019 to December 2020. The samples were examined serologically using two enzyme-linked immunosorbent assay (ELISA) kits, immunoglobulin G (IgG) and immunoglobulin M (IgM), and molecularly by reverse transcription-polymerase chain reaction (RT-PCR) to detect and confirm chronic and acute infections. To determine the association between infection and various risk factors, the study animals were divided according to their locations, sexes, and ages. The age groups were ≤8 months (puppy), 1-3 years (young), and ≥3 years (old/mature).Results:ELISA result shows that 6.96% and 19.62% of dogs were seropositive for acute and chronic distemper, respectively. The titer of chronic infections (0.421±0.027) was significantly higher (p≤0.025) than that of acute canine distemper (0.337±0.016). On RT-PCR, 8.86% of dogs were found positive for distemper. Using RT-PCR as the gold standard, the sensitivity and specificity of the IgM ELISA kit were 75% and 98.63%, respectively, whereas the positive and negative predictivity were 81.82% and 97.96%, respectively. A significant variation (p<0.05) was observed in the distribution of positive findings among the different epidemiological risk factors. Compared with rural areas, positivity was significantly higher (p<0.05) in sub-urban areas on IgM (26.92%) and IgG (64.15%) ELISA and RT-PCR (34.62%). On IgM ELISA and RT-PCR, no significant differences (p>0.05) were found among the three age groups; however, positivity was significantly higher (p≤0.048) in the ≥3 years group (22.73%) on IgG ELISA. Furthermore, only IgG ELISA showed a significantly higher (p≤0.032) positivity rate in female dogs (25.23%) than in male dogs (7.84%).Conclusion:To the best of our knowledge, this is the first Iraqi study to demonstrate acute and chronic canine distemper in stray dogs, suggesting that the prolonged shedding of virus from positive dogs is a critical point in the epidemiology of the disease. Additional studies in dogs or other carnivores are required to establish baseline data on the prevalence of the disease in Iraq.

Persistent Viral Detection After Resolution of COVID-19 in Lung Transplant Recipients

IntroductionPersistent detection of SARS-CoV-2 viral particles has been seen in the absence of symptoms in other solid organ transplant recipients. We report this unique phenomenon in lung transplant (LTx) recipients.Case ReportWe present the following cases of prolonged viral shedding in 3 LTx recipients: Patient A - 68-year-old female, bilateral LTx recipient for COPD (02/2020), Patient B - 65-year-old male, bilateral LTx recipient for IPF (07/2020), and Patient C - 64-year-old female, bilateral LTx recipient for COPD (08/2020). There were no major intraoperative complications, and the maintenance immunosuppression regimen was the same across patients. Patient A contracted COVID-19 at our center 10 months after transplant, reporting upper respiratory infection symptoms, after initially presenting with persistent headaches and diagnosed with posterior reversible encephalopathy syndrome. Patients B and C presented to clinic with myalgias and mild dyspnea at one and five months after transplant, respectively. SARS-CoV-2 was detected by RT-PCR of nasopharyngeal specimens in all patients. Chest CT demonstrated typical findings of COVID-19 pneumonia in all patients. Patients A and C received remdesivir and belatacept and were discharged home on days 5 and 7, respectively; Patient B received remdesivir and convalescent plasma and was discharged home on day 8. All were in stable clinical condition on room air. All 3 patients had persistently positive nasopharyngeal swab samples up to four weeks after hospitalization, despite absence of symptoms. We did not augment immunosuppression in these patients. Imaging findings during and after the infectious course are shown in Figure 1. Patient C has persistent lower lobe radiographic changes after COVID-19.SummaryLTx recipients may exhibit prolonged viral shedding up to at least 1 month despite resolution of symptoms. Well-established cohort studies are needed to elucidate the full duration of viral shedding in this group.

Clinical and Virological Characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta) Variant: A Prospective Cohort Study.

BackgroundData on the clinical and virological characteristics of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. This prospective cohort study compared the characteristics of the Delta variant to other variants.MethodsAdult patients with mild coronavirus disease 2019 (COVID-19) who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcription polymerase chain reaction (PCR). Cell cultures were performed on saliva samples with positive genomic RNA results.ResultsA total of 141 patients (Delta group, n = 108 [77%]; non-Delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the Delta group than in the non-Delta group (52% vs 27%, P = .03). Total symptom scores were significantly higher in the Delta group between days 3 and 10 after symptom onset. Initial genomic RNA titers were similar between the 2 groups; however, during the late course of disease, genomic RNA titers were higher in the Delta group. Negative conversion of subgenomic RNA was slower in the Delta group (median 9 vs 5 days; P < .001). The duration of viral shedding in terms of positive viral culture was also longer in the Delta group (median 5 vs 3 days; P = .002).ConclusionsCOVID-19 patients infected with the Delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-Delta variants.

Delayed Clearance of Viral RNA in Sputum for Severity COVID-19 Patients with Initial High Viral Load.

AimTo analyze the possible risk factors of delayed virus clearance in hospitalized patients with coronavirus disease 2019 (COVID-19).MethodsRetrospective analysis of patients with COVID-19 admitted to the isolation wards from our hospital from 19th Jan 2020 to 18th March 2020. We were collected patient’s data including demographic, epidemiologic, and clinical information, as well as laboratory and radiologic findings. The possible confounding risk factors for prolonged viral RNA shedding of COVID-19 during hospitalization were explored by univariate analysis and any variables with a p value less than 0.05 after univariate analysis were included in a subsequent multivariate logistic regression model analysis.ResultsThe 104 patients included 30 mild patients and 74 severe or critically ill patients. The median duration of viral RNA positivity in sputum was 11 days, and the longest duration of viral RNA positivity was 49 days after admission. Multivariate analysis shown that the used with darunavir/cobicistat treatment (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 1.25–14.42, p = 0.020), duration of fever (OR: 1.15, 95% CI: 1.03–1.30, p = 0.015) and time to radiological improvement (OR: 1.14, 95% CI: 1.01–1.30, p = 0.033) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Then adjusted in the multivariate binary logistic regression analysis model in severe COVID-19 and found that critical COVID-19 patients (OR: 13.25, 95% CI: 1.45–12.07, p = 0.022), lower virus cycle threshold (CT) values of RT-PCR (OR: 0.96, 95% CI: 0.93–0.99, p = 0.004) and used with darunavir/cobicistat treatment (OR: 8.44, 95% CI: 2.21–32.28, p = 0.022) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients.ConcludeClearance of viral RNA in sputum was delayed in severe COVID-19 patients, especially with lower virus CT value. And antivirals with darunavir/cobicistat has little advantage in eliminating SARS-CoV-2.

SARS-CoV-2 infection in the immediate post-transplant period: A report of five kidney transplant recipients

Introduction: The severe acute respiratory syndrome coronavirus 2 pandemic caused a negative impact on transplantation worldwide. One of the complexities is the management of the immunosuppression and anti-viral medication in transplant recipients. Herein we describe our experience managing five patients with coronavirus disease 2019 (COVID-19) immediately after kidney transplant. Description: we describe a series of five transplant recipients. Two were submitted to a low immunological risk induction immunosuppression: one developed severe disease, the other developed critical disease. The remaining three were submitted to a high immunologic risk immunosuppression: one developed mild disease, but approximately two months after diagnosis developed moderate COVID-19; another developed severe COVID-19; the remaining patient developed critical illness and perished. Both patients with critical COVID-19 developed bacterial and fungal superinfections in the Intensive Care Unit. All eligible patients were submitted to remdesivir and dexamethasone. The anti-metabolite was reduced or suspended. Despite worsening kidney function during the acute phase, kidney replacement therapy was only needed in one patient and the average serum creatinine at the time of discharge was lower that the pre-COVID-19 nadir. Discussion: There is still no definitive answer on whether solid organ transplant recipients carry a higher risk for morbimortality. Risk factors for the general population can also affect their outcome. The prolonged viral shedding in recipients may explain the irregular evolution of the patient who developed COVID-19 months after the initial diagnosis. The reduction of immunosuppression can be problematic in early post-transplant, but no apparent signs of rejection were noted. Literature addressing this specific context is scarce and studies are needed to clarify the optimal management of these patients.

Duration of viral clearance and factors associated with viral clearance among COVID-19 patients admitted in a tertiary care center in north Kerala

Background: COVID-19 pandemic has afflicted the global health scenario for nearly two years. There are limited studies regarding potential predictors of viral clearance in COVID-19 patients. These predictors can aid in identifying patients with prolonged viral shedding and initiate further research for interpreting host immune response to COVID-19. Viral clearance data in treated patients may shed light on the relationship between the host immune system and SARS-CoV-2. Objective of this study was to estimate viral clearance and study the factors associated with viral clearance in COVID-19 patients.Methods: A descriptive study was conducted among 588 COVID-19 patients admitted during the 6-month study period. Data was collected from case records and analyzed using SPSS version 21. Results expressed as mean, standard deviation, frequencies, and percentages. Pearson Chi square test used to find association between viral clearance and associated factors.Results: Among the 588 COVID-19 patients, majority (54%) were females. 21-30 years age-group had the maximum proportion (29.2%) of cases. Most common comorbidity reported was diabetes mellitus. The mean duration of viral clearance (VC) was 8.16±2.1 days. Delayed viral clearance was present in 21% of the study population. There was statistically significant association between male gender and delayed viral clearance. ICU admission and delayed VC also had significant association, with 95% of those admitted in ICU having delayed VC. Male gender could be a confounding variable for association between ICU admission and delayed viral clearance.Conclusions: One fifth of the study population had delayed viral clearance. Delayed viral clearance is associated with male gender and ICU admission.

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity.

Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4+ T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients.

Prolonged SARS-CoV-2 infection following rituximab treatment: clinical course and response to therapeutic interventions correlated with quantitative viral cultures and cycle threshold values

BackgroundDetection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is completed through reverse transcriptase-PCR (RT-PCR) from either oropharyngeal or nasopharyngeal swabs, critically important for diagnostics but also from an infection control lens. Recent studies have suggested that COVID-19 patients can demonstrate prolonged viral shedding with immunosuppression as a key risk factor.Case presentationWe present a case of an immunocompromised patient with SARS-CoV-2 infection demonstrating prolonged infectious viral shedding for 189 days with virus cultivability and clinical relapse with an identical strain based on whole genome sequencing, requiring a multi-modal therapeutic approach. We correlated clinical parameters, PCR cycle thresholds and viral culture until eventual resolution.ConclusionsWe successfully demonstrate resolution of viral shedding, administration of COVID-19 vaccination and maintenance of viral clearance. This case highlights implications in the immunosuppressed patient towards infection prevention and control that should consider those with prolonged viral shedding and may require ancillary testing to fully elucidate viral activity. Furthermore, this case raises several stimulating questions around complex COVID-19 patients around the role of steroids, effect of antiviral therapies in absence of B-cells, role for vaccination and the requirement of a multi-modal approach to eventually have successful clearance of the virus.

Coronavirus Disease-19 Testing Strategies for Patients and Health Care Workers to Improve Workplace Safety.

Tests to detect active viral infection and related immune response in the staff and patients attending health care facilities effectively identified positive cases presenting with or without symptoms of coronavirus disease (COVID)-19. Subsequent home isolation of these contagious cases helped curb the chance of the spread of infection at the workplace. Furthermore, serologic tests conducted postvaccination facilitated the detection of individuals with poor immune response following active immunization that would likely require further safety measures to protect themselves from contracting the infection in health care facilities.

High prevalence of SARS-CoV-2 detection and prolonged viral shedding in stools: A systematic review and cohort study

ObjectivesTo: 1. Describe the frequency of viral RNA detection in stools in a cohort of patients infected with SARS-CoV-2, and 2. Perform a systematic review to assess the clearance time in stools of SARS-CoV-2. MethodsWe conducted a prospective cohort study in two centers between March and May 2020. We included SARS-CoV-2 infected patients of any age and severity. We collected seriated nasopharyngeal swabs and stool samples to detect SARS-CoV-2. After, we performed a systematic review of the prevalence and clearance of SARS-CoV-2 in stools (PROSPERO-ID: CRD42020192490). We estimated prevalence using a random-effects model. We assessed clearance time by using Kaplan–Meier curves. ResultsWe included 32 patients; mean age was 43.7±17.7 years, 43.8% were female, and 40.6% reported gastrointestinal symptoms. Twenty-five percent (8/32) of patients had detectable viral RNA in stools. The median clearance time in stools of the cohort was 11[10–15] days. Systematic review included 30 studies (1392 patients) with stool samples. Six studies were performed in children and 55% were male. The pooled prevalence of viral detection in stools was 34.6% (twenty-four studies, 1393 patients; 95%CI:25.4–45.1); heterogeneity was high (I2:91.2%, Q:208.6; p≤0.001). A meta-regression demonstrates an association between female-gender and lower presence in stools (p=0.004). The median clearance time in stools was 22 days (nineteen studies, 140 patients; 95%CI:19–25). After 34 days, 19.9% (95%CI:11.3–29.7) of patients have a persistent detection in stools. ConclusionsDetection of SARS-CoV-2 in stools is a frequent finding. The clearance of SARS-CoV-2 in stools is prolonged and it takes longer than nasopharyngeal secretions.

Case of Prolonged Viral Shedding: Chronic, Intermittan COVID-19?

COVID-19 is a pandemic that has been affecting the entire world and has caused the death of approximately 2.8 million people. Although the duration of viral shedding varies, an average of 7-10 days is accepted. It is still unclear whether prolonged viral shedding means prolonged contagious period and whether COVID-19 will become chronic or not. This article presents a case with hematological malignancy (lymphoma) with the longest polymerase chain reaction positivity that we could find in the literature (110 days in total).

Influence of Fasting Plasma Glucose Level on Admission of COVID-19 Patients: A Retrospective Study.

Background The coronavirus disease 2019 (COVID-19) is a serious global health threat and has spread dramatically worldwide. Prolonged viral shedding is associated with a more severe disease course and inflammatory reaction. Blood glucose levels were significantly associated with an increased hazard ratio (HR) for poor outcomes in COVID-19 patients. Objective Previous studies focused primarily on the relationship between blood glucose and mortality or severe outcomes, but there were few research studies on the relationship between fasting plasma glucose (FPG) and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positive status. To explore the relationship between FPG levels and prolonged duration of SARS-CoV-2 viral positivity, the clinical data of COVID-19 patients were analyzed. Method In this retrospective study, 99 cases of COVID-19 patients in Beijing Ditan Hospital were recruited, and their clinical and laboratory findings at admission were collected and analyzed. Furthermore, the risk factors for prolonged duration of SARS-CoV-2 RNA shedding were identified, and the relationship between FPG levels and the prolonged presence of SARS-CoV-2 RNA was evaluated. Result We found that elevated FPG levels were correlated with longer duration of SARS-CoV-2 RNA positivity, classification of COVID-19, imaging changes of chest CT, inflammation-related biomarkers, and CD8+ T cell number in COVID-19 patients. In a logistic regression model, after adjusting for gender and age, COVID-19 patients with elevated FPG were more likely to had longer duration of SARS-CoV-2 RNA positivity than those with normal FPG levels (OR 3.053 [95% CI 1.343, 6.936]). Conclusion Higher FPG levels (≥6.1 mmol/l) at admission was an independent predictor for prolonged SARS-CoV-2 shedding, regardless of a known history of diabetes. It suggests that intensive monitoring and control of blood glucose are important for all COVID-19 patients.

Evaluation of In-Hospital Cluster of COVID-19 Associated With a Patient With Prolonged Viral Shedding Using Whole-Genome Sequencing.

BackgroundPatients with hematologic malignancies may produce replication-competent virus beyond 20 days of SARS-CoV-2 infection. However, data regarding the transmission of SARS-CoV-2 from patients with prolonged viral shedding is limited.MethodsIn May 2022, four additional cases of COVID-19 were reported in a hematologic ward at a tertiary care hospital in South Korea, after an 8-week isolation of a patient with prolonged viral shedding. We performed whole-genome sequencing (WGS) of SARS-CoV-2 to evaluate the possibility of post-isolation transmission from this prolonged viral shedding.ResultsA patient (case 1) with acute myeloid leukemia was released from isolation 54 days after the diagnosis of COVID-19 based on rising Ct value of up to 29.3, and moved to a six-patient room. On days 10 and 11 post-isolation, his doctor (case 2) and 2 patients who were his roommates (case 3, 4) had positive SARS-CoV-2 PCR results. Additionally, 16 days post-isolation, another patient (case 5) in a remote room had positive SARS-CoV-2 PCR result. All the three patients were hospitalized for ≥ 14 days when they were diagnosed with SARS-CoV-2 infection. Except for case 3, the remaining 4 cases were available for WGS, which revealed that case 1 exhibited a 7 nucleotides difference in comparison to cases 4 and 5 and case 2 displayed a 20 nucleotides difference compared with case 1, while sequences of cases 4 and 5 were identical.ConclusionsDespite the possibility of transmission from the patient with prolonged viral shedding, no evidence of the transmission of SARS-CoV-2 from the patient with prolonged positive RT-PCR using WGS was found.