scholarly journals Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020

2020 ◽  
Vol 25 (32) ◽  
Author(s):  
Anika Singanayagam ◽  
Monika Patel ◽  
Andre Charlett ◽  
Jamie Lopez Bernal ◽  
Vanessa Saliba ◽  
...  

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.

Author(s):  
Stéphanie Baggio ◽  
Arnaud G L’Huillier ◽  
Sabine Yerly ◽  
Mathilde Bellon ◽  
Noémie Wagner ◽  
...  

Abstract The factors that contribute to transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by children are unclear. We analyzed viral load at the time of diagnosis in 53 children and 352 adults with coronavirus disease 2019 (COVID-19) in the first 5 days post symptom onset. No significant differences in SARS-CoV-2 RNA loads were seen between children and adults.


2020 ◽  
Author(s):  
Islam Hamed ◽  
Nesreen Shaban ◽  
Marwan Nassar ◽  
Sam Love ◽  
Martin D Curran ◽  
...  

Introduction Samples for diagnostic tests for SARS-CoV-2 can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum or tracheal aspirate or broncho-alveolar lavage - BAL). Data from different testing sites indicates different rates of positivity. Reverse-transcriptase polymerase chain reaction (RT-PCR) allows for semi-quantitative estimates of viral load as time to crossing threshold (Ct) is inversely related to viral load. Objectives The objective of our study was to evaluate SARS-CoV2 RNA loads between paired nasopharyngeal (NP) and deep lung (endotracheal aspirate or BAL) samples from critically ill patients. Methods SARS-CoV-2 RT-PCR results were retrospectively reviewed for 51 critically ill patients from 5 intensive care units in 3 hospitals ; Addenbrookes Hospital Cambridge (3 units), Royal Papworth Cambridge (1 unit), and Royal Sunderland Hospital (1 unit). At the times when paired NP and deep lung samples were obtained, one patient had been on oxygen only, 6 patients on non-invasive ventilation, 18 patients on ECMO, and 26 patients mechanically ventilated. Results Results collected showed significant gradient between NP and deep lung viral loads. Median Ct value was 29 for NP samples and 24 for deep lung samples. Of 51 paired samples, 16 were negative (below limit of detection) on NP swabs but positive (above limit of detection) on deep lung sample, whilst 2 were negative on deep sample but positive on NP (both patients were on ECMO). Conclusions It has been suggested that whilst SARS-CoV1 tends to replicate in the lower respiratory tract, SARS-CoV2 replicates more vigorously in the upper respiratory tract. These data challenge that assumption. These data suggest that viral migration to, and proliferation in, the lower respiratory tract may be a key factor in the progression to critical illness and the development of severe acute respiratory syndrome (SARS). Factors which promote this migration should be examined for association with severe COVID-19. From a practical point of view, patients with suspected severe COVID-19 should have virological samples obtained from the lower respiratory tract where-ever possible, as upper respiratory samples have a significant negative rate.


Author(s):  
Muge Cevik ◽  
Matthew Tate ◽  
Oliver Lloyd ◽  
Alberto Enrico Maraolo ◽  
Jenna Schafers ◽  
...  

Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterise viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods: Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings: Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum was 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has detected live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion: Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titres are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding: No funding was received.


Author(s):  
Jiankang Zhao ◽  
Haibo Li ◽  
Hui Li ◽  
Qiaoling Wu ◽  
Ke Wu ◽  
...  

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.


Author(s):  
Stéphanie Baggio ◽  
Arnaud G L`Huillier ◽  
Sabine Yerly ◽  
Mathilde Bellon ◽  
Noémie Wagner ◽  
...  

The role of children in the transmission of SARS-CoV-2 is unclear. We analysed viral load at the time of diagnosis in 53 children vs. 352 adults with COVID-19 in the first 5 days post symptom onset. No significant differences in SARS-CoV-2 RNA loads were seen between children and adults.


2020 ◽  
Author(s):  
Agata Skrzat-Klapaczynska ◽  
Marcin Paciorek ◽  
Ewa Firlag-Burkacka ◽  
Andrzej Horban ◽  
Justyna Dominika Kowalska

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.


2021 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in upper respiratory tract leading to coronavirus disease 2019 (Covid-19). Severe Covid-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting entry of the virus or its internalization in the upper respiratory tract, are of interest. Herein, we report the prophylactic application of two intra-nasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and Til tailya in SARS-CoV2 infection hamster model. Prophylactic nasal instillation of these oil formulations exhibited reduced viral load in lungs, and resulted in reduced body weight loss and pneumonitis. In line with reduced viral load, histopathlogical analysis revealed a reduction in lung pathology in Anu oil group as compared to the control infected group. However, Til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokines genes, including Th1 and Th17 cytokines for both the intra-nasal formulations as a result of decreased viral load. Together, the prophylactic intra-nasal application of Annu oil seems to be useful in limiting both the viral load and disease severity disease in SARS-CoV2 infection in hamster model.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric C. Rouchka ◽  
Julia H. Chariker ◽  
Brian Alejandro ◽  
Robert S. Adcock ◽  
Richa Singhal ◽  
...  

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.


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