Iatrogenic immunosuppression can lead to prolonged viral shedding and absent immune response to COVID-19.
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ABSTRACT:
SUBMITTER: Psaros Einberg A
PROVIDER: S-EPMC8222928 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecently, more patients who recovered from the novel coronavirus disease 2019 (COVID-19) may later test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) again using reverse transcription-polymerase chain reaction (RT-PCR) testing. Even though it is still controversial about the possible explanation for clinical cases of long-term viral shedding, it remains unclear whether the persistent viral shedding means re-infection or recurrence.MethodsSpecimens were collected from three COVID-19-confirmed patients, and whole-genome sequencing was performed on these clinical specimens during their first hospital admission with a high viral load of SARS-CoV-2. Laboratory tests were examined and analyzed throughout the whole course of the disease. Phylogenetic analysis was carried out for SARS-CoV-2 haplotypes.ResultsWe found haplotypes of SARS-CoV-2 co-infection in two COVID-19 patients (YW01 and YW03) with a long period of hospitalization. However, only one haplotype was observed in the other patient with chronic lymphocytic leukemia (YW02), which was verified as one kind of viral haplotype. Patients YW01 and YW02 were admitted to the hospital after being infected with COVID-19 as members of a family cluster, but they had different haplotype characteristics in the early stage of infection; YW01 and YW03 were from different infection sources; however, similar haplotypes were found together.ConclusionThese findings show that haplotype diversity of SARS-CoV-2 may result in viral adaptation for persistent shedding in multiple recurrences of COVID-19 patients, who met the discharge requirement. However, the correlation between haplotype diversity of SARS-CoV-2 virus and immune status is not absolute. It showed important implications for the clinical management strategies for COVID-19 patients with long-term hospitalization or cases of recurrence.
| S-EPMC8631178 | biostudies-literature
Project description:COVID-19 has surfaced as a multi-organ disease predominantly affecting the respiratory system. Detection of the viral RNA through reverse transcriptase-PCR (RT-PCR) from a nasopharyngeal or throat sample is the preferred method of diagnosis. Recent evidence has suggested that COVID-19 patients can shed the SARS-CoV-2 for several weeks. Herein, we report six cases of COVID-19 who had persistently positive SARS-CoV-2 on repeat RT-PCR testing reaching up to 9 weeks. The spectrum of cases described ranges from asymptomatic infection to severe COVID-19 pneumonia. A full understanding of the virus's transmission dynamics needs further research. Prolonged viral shedding currently has unclear implications on the management and isolation decisions-the role of the cycle threshold (Ct) value in guiding therapeutic decisions is yet to be clarified. More data on the relationship between Ct values and viral cultivation are needed, especially in patients with prolonged viral shedding, to understand the virus's viability and infectivity.
| S-EPMC8045623 | biostudies-literature
Project description:Since December 2019, Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic. We aimed to investigate the clinical characteristics and analyzed the risk factors for prolonged viral RNA shedding. We retrospectively collected data from 112 hospitalized COVID-19 patients in a single center in Wuhan, China. Factors associated with prolonged viral RNA shedding (?28 days) were investigated. Forty-nine (43.8%) patients had prolonged viral RNA shedding. Patients with prolonged viral shedding were older and had a higher rate of hypertension. Proinflammatory cytokines, including interleukin-2R (IL-2R) and tumor necrosis factor-? (TNF-?), were significantly elevated in patients with prolonged viral shedding. Multivariate analysis revealed that hypertension, older age, lymphopenia and elevated serum IL-2R were independent risk factors for prolonged viral shedding. This comprehensive investigation revealed the distinct characteristics between patients with or without prolonged viral RNA shedding. Hypertension, older age, lymphopenia and high levels of proinflammatory cytokines may be correlated with prolonged viral shedding.
| S-EPMC7554496 | biostudies-literature
Project description:The studies of coronavirus disease 2019 (COVID-19) have mainly focused on epidemiological and clinical features of patients, but transmission dynamics of SARS-CoV-2 virus after patients have recovered is still poorly understood. Here we report a case with prolonged viral shedding of COVID-19 in Kaohsiung, Taiwan. This patient started to show myalgia and malaise in Wuhan, and the onset of the fever was on days 7-14 of the illness. All clinical and radiological results returned to normal after day 26, however, viral shedding was still evident 14 days later. Sequence analysis of the genome of the Taiwanese SARS-CoV-2 isolate from this patient reveals new mutations in viral replicase and ORF3a, indicating that COVID-19 evolves very quickly. Prolonged viral shedding and new mutations in the viral genome could potentially complicate the control of the COVID-19 pandemic.
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Project description:Coronavirus disease 2019 (COVID-19) is a global pandemic associated with a high mortality. Our study aimed to determine the clinical risk factors associated with disease progression and prolonged viral shedding in patients with COVID-19. Consecutive 564 hospitalized patients with confirmed COVID-19 between January 17, 2020 and February 28, 2020 were included in this multicenter, retrospective study. The effects of clinical factors on disease progression and prolonged viral shedding were analyzed using logistic regression and Cox regression analyses. 69 patients (12.2%) developed severe or critical pneumonia, with a higher incidence in the elderly and in individuals with underlying comorbidities, fever, dyspnea, and laboratory and imaging abnormalities at admission. Multivariate logistic regression analysis indicated that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), hypertension without receiving angiotensinogen converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) therapy (OR, 2.29; 95% CI, 1.14-4.59), and chronic obstructive pulmonary disease (OR, 7.55; 95% CI, 2.44-23.39) were independent risk factors for progression to severe or critical pneumonia. Hypertensive patients without receiving ACEI/ARB therapy showed higher lactate dehydrogenase levels and computed tomography (CT) lung scores at about 3 days after admission than those on ACEI/ARB therapy. Multivariate Cox regression analysis revealed that male gender (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46), receiving lopinavir/ritonavir treatment within 7 days from illness onset (HR, 0.75; 95% CI, 0.63-0.90), and receiving systemic glucocorticoid therapy (HR, 1.79; 95% CI, 1.46-2.21) were independent factors associated with prolonged viral shedding. Our findings presented several potential clinical factors associated with developing severe or critical pneumonia and prolonged viral shedding, which may provide a rationale for clinicians in medical resource allocation and early intervention.
| S-EPMC7505267 | biostudies-literature
Project description:Despite the introduction of vaccines, COVID-19 still affects millions of people worldwide. A better understanding of pathophysiology and the discovery of novel therapies are needed. One of the cells of interest in COVID-19 is the neutrophil. This cell type is being recruited to a site of inflammation as one of the first immune cells. In this project, we investigated a variety of neutrophils phenotypes during COVID-19 by measuring the expression of markers for migration, maturity, activation, gelatinase granules and secondary granules using flow cytometry. We show that neutrophils during COVID-19 exhibit altered phenotypes compared to healthy individuals. The activation level including NETs production and maturity of neutrophils seem to last longer during COVID-19 than expected for innate immunity. Neutrophils as one of the drivers of severe cases of COVID-19 are considered as potential treatment targets. However, for a successful implementation of treatment, there is a need for a better understanding of neutrophil functions and phenotypes in COVID-19. Our study answers some of those questions.
| S-EPMC9200737 | biostudies-literature
Project description: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.
| S-EPMC8711078 | biostudies-literature
Project description: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.
| S-EPMC8523010 | biostudies-literature
Project description:A key parameter in epidemiological modeling which characterizes the spread of an infectious disease is the generation time, or more generally the distribution of infectiousness as a function of time since infection. There is increasing evidence supporting a prolonged viral shedding window for COVID-19, but the transmissibility in this phase is unclear. Based on this, we develop a generalized Susceptible-Exposed-Infected-Resistant (SEIR) model including an additional compartment of chronically infected individuals who can stay infectious for a longer duration than the reported generation time, but with infectivity reduced to varying degrees. Using the incidence and fatality data from different countries, we first show that such an assumption also yields a plausible model in explaining the data observed prior to the easing of the lockdown measures (relaxation). We then test the predictive power of this model for different durations and levels of prolonged infectiousness using the incidence data after the introduction of relaxation in Switzerland, and compare it with a model without the chronically infected population to represent the models conventionally used. We show that in case of a gradual easing on the lockdown measures, the predictions of the model including the chronically infected population vary considerably from those obtained under a model in which prolonged infectiousness is not taken into account. Although the existence of a chronically infected population still remains largely hypothetical, we believe that our results provide tentative evidence to consider a chronically infected population as an alternative modeling approach to better interpret the transmission dynamics of COVID-19.
| S-EPMC7875355 | biostudies-literature
Project description:Background/purposeCoronavirus 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.MethodsPatients 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.ResultsA 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.ConclusionLower 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.
| S-EPMC9359693 | biostudies-literature