scholarly journals Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric C. Rouchka ◽  
Julia H. Chariker ◽  
Brian Alejandro ◽  
Robert S. Adcock ◽  
Richa Singhal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Critical Factor ◽  
Interferon Response ◽  
Upper Respiratory Tract ◽  
Viral Loads ◽  
Antiviral Responses ◽  
Upper Respiratory

AbstractKey elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.

scholarly journals Association between upper respiratory tract viral load, comorbidities, disease severity and outcome of patients with SARS-CoV-2 infection

2021 ◽  
Author(s):  
Helena C Maltezou ◽  
Vasilios Raftopoulos ◽  
Rengina Vorou ◽  
Kalliopi Papadima ◽  
Kassiani Mellou ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Disease Severity ◽  
High Viral Load ◽  
P Value ◽  
Upper Respiratory Tract ◽  
Limited Information ◽  
Symptomatic Disease ◽  
Viral Loads ◽  
Upper Respiratory

Abstract Background There is limited information on the association between upper respiratory tract (URT) viral loads, host factors, and disease severity in SARS-CoV-2 infected patients. Methods We studied 1,122 patients (mean age: 46 years) diagnosed by PCR. URT viral load, measured by PCR cycle threshold, was categorized as high, moderate or low. Results There were 336 (29.9%) patients with comorbidities; 309 patients (27.5%) had high, 316 (28.2%) moderate, and 497 (44.3%) low viral load. In univariate analyses, compared to patients with moderate or low viral load, patients with high viral load were older, had more often comorbidities, developed symptomatic disease, were intubated and died; in addition, patients with high viral load had longer stay in intensive care unit and longer intubation compared to patients with low viral load (p-values <0.05 for all). Patients with chronic cardiovascular disease, hypertension, chronic pulmonary disease, immunosuppression, obesity and chronic neurological disease had more often high viral load (p-value<0.05 for all). Multivariate analysis found that a high viral load was associated with COVID-19. The level of viral load was not associated with any other outcome. Conclusions URT viral load could be used to identify patients at higher risk for morbidity or severe outcome.

scholarly journals Viral load in upper respiratory tract of COVID-19 patients detected by digital PCR

2020 ◽  
Author(s):  
Jiankang Zhao ◽  
Haibo Li ◽  
Hui Li ◽  
Qiaoling Wu ◽  
Ke Wu ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Digital Pcr ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Lung Lesions ◽  
Viral Loads ◽  
Ct Value ◽  
Upper Respiratory ◽  
Close Contacts

Abstract Background: Upper respiratory tract specimens are widely applicable for the diagnosis of COVID-19. To date, no study has analyzed the actual viral loads in upper respiratory tract and its relationship with the severity of lung lesions, Ct value of RT-PCR and transmission capacity in COVID-19 patients.Methods: We retrospectively enrolled nine COVID-19 patients. Clinical data and close contacts of these patients were investigated. Respiratory samples were tested for SARS-CoV-2 with both normal RT-PCR and droplet digital PCR.Results: All the COVID-19 patients complicated with pneumonia. Viral loads in nasopharyngeal swabs were accurately quantified, and they had no direct correspondence with the severity of lung lesions. The Cycle Threshold (Ct) value of RT-PCR was approximately consistent with the absolute quantification of digital PCR. The spearman correlation coefficient between them was -0.952 with P value < 0.001. Close contacts of patients with very low viral load or no detected virus were not infected.Conclusions: Viral loads in nasopharyngeal swabs, could not predict the severity of lung lesions revealed by CT in COVID-19 patients. The infectious capacity of patients with low or absent viral load in upper respiratory tract was relatively weak, and wearing mask might be helpful for lower its spread.

scholarly journals Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association with Viral Load, Independent of Symptoms

2021 ◽  
Author(s):  
Diem-Lan Vu ◽  
Paola Martinez-Murillo ◽  
Fiona Pigny ◽  
Maria Vono ◽  
Benjamin Meyer ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Upper Respiratory Tract ◽  
University Hospitals ◽  
Viral Loads ◽  
Gm Csf ◽  
Cytokine Levels ◽  
Control Virus ◽  
Upper Respiratory ◽  
Local Recruitment

Abstract Background SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches. Methods SARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal wash and serum specimens from a subset of patients were collected to measure viral load, IgA specific for the S1 domain of the spike protein, and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms. Results Samples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia. Some patients had S1-specific IgA in the nasal cavity while almost none had IgG. Conclusion The nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this mild COVID-19 cohort, anosmia was not associated with increases in any locally produced cytokines.

scholarly journals Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association With Viral Load, Independent of Symptoms

2021 ◽  
Author(s):  
Arnaud Didierlaurent ◽  
Vu Diem-Lan ◽  
Paola Martinez Murillo ◽  
Fiona Pigny ◽  
Maria Vono ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Upper Respiratory Tract ◽  
University Hospitals ◽  
Viral Loads ◽  
Gm Csf ◽  
Cytokine Levels ◽  
Control Virus ◽  
Upper Respiratory ◽  
Local Recruitment

Abstract BackgroundSARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches.MethodsSARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal-wash and serum specimens from a subset of patients were collected to measure viral load and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms.ResultsSamples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia.ConclusionsThe nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this cohort, anosmia was not associated with increases in any locally produced cytokines.

scholarly journals Kinetics of SARS-CoV-2 infection in the human upper and lower respiratory tracts and their relationship with infectiousness

2020 ◽  
Author(s):  
Ruian Ke ◽  
Carolin Zitzmann ◽  
Ruy M. Ribeiro ◽  
Alan S. Perelson
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Dynamic Models ◽  
Target Cells ◽  
Upper Respiratory Tract ◽  
Viral Kinetics ◽  
Viral Loads ◽  
Viral Load Data ◽  
Upper Respiratory ◽  
Kinetics Of

SARS-CoV-2 is a human pathogen that causes infection in both the upper respiratory tract (URT) and the lower respiratory tract (LRT). The viral kinetics of SARS-CoV-2 infection and how they relate to infectiousness and disease progression are not well understood. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection in both the URT and LRT. We fit the models to viral load data from patients with likely infection dates known, we estimated that infected individuals with a longer incubation period had lower rates of viral growth, took longer to reach peak viremia in the URT, and had higher chances of presymptomatic transmission. We then developed a model linking viral load to infectiousness. We found that to explain the substantial fraction of transmissions occurring presymptomatically, the infectiousness of a person should depend on a saturating function of the viral load, making the logarithm of the URT viral load a better surrogate of infectiousness than the viral load itself. Comparing the roles of target-cell limitation, the innate immune response, proliferation of target cells and spatial infection in the LRT, we found that spatial dissemination in the lungs is likely to be an important process in sustaining the prolonged high viral loads. Overall, our models provide a quantitative framework for predicting how SARS-CoV-2 within-host dynamics determine infectiousness and represent a step towards quantifying how viral load dynamics and the immune responses determine disease severity.

scholarly journals Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magen E. Francis ◽  
Brian Richardson ◽  
Una Goncin ◽  
Mara McNeil ◽  
Melissa Rioux ◽  
...  
Keyword(s):  
Interferon Response ◽  
Upper Respiratory Tract ◽  
Age Bias ◽  
Antiviral Responses ◽  
Male Sex ◽  
Upper Respiratory ◽  
Interferon Responses ◽  
The Impact ◽  
Insight Into ◽  
Older Males

AbstractSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

scholarly journals Asymptomatic COVID-19 Adult Outpatients identified as Significant Viable SARS-CoV-2 Shedders 

2021 ◽  
Author(s):  
Marie Glenet ◽  
Anne-Laure Lebreil ◽  
Laetitia Heng ◽  
Yohan N’Guyen ◽  
Ittah Meyer ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Control Measures ◽  
Upper Respiratory Tract ◽  
Rna Detection ◽  
Viral Loads ◽  
Infection Control Measures ◽  
Infected Adult ◽  
Asymptomatic Adult ◽  
Upper Respiratory ◽  
Kinetics Of

Abstract Differential kinetics of RNA loads and infectious viral levels in the upper respiratory tract between asymptomatic and symptomatic SARS-CoV-2 infected adult outpatients remain unclear limiting recommendations that may guide clinical management, infection control measures and occupational health decisions. In the present investigation, 496 (2.5%) of 17,911 French adult outpatients were positive for an upper respiratory tract SARS-CoV-2 RNA detection by a quantitative RT-PCR assay, of which 180 (36.3%) were COVID-19 asymptomatic. Of these adult asymptomatic viral shedders, 84.4% had mean to high RNA viral loads (Ct values<30) which median value was significantly higher than that observed in symptomatic subjects (P=0.029), and 50.6% were positive by cell culture assays of their upper respiratory tract specimens. Our findings indicate that COVID-19 asymptomatic adult outpatients are significant viable SARS-CoV-2 shedders in their upper respiratory tract playing a major potential role as SARS-CoV-2 transmitters in various epidemiological transmission chains, promoting COVID-19 resurgence in populations.

scholarly journals Factors associated with the risk of upper respiratory tract bacterial infections among HIV-positive patients

2020 ◽  
Author(s):  
Agata Skrzat-Klapaczynska ◽  
Marcin Paciorek ◽  
Ewa Firlag-Burkacka ◽  
Andrzej Horban ◽  
Justyna Dominika Kowalska
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Bacterial Infections ◽  
Cd4 Count ◽  
Hiv Positive ◽  
Upper Respiratory Tract ◽  
Detectable Viral Load ◽  
Factors Associated ◽  
Multivariate Survival ◽  
Upper Respiratory

Background The risk and characteristics of upper respiratory tract (URT) bacterial infections (URT-BI) among HIV (+) patients is understudied. We analyzed factors associated with its occurrence and the spectrum of pathogens among patients routinely followed at the HIV Out-Patient Clinic in Warsaw. Methods All symptomatic HIV (+) patients with available URT swab culture were included into analyses. Patients were followed from the day of registration in the clinic until first positive URT swab culture or last clinical visit. Cox proportional hazard models were used to identify factors associated with positive URT swabs culture (those with p<0.1 in univariate included into multivariable). Results In total 474 patients were included into the analyses, 166 with positive URT swab. In general 416 (87.8%) patients were male, 342 (72.1%) were infected through MSM contact, 253 (53.4%) were on antiretroviral therapy. Median follow-up time was 3.4 (1.3-5.7) years, age 35.2 (30.6-42.6) years and CD4+ count 528 (400-685) cells/μl. The most common pathogens were S. aureus (40.4%) and S. pyogenes (13.9%) (Table 1). Patients with URT-BI were more likely to be MSM (68.5% vs 78.9%; p<0.016), have detectable viral load (20.9% vs 12.0%; p<0.0001) and CD4+ cell count <500 cells/μl (55.2% vs 39.0%; p=0.003) (Table 2). In multivariate survival analyses detectable viral load (HR3.13; 95%Cl: 2.34-4.19) and MSM (1.63;1.09-2.42) were increasing, but older age (0.63;0.58-0.69, per 5 years older) and higher CD4+ count (0.90;0.85-0.95, per 100 cells/μl) decreasing the risk of URT-BI (Table 2). Conclusions URT BI are common among HIV (+) positive patients with high CD4+ count. Similarly to general population most common patogens are S. aureus and S. pyogenes. Risk factors identified in multivariate survival analysis indicate that younger MSM patients with detectable HIV viral load are at highest risk. In clinical practice this group of patients requires special attention.

scholarly journals Reduced Pathogenicity of the SARS-CoV-2 Omicron Variant in Hamsters

2022 ◽  
Author(s):  
Katherine McMahan ◽  
Victoria Giffin ◽  
Lisa Tostanoski ◽  
Benjamin Chung ◽  
Mazuba Siamatu ◽  
...  
Keyword(s):  
Weight Loss ◽  
Respiratory Tract ◽  
Lung Parenchyma ◽  
Clinical Disease ◽  
Upper Respiratory Tract ◽  
Viral Loads ◽  
Syrian Golden Hamsters ◽  
The World ◽  
Pulmonary Pathology ◽  
Upper Respiratory

The SARS-CoV-2 Omicron (B.1.1.529) variant has proven highly transmissible and has outcompeted the Delta variant in many regions of the world. Early reports have also suggested that Omicron may result in less severe clinical disease in humans. Here we show that Omicron is less pathogenic than prior SARS-CoV-2 variants in Syrian golden hamsters. Infection of hamsters with the SARS-CoV-2 WA1/2020, Alpha, Beta, or Delta strains led to 4-10% weight loss by day 4 and 10-17% weight loss by day 6, as expected. In contrast, infection of hamsters with two different Omicron challenge stocks did not result in any detectable weight loss, even at high challenge doses. Omicron infection still led to substantial viral replication in both the upper and lower respiratory tracts and pulmonary pathology, but with a trend towards higher viral loads in nasal turbinates and lower viral loads in lung parenchyma compared with WA1/2020 infection. These data suggest that the SARS-CoV-2 Omicron variant may result in more robust upper respiratory tract infection but less severe lower respiratory tract clinical disease compared with prior SARS-CoV-2 variants.

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