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1.
Tissue Engineering - Part A ; 28:228-229, 2022.
Article in English | EMBASE | ID: covidwho-2062829

ABSTRACT

Purpose/Objectives: Bioprinted models of lung tissue are in high demand but in short supply, particularly for addressing the research needs in response to COVID-19 pandemic. The lung is arguably one of the most complex organs in the body, with a multiscale cytoarchitectural organization serving its multiple functions. In particular, the cellular structure of the alveolar sacs poses a big challenge to extrusion bioprinting, which is more adept at capturing the external shape of biological objects than their cell-level details.Methodology: Recently, we proposed a constructive compromise, attainable by bioprinting of equivalent 3D constructs derived from individual (such as 'precision cut lung slices') or stackable (serial histological sections) anatomic images. The advantage of this approach is that in these images, which can be obtained either from regular histology, or confocal fluorescence or electron microscopy (EM), is already incorporated a wealth of structural information. This can be first transferred to '2.5 dimensional' models (by giving them a finite thickness), and then these can be printed layer-by-layer and stacked as tissue-equivalent 3D volumes. Here we illustrate this proposed workflow with 3D printed human lung sections, and with a lung fragment reconstituted from serial sections, while also simulating the infection with SARS-CoV-2 virus in the same constructs by an agent-based modeling approach.Results: As proof of concept, we processed a human lung histological section in CAD, converted it as .stl file and then 3D printed it using as materials both polycaprolactone (by fused filament fabrication), and by the FRESH method using alginate as hydrogel bioink. Similarly, we extracted from a serial EM stack an image selection which was imported in CAD as well and printed as a self-standing object by photolithography. Here we also report the re-purposing of a simulation program of SARS-CoV-2 infection created on the CompuCell 3D (CC3D) platform, to analyze the propagation of infection in cellular patterns derived from the same histological and ultrastructural sections of human lungs. Using it, we explored the spatial distribution and kinetics of several cell classes (infected, virus shedding, apoptotic), the associated viral and cytokine fields, as well as the impact of the presence of generic inflammatory cells, in comparison with the comparable situations when the cell distribution was a uniform epithelial monolayer. We noted a good reproducibility of these simulations, in spite of the section-characteristic cell distribution patterns, and of the initial locations ('seeding') of the viral infection. In addition, we reconstructed thicker virtual tissue slices from multiple single-cell layers for the study of their viral infection as well.Conclusion/Significance: In conclusion, while more sophisticated methods to capture the tissue structure in 3D constructs certainly exist, the extrusion bioprinting is shown here to be capable to offer a simpler, more practical, and more affordable alternative. We also demonstrated how computational simulations on the same images as used in bioprinting, can be used as a useful heuristic instrument to anticipate the results of the interaction of viruses with bioprinted structures that are more complex than cellular monolayers.

2.
Swiss Medical Weekly ; 152:14S, 2022.
Article in English | EMBASE | ID: covidwho-2040956

ABSTRACT

Background: The highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of a vaccine against COVID-19. Methods: In the current study, we evaluated the immunogenicity of a traditional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal administration in a murine model. The candidate vaccine platform, CuMVTT -RBD, has been optimized to incorporate a universal T helper cell epitope derived from tetanus-toxin and is self-adjuvanted with TLR7/8 ligands. Results: CuMVTT-RBD vaccine elicited a strong systemic RBD- and spike- IgG and IgA antibodies of high avidity. Local immune response was assessed and our results demonstrate a strong mucosal antibody and plasma cell production in lung tissue. Furthermore, the induced systemic antibodies could efficiently recognize and neutralize different variants of concern (VOCs) of mutated SARS-CoV-2 RBDs. Conclusion: Our data demonstrate that intranasal administration of CuMVTT-RBD induces a protective systemic and local specific antibody response against SARS-CoV-2 and its VOCs.

3.
GERMS ; 12(2):276-282, 2022.
Article in English | EMBASE | ID: covidwho-2033513

ABSTRACT

The ongoing coronavirus disease-2019 (COVID-19) pandemic can be acknowledged as one of the most significant public health emergencies the world has encountered in the last few decades. The purpose of the current review is to understand the significance of contact tracing and explore the pros and cons of digital contact tracing in ensuring better containment of the COVID-19 outbreaks. A widespread search of published articles pertaining to the topic was done in the PubMed search engine and a total of 46 articles matching the objectives of the present review were identified. However, four articles were discarded because of the non-availability of the free full text, and thus 42 research papers were finally included. Digital contact tracing bridges the gap wherein we aim to expedite the process of contact tracing to identify the potential contacts of the confirmed cases. These applications are designed in such a way that they send a notification on the smartphone of a person, once the user is exposed to one or more confirmed cases of COVID-19. To conclude, in the battle against the COVID-19 infection, the international welfare agencies and national policy makers have been looking forward to the employment of digital technologies to support the ongoing public health measures for contact tracing. The approach of digital contact/proximity tracing should be considered as a supplement to conventional manual tracing. The need of the hour is to take specific measures to improve the inherent design of these apps, their implementation and demonstration of their effectiveness, which in turn will play a part in enhancing their acceptance and usability among the general population.

4.
Journal of Public Health in Africa ; 13:10-11, 2022.
Article in English | EMBASE | ID: covidwho-2006932

ABSTRACT

Introduction/ Background: South Africa recorded its first COVID-19 case on 5 March 2020 and continues to report the largest number of cases in Africa. Determining viral shedding time is crucial in understanding COVID-19 transmission dynamics in South Africa. We aimed to estimate viral shedding time among laboratoryconfirmed COVID-19 cases in South Africa. Methods: We performed a cross-sectional analytic study using COVID-19 data collected in 2020, obtained from the NMCList and DATCOV systems. These platforms report laboratory-confirmed and hospitalized COVID-19 patients, respectively. The study consisted of laboratory-confirmed COVID-19 patients with repeat positive PCR tests (at least two positive PCR test results) and who subsequently tested negative. We defined shedding time as the period from the first positive PCR test to the last positive test prior to a first negative PCR test result. To determine the association between shedding time and predictor variables, multivariate analysis was conducted and a p-value <0.05 was considered statistically significant. Results: We included 2752 cases. About 39.9% (1099/2752) of participants were inpatients and 60.1% (1653/2752) outpatients. The median shedding time was 17 days (range: 1-128). There was no significant difference in shedding time between males (median: 16 days, range: 1-128) and females (median: 17 days, range: 1- 94) and between inpatients (median: 16 days, range 1-108) and outpatients (median: 17 days, range: 1- 128). Individuals aged 0-4 years had the lowest shedding time (median: 14 days, range: 1-72). After adjusting for age, sex and province, shedding time was shorter for admitted cases compared to outpatients (coefficient: -0.14, CI: -0.24 - -0.03, Pvalue: 0.014). Impact: Our results will assist in refining COVID-19 infection control strategies and assist in the interpretation of repeat positive COVID-19 PCR tests over time. These results may also be used in facilitating early treatment and intervention, leading to a decrease in the incidence and mortality due to coronavirus disease. Conclusion: The duration of viral shedding within the population of South Africa varies from 1 to 128 days. Admission status is associated with SARS-CoV-2 shedding time. Our findings indicate that infection control strategies should take into account factors affecting shedding time such as disease severity.

5.
Journal of Public Health in Africa ; 13:10, 2022.
Article in English | EMBASE | ID: covidwho-2006920

ABSTRACT

Introduction/ Background: By August 2021, 6.2 million cases of COVID-19 have been reported in Africa, which has about 70% of the global burden of HIV. The purpose of this study was to assess SARS-CoV-2 viral load in people living with and without HIV. Methods: We screened 2174 ambulatory patients presenting at three primary healthcare facilities and enrolled 106 consenting individuals who tested positive for SARSCoV- 2 primarily during the second wave in Durban, South Africa. Participants were enrolled within three days of SARS-CoV-2 screening and were then followed up at day 7, 14 and 28, and at month 3 and 6 post screening visit. Data on SARS-CoV-2 Ct number, as well as laboratory parameters were collected blinded to HIV status. Results: All 106 participants presented with mild to moderate COVID-19. Thirty of 106 participants were HIV positive;26 (86.5%) were on ART, of which 21 (77.8%) were virally supressed. Their CD4+ T-cell count ranged from 286 to 843 with the median 500 cells/mm3. In the HIV infected cohort, longer viral shedding was associated with having a CD4+ T cell count <500 at enrolment (adjusted hazards ratio: 0.31, 95% confidence interval: 0.12-0.80, p=0.015). We observed no significant differences in the clinical presentation and disease outcomes of HIV infected and HIV uninfected COVID-19 patients. Impact: Considering the implications that prolonged viral shedding could have on emergence of new viral variants and global vaccination efforts, HIV patients failing therapy should be prioritized for current prevention measures. Conclusion: Presence of HIV co-infection did not result in worsened clinical presentation in this cohort. Of note, we identified HIV infection with CD4 counts <500 as a potential driver of prolonged SARS-CoV-2 viral shedding.

6.
Front Microbiol ; 13: 946549, 2022.
Article in English | MEDLINE | ID: covidwho-1993801

ABSTRACT

Chronically immunosuppressed patients infected with SARS-CoV-2 often experience prolonged virus shedding, and may pave the way to the emergence of mutations that render viral variants of concern (VOC) able to escape immune responses induced by natural infection or by vaccination. We report herein a SARS-CoV-2+ cancer patient from the beginning of the COVID-19 pandemic whose virus quasispecies across multiple timepoints carried several immune escape mutations found in more contemporary VOC, such as alpha, delta and omicron, that appeared to be selected for during infection. We hypothesize that immunosuppressed patients may represent the source of VOC seen throughout the COVID-19 pandemics.

7.
J Formos Med Assoc ; 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1977473

ABSTRACT

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is common in critically ill patients with COVID-19 and is associated with worse outcomes. However, reports on CAPA and its impact on treatment outcomes in Asian populations are limited. METHODS: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction-confirmed COVID-19 admitted to intensive care units (ICUs) were retrospectively enrolled in this observational study. The incidence rate of CAPA during ICU admission was investigated. The clinical factors associated with CAPA, including corticosteroid exposure, were analyzed. The impact of CAPA on the treatment outcomes and SARS-CoV-2 viral shedding were explored. RESULTS: A total of 72 ICU-admitted patients with COVID-19 were included in the analysis. The incidence rate of CAPA was 15.3% (11/72) in all patients and 23% (11/48) in the mechanically ventilated patients. The median time from ICU admission to CAPA diagnosis was 15 days. A lower fibrinogen level (adjusted odds ratio [aOR], 0.983; 95% confidence interval [CI], 0.967-0.999) was independently associated with CAPA. The patients with CAPA had a higher in-hospital mortality rate (55% vs. 13%, p = 0.001) and a longer SARS-CoV-2 viral shedding time (22 days vs. 16 days, p = 0.037) than those without CAPA. CONCLUSION: Lower serum fibrinogen levels was independently associated with CAPA among the ICU-admitted patients with COVID-19. The patients with CAPA had a higher in-hospital mortality rate and a longer SARS-CoV-2 viral shedding time than those without CAPA.

8.
International Journal of Clinical and Experimental Medicine ; 15(7):231-235, 2022.
Article in English | EMBASE | ID: covidwho-1976313

ABSTRACT

Background: COVID-19 is caused by infection with a new form of coronavirus (SARS-CoV-2). The WHO raised the COVID-19 alert to the highest level. The virus is a highly contagious via human-to-human transmission. The median duration of viral shedding is 20.0 days. We report a long duration of viral shedding that was 32.0 days from illness onset in a patient with moderate COVID-19 admitted to Qianjiang Central Hospital. Case report: A 37-year-old patient sought medical advice while suffering from fever, dry cough, fatigue, dizziness, runny nose and diarrhoea. Five days before the visit, he had a history of travel from affected geographic areas. The patient had a positive RT-PCR test, and chest CT images showed multiple nodules and mixed ground-glass opacification with consolidation in bilaterally in the lungs. Laboratory findings showed that the lymphocyte and CD4+ counts were below the normal range. The patient was given antiviral treatment, including arbidol, lopinavir, IFN-α, and traditional Chinese medicine, and other necessary supportive care. All clinical symptoms and CT imaging manifestation ab-normalities resolved during the course of therapy. Conclusion: Although the positive RT-PCR tests were verified in consecutive upper respiratory specimens, the patient’s clinical symptoms, CT imaging findings, CD4+ lymphocyte counts, and IgG antibody levels had obviously improved. Positive tests may be detecting pieces of inactive viruses, which would not be transmissible in individual cases.

9.
Nephrology (Carlton) ; 27(10): 804-809, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1968171

ABSTRACT

AIM: It is unclear if variant of concern and vaccination status impact COVID-19 infection virological dynamics in haemodialysis patients and affect de-isolation protocol for dialysis centres. METHOD: We performed a retrospective observational cohort study between February 2020 to September 2021, to examine the virological kinetics of vaccinated and unvaccinated haemodialysis patients with polymerase chain reaction (PCR)-confirmed COVID-19 infection of the delta and pre-delta variants. RESULTS: Of the 38 subjects with PCR-confirmed COVID-19 infection, we found that individuals infected during the delta-variant period had higher viral load at presentation and required longer duration to achieve a negative PCR swab, compared to those infected in the pre-delta variant period. Time to achieve negative PCR swab was longest in unvaccinated individuals infected during delta-variant period. However, vaccinated and unvaccinated individuals achieved high PCR cycle threshold value of ≥25 and ≥30 at similar timing. CONCLUSION: Our study suggests that patients infected during delta-variant period of COVID-19 illness, have higher viral load at presentation and prolonged viral shedding, especially in the unvaccinated cohort. However, prolonged time to negative PCR is likely due to inactive virus shedding, and that conversion to negative PCR may not be a necessary pre-requisite for de-isolation.


Subject(s)
COVID-19 , Kidney Failure, Chronic , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Retrospective Studies , SARS-CoV-2 , Vaccination
10.
Journal of Swine Health and Production ; 30(3):145-148, 2022.
Article in English | EMBASE | ID: covidwho-1970073

ABSTRACT

Using retrospective data from 6 breedto- wean herds over 4 years, porcine reproductive and respiratory syndrome virus (PRRSV) statuses were assigned by week according to the 2021 American Association of Swine Veterinarians PRRSV classification. Productivity changes were characterized as herds transitioned through status categories. Overall, productivity improved as farm status improved.

11.
Frontiers in Pharmacology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1969055

ABSTRACT

Background: Qingfei Paidu decoction (QFPDD) has been widely used in treating coronavirus disease 2019 (COVID-19) in China. However, studies on the treatment effect of COVID-19 patients and other respiratory diseases have not been well demonstrated. Our study aims to determine the treatment effect of QFPDD in combination with conventional treatment on COVID-19 patients and other respiratory diseases. Methods: This retrospective study recruited COVID-19 patients who were treated with QFPDD for at least two courses (6 days) from seven hospitals in five provinces from January 21 to March 18 2020. Demographic, epidemiological, clinical, laboratory, computed tomography characteristics, treatment, and outcome data were collected and analyzed. The improvements in clinical symptoms before and after QFPDD treatment were compared. Results: Eight COVID-19 patients were included in this study. Of them, six were males (75.0%). The median age of the patients was 66 (60–82) years. Four patients were classified as mild and moderate cases (50.0%);there were two severe cases (25.0%) and critical cases (25.0%). The most common symptom was cough (7 [87.5%]), followed by fever (6 [75.0%]), fatigue (4 [50.0%]), asthma (4 [50.0%]), and anorexia (3 [37.5%]). Abnormal findings included decrease in neutrophils (3 [37.5%]), lymphocytes (2 [25.0%]), alkaline phosphatase (3 [37.5%]), lactic dehydrogenase (4 [50.0%]), erythrocyte sedimentation rate (2 [25.0%]), and C-reactive protein (5 [83.3%]) at admission. After one course (3 days) of QFPDD, nasal obstruction and sore throat completely disappeared, and fever (5 [83.3%]), fatigue (2 [50.0%]), and cough (2 [28.6%]) were improved. After two courses (6 days), the fever disappeared completely in all patients, and the other symptoms showed a tendency to improve. In non-severe patients, 87.5% baseline symptoms completely disappeared. In severe patients, 61.1% of the baseline symptoms completely disappeared after patients were administered QFPDD for two courses. Of the abnormal indicators, 55.6% returned to normal levels. The median duration to complete fever recovery was 1.0 day. The median durations of viral shedding and hospitalization were 10.5 and 21.5 days, respectively. None of the patients worsened and died, and no serious adverse events occurred related to QFPDD during hospitalization. Conclusion: QFPDD combined with conventional treatment improved clinical symptoms in COVID-19 patients with other respiratory diseases, and no serious adverse reactions associated with QFPDD were observed. Larger sample studies confirm our findings in the future.

12.
Gastroenterology ; 162(7):S-285, 2022.
Article in English | EMBASE | ID: covidwho-1967273

ABSTRACT

SARS-CoV-2 shedding in feces has been reported. We aimed to find: (1)The predictors of fecal viral shedding, (2)Incidence of post-infectious FGIDs in patients with COVID-19 infection. Methods: 188 COVID-19 patients admitted from March to July 2020 were included and prospectively collected the stool samples on admission date and then weekly until negative results. We recorded the clinical and laboratory profiles to find the predictors of fecal viral shedding. Baseline GI symptoms before COVID-19 infection were also evaluated. After discharged, patients were followed regarding their GI symptoms by telephone interviews at 3 and 9 months to evaluate the incidence of post COVID-19 irritable bowel syndrome (IBS), functional constipation (FC), and functional dyspepsia (FD) by using Rome IV criteria. Results: 127 of 188 patients completed stool collection protocol, 85 patients (66.9%) had positive stool SARS-CoV-2 with a duration of viral shedding of 79 (76-90) days. Disease severity, presence of pneumonia, fever, respiratory symptoms, vomiting, and diarrhea were not significantly different between patients with and without fecal viral shedding. Patients with stool shedding had higher prevalence of anosmia [5(83.3%) vs 0, p=0.048], lower absolute lymphocyte [1.42(0.96-1.77) x109/L vs 1.84(1.27-2.17) x109/L, p=0.004], higher ALT [27(18.25-36.75) U/L vs 19(13-28.5) U/L, p=0.02] and lower cycle threshold values [19.68 (16.35-26.40) vs 26.28 (19.34-33.31), p=0.05] (table1). Multivariate analysis including age, diabetes, diarrhea, hemoglobin, absolute lymphocyte, platelet count, ALT, and cycle threshold values demonstrated that there was no factor associated with viral shedding in the stool. 84 patients (44.7%) responsed to the follow-up phone call at 9 months. 3 patients (3.6%) had new onset of GI symptoms during 9-month post COVID-19 infection [early satiety (n=1), diarrhea (n=1), constipation (n=2) and abdominal pain (n=2) with mean severity (SD):8.5 (0.5)of 10]. One patient (1.2%) had FD, No IBS was diagnosed. Conclusions: More than a half of COVID-19 patients had viral shedding in stool for up to 3 months. Univariate analysis demonstrated that low blood lymphocyte and lower cycle threshold values were associated with fecal viral shedding but not the GI symptoms during admission. However, multivariate analysis demonstrated that these factors were not associated with fecal viral shedding. Post-infectious functional GI disorders were uncommon. (Table Presented)

13.
Journal of Research in Medical Sciences ; 27(1):43, 2022.
Article in English | EMBASE | ID: covidwho-1957520

ABSTRACT

Background: Since December 2019, the world is struggling with an outbreak of coronavirus disease-2019 (COVID-19) infection mostly represented as an acute respiratory distress syndrome and has turned into the most critical health issue worldwide. Limited information is available about the association between dynamic changes in the naso/oropharyngeal viral shedding in infected patients and biomarkers, aiming to be assessed in the current study. Materials and Methods: This quasi-cohort study was conducted on 31 patients with moderate severity of COVID-19 manifestations, whose real-time polymerase chain reaction (RT-PCR) test was positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA at baseline. RT-PCR was rechecked for patients every 3-4 days until achieving two negative ones. In parallel, biomarkers, including lymphocyte count, lactate dehydrogenase (LDH), and C-reactive protein (CRP), were assessed every other day, as well. Viral shedding also was assessed. Results: Spearman's correlation test revealed a significant direct correlation between the viral shedding from the symptom onset and the time, in which CRP (P = 0.0015, r = 0.54) and LDH (P = 0.001, r = 0.6207) return to normal levels after symptom onset, but not for lymphocyte count (P = 0.068, r = 0.34). Conclusion: Based on the current study's findings, the duration of SARS-CoV-2 RNA shedding was directly correlated with the required time for LDH and CRP return to normal levels. Therefore, these factors can be considered the determinants for patients' discharge, isolation, and return to social activities;however, further investigations are required to generalize the outcomes.

14.
Indian Journal of Public Health Research and Development ; 13(3):19-23, 2022.
Article in English | EMBASE | ID: covidwho-1939752

ABSTRACT

COVID 19 PANDEMIC has stricken in multiple waves, crippling the nation with each strike. Attempts at curbing its spread has been focused on a few established modes of transmission. Current literature evidence suggests possibility of Feco-oral transmission, detection of viable virus in stools of covid infected individuals, viral shedding several weeks post recovery and potential persistence of viable virus in sewage. Guidelines and protocols laid down have not included this potentially dangerous mode of spread. Many countries including Australia, Finland etc have utilized waste water epidemiology as a tool in surveillance. This can be used as a warning signal for early detection and control. This review article proposes the addition of new guidelines in this spectre to aid in curbing the spread of pandemic as well as adopting sewage surveillance as a tool in primary prevention.

15.
Clin Infect Dis ; 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1927310

ABSTRACT

BACKGROUND: Patterns of shedding replication-competent SARS-CoV-2 in severe or critical COVID-19 are not well-characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical COVID-19. METHODS: We enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19. Respiratory specimens were collected at predefined intervals and tested for SARS-CoV-2 using virus culture and RT-qPCR. Clinical and epidemiologic metadata were reviewed. RESULTS: We collected 529 respiratory specimens from 78 patients. Replication-competent virus was detected in 4 of 11 (36.3%) immunocompromised patients up to 45 days after symptom onset, and in 1 of 67 (14.9%) immunocompetent patients 10 days after symptom onset (P = 0.001). All culture-positive patients were in the ICU cohort and had persistent or recurrent symptoms of COVID-19. Median time from symptom onset to first specimen collection was 15 days (range, 6-45) for ICU patients and 58.5 days (range, 34-139) for LTACH patients. SARS-CoV-2 RNA was detected in 40 of 50 (80%) ICU patients and 7 of 28 (25%) LTACH patients. CONCLUSIONS: Immunocompromise and persistent or recurrent symptoms were associated with shedding of replication-competent SARS-CoV-2, supporting the need for improving respiratory symptoms in addition to time as criteria for discontinuation of transmission-based precautions. Our results suggest that the period of potential infectiousness among immunocompetent patients with severe or critical COVID-19 may be similar to that reported for patients with milder disease.

16.
Nephrology Dialysis Transplantation ; 37(SUPPL 3):i490, 2022.
Article in English | EMBASE | ID: covidwho-1915733

ABSTRACT

BACKGROUND AND AIMS: A great amount of information has been divulged on the epidemiology and outcome of coronavirus disease 2019 (COVID-19) in patients with ESRD. The majority of the studies have been conducted in patients on maintenance hemodialysis (HD) and kidney transplant recipients. Unfortunately, few studies focused on the outcome of peritoneal dialysis (PD) patients. Information regarding this subset of the population has been extrapolated from aggregated data including a higher percentage of HD patients. As a result, the impact of COVID-19 is indefinite in patients receiving PD. We conducted a study to better understand how patients on PD have been affected by COVID-19. METHOD: We conducted a single-center retrospective analysis of 141 PD patients followed at the University Hospital of Modena, Italy from 1 March 2020 to 31 December 2021. The diagnosis of COVID-19 was performed through nasopharyngeal swab RT-PCR testing. Duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding measured the time elapsed from diagnosis of COVID-19 to one or two (if available) negative nasopharyngeal PCR tests. Median and interquartile range or mean and standard deviation were used for continuous variables and percentage for categorical variables. A P-value <0.05 was considered statistically significant. RESULTS: During the pandemic, 18 out of 141 (12.7%) patients receiving PD dialysis contracted COVID-19. Median age was 60 (50.2-66.5) years with a predominance of males (72.2%) The percentage of patients on APD accounted for 33.3%. The infection was symptomatic in out of 18 (94.4%) patients. Fever (94.4%) and cough (55.6%) were the most common symptoms. Viral shedding, traced with nasopharyngeal swabs lasted 26 (14.5-3.5) days. Two patients were inactive on the waiting list for kidney transplantation for a mean of 43 ± 1.4 days. COVID-19 caused hospital admission of seven (38.9%) patients. During hospitalization two (11.1%) patients switched from PD to HD for ultrafiltration failure and inadequate solute clearance and two (11.1%) died for septic shock with multiorgan failure. In our cohort of patients, excess death due to COVID-19 was 22.2%. Half of the patients contracted the infection before the availability of SARS-CoV-2 vaccine. There were no statistically significant differences between vaccinated and unvaccinated patients in terms of symptoms, viral shedding and hospital admission or (Table 1). We underline that COVID-19 was fatal only in two unvaccinated patients. CONCLUSION: This study reports the monocentric experience of a large PD center during the COVID-19 pandemic. COVID-19 was symptomatic in the majority of patients and led to hospitalization of about 40% of the patients. The rate of symptoms, viral shedding and hospital admission was similar between vaccinated and unvaccinated patients. Two unvaccinated patients died for the severe consequence of COVID-19.

17.
Topics in Antiviral Medicine ; 30(1 SUPPL):66-67, 2022.
Article in English | EMBASE | ID: covidwho-1880427

ABSTRACT

Background: Transmission of SARS-CoV-2 is highly heterogeneous, with a small fraction of infected individuals (often referred to as "superspreaders") contributing a disproportionate share of forward transmission. Numerous behavioral and environmental explanations have been offered to explain transmission heterogeneity, but the extent to which the underlying features of the infection process within individual hosts contribute towards the superspreading phenomenon remains unclear. In addition, it is not clear how vaccination would impact on the viral infection dynamics and thus the infectiousness of individuals. Addressing these gaps in knowledge will inform the design of more targeted and effective strategies for controlling community spread. Methods: In a study on UIUC campus (UIUC SHIELD), the dynamics of infectious virus and viral RNA shedding were captured through daily longitudinal sampling of 72 individuals for up to 14 days (60 unvaccinated and 12 vaccinated). We fitted mechanistic models to both viral loads and cell culture positivity data, and directly estimated viral reproduction and clearance rates, and overall infectiousness for each individual. Results: Integrating mathematical models with viral load and cell culture positivity data, we show a substantial level of heterogeneity in infectiousness of individual. In unvaccinated individuals, peak viral loads and clearance kinetics of B.1.1.7 and non-variant of concern viruses were indistinguishable. In vaccinated individuals, the viral dynamics do not follow typical patterns of acute infection dynamics and we estimate that these individuals are much less infectious than unvaccinated individuals. Conclusion: Our work provides a high-resolution portrait of SARS-CoV-2 infection dynamics. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Vaccinated individuals are less infectious than unvaccinated individuals overall.

18.
Topics in Antiviral Medicine ; 30(1 SUPPL):37-38, 2022.
Article in English | EMBASE | ID: covidwho-1880239

ABSTRACT

Background: Post-Acute Sequelae of SARS-CoV-2 (PASC) is characterized by persistent symptoms negatively impacting quality of life several weeks after SARS-CoV-2 diagnosis. Proposed risk factors include older age, female sex, comorbidities, and severe COVID-19, including hospitalization and oxygen requirement. Yet, associations of these factors with prolonged symptoms remain poorly understood globally. Methods: The global, observational cohort study HVTN 405/HPTN 1901 characterizes the clinical and immunologic course in the first year after SARS-CoV-2 infection among adults. The cohort was categorized by infection severity (asymptomatic;symptomatic with no oxygen requirement [NOR];non-invasive oxygen requirement [NIOR];or invasive oxygen requirement [IOR]). A regression model was applied to estimate geometric mean ratios (GMR) for duration and odds ratios (OR) for persistence of symptoms. Results: 759 participants from Peru (25.2%), USA (26.0%), Republic of South Africa (RSA, 37.7%), and non-RSA Sub-Saharan Africa (11.2%) were enrolled a median of 51 (IQR 35-66) days post-diagnosis, from May 2020 to Mar 2021. 53.8% were female, 69.8% were <55yo (median 44yo, IQR 33-58) and identified as non-Hispanic Black (42.7%), Hispanic (27.9%) or non-Hispanic White (15.8%). Comorbidities included obesity (42.8%), hypertension (24%), diabetes (14%), HIV infection (11.6%) and lung disease (7.5%). 76.2% were symptomatic (NOR 47.4%;NIOR 22.9%;and IOR 5.8%). Among symptomatic participants, median acute COVID-19 duration was 20 days (IQR 11-35);43.3% had ≥1 persistent symptom after COVID-19 resolution (39.8% NOR;49.1 % NIOR+IOR;p=0.037);16.8% reported ≥1 symptom >42 days (14.0% NOR;21.6% NIOR+IOR;p=0.025). Symptom duration was not associated with age or sex assigned at birth but was associated with disease severity (GMR 2.09;95%CI 1.5-2.91, p<0.001 for NIOR vs NOR;not significant for IOR vs NIOR), lung disease (GMR 2.43;95%CI 1.42-4.16, p=0.001), and global region (p<0.05, see Figure 1). Prolonged viral shedding was associated with persistent diarrhea (OR 6.59;95%CI 1.65-26.86;p=0.008). Conclusion: A recovery course consistent with PASC was significantly associated with infection severity, lung disease, and region. Regional differences in symptom profiles and duration may be influenced by viral diversity, genetic, or cultural factors and likely reflect disparities in healthcare access and interventions. Better understanding PASC associations may improve clinical assessment and management globally.

19.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338241

ABSTRACT

We aimed at investigating host-virus co-metabolism during SARS-CoV-2 infection. Therefore, we extended comprehensive sex-specific, whole-body organ resolved models of human metabolism with the necessary reactions to replicate SARS-CoV-2 in the lung as well as selected peripheral organs. Using this comprehensive host-virus model, we obtained the following key results: 1. The predicted maximal possible virus shedding rate was limited by isoleucine availability. 2. The supported initial viral load depended on the increase in CD4+ T-cells, consistent with the literature. 3. During viral infection, the whole-body metabolism changed including the blood metabolome, which agreed well with metabolomic studies from COVID-19 patients and healthy controls. 4. The virus shedding rate could be reduced by either inhibition of the guanylate kinase 1 or availability of amino acids, e.g., in the diet. 5. The virus variants achieved differed in their maximal possible virus shedding rates, which could be inversely linked to isoleucine occurrences in the sequences. Taken together, this study presents the metabolic crosstalk between host and virus and emphasis the role of amino acid metabolism during SARS-CoV-2 infection, in particular of isoleucine. As such, it provides an example of how computational modelling can complement more canonical approaches to gain insight into host-virus crosstalk and to identify potential therapeutic strategies.

20.
Journal of Bio-X Research ; 5(1):27-34, 2022.
Article in English | EMBASE | ID: covidwho-1816311

ABSTRACT

Objective: The coronavirus disease 2019 (COVID-19) epidemic resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has still spread globally. The occurrence of the Delta variant, which is more infectious and spreads faster than earlier forms of the virus that causes COVID-19, makes infection prevention more challenging. Therefore, this study aimed to gain a comprehensive insight into the transmission routes of SARS-CoV-2 for curbing the propagation of SARS-CoV-2 in human populations. Methods: We studied a prospective cohort of 576 patients admitted consecutively to the First Affiliated Hospital of Guangzhou Medical University from January 21 to June 8, 2020. These patients were chosen based on their similar clinical phenotypes or imaging findings. There were 21 (3.6%) laboratory-confirmed COVID-19 patients (16 severe and 5 mild cases) and 555 non-COVID-19 patients. The antibody response and routes and duration of viral shedding were systematically evaluated in serial clinical specimens. Moreover, SARS-CoV-2 RNA was also detected in a mouth rinse, urine, and tear samples. This study was approved by the Medical Ethical Committee of The First Affiliated Hospital of Guangzhou Medical University (approval No. 2020-77). Results: SARS-CoV-2 mainly existed in sputum, nasal and throat swabs, and feces samples. Virus latency was longer in sputum and feces samples than in nasopharyngeal samples. IgG antibody response in respiratory samples was related to disease severity. Although droplets and aerosols are the major transmission routes for COVID-19, covert routes of transmission from asymptomatic patients, contaminated surfaces, and wastewater are also of interest. Conclusion: Our findings provide a solid foundation for developing prophylactic measures against SARS-CoV-2.

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