COVID-19 viral load not associated with disease severity: findings from a retrospective cohort study

Abstract Background Being able to use COVID-19 RT-PCR Ct values as simple clinical markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study’s objective was thus to explore whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices. Results A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain’s National COVID-19 Task force’s centralised database. The study period ranged from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p = 0.054). Conclusion Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder. As such, RT-PCR Ct values may not be a useful prognostic clinical tool in isolation.

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COVID-19 Viral Load Not Associated with Disease Severity: Findings from A Retrospective Cohort Study

10.21203/rs.3.rs-144590/v1 ◽

2021 ◽

Author(s):

Abdulkarim Abdulrahman ◽

Saad Mallah ◽

Manaf AlQahtani

Keyword(s):

Cohort Study ◽

Viral Load ◽

Disease Severity ◽

Odds Ratio ◽

Retrospective Cohort ◽

Statistical Significance ◽

Rt Pcr ◽

Cross Sectional ◽

Viral Loads ◽

Using Data

Abstract Background: Being able to use COVID-19 RT-PCR Ct values as simple markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study’s objective was thus to assess whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices Results: A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain’s National COVID-19 Task force’s centralised database. The study period was from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p=0.054). Conclusion: Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder.

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Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Diagnostics ◽

10.3390/diagnostics11061091 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1091

Author(s):

Ali A. Rabaan ◽

Raghavendra Tirupathi ◽

Anupam A Sule ◽

Jehad Aldali ◽

Abbas Al Mutair ◽

...

Keyword(s):

Viral Load ◽

Real Time ◽

Disease Severity ◽

False Negative ◽

Influential Factors ◽

Confirmatory Test ◽

Acid Extraction ◽

Rt Pcr ◽

Viral Kinetics ◽

Ct Value

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

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Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality

10.1101/2021.01.04.21249236 ◽

2021 ◽

Author(s):

Julio Silva ◽

Carolina Lucas ◽

Maria Sundaram ◽

Benjamin Israelow ◽

Patrick Wong ◽

...

Keyword(s):

Viral Load ◽

Disease Severity ◽

T Cell Subsets ◽

Temporal Association ◽

Strongly Correlated ◽

Immunological Parameters ◽

Viral Loads ◽

Patient Demographics ◽

Over Time

While several clinical and immunological parameters correlate with disease severity and mortality in SARS-CoV-2 infection, work remains in identifying unifying correlates of coronavirus disease 2019 (COVID-19) that can be used to guide clinical practice. Here, we examine saliva and nasopharyngeal (NP) viral load over time and correlate them with patient demographics, and cellular and immune profiling. We found that saliva viral load was significantly higher in those with COVID-19 risk factors; that it correlated with increasing levels of disease severity and showed a superior ability over nasopharyngeal viral load as a predictor of mortality over time (AUC=0.90). A comprehensive analysis of immune factors and cell subsets revealed strong predictors of high and low saliva viral load, which were associated with increased disease severity or better overall outcomes, respectively. Saliva viral load was positively associated with many known COVID-19 inflammatory markers such as IL-6, IL-18, IL-10, and CXCL10, as well as type 1 immune response cytokines. Higher saliva viral loads strongly correlated with the progressive depletion of platelets, lymphocytes, and effector T cell subsets including circulating follicular CD4 T cells (cTfh). Anti-spike (S) and anti-receptor binding domain (RBD) IgG levels were negatively correlated with saliva viral load showing a strong temporal association that could help distinguish severity and mortality in COVID-19. Finally, patients with fatal COVID-19 exhibited higher viral loads, which correlated with the depletion of cTfh cells, and lower production of anti-RBD and anti-S IgG levels. Together these results demonstrated that viral load – as measured by saliva but not nasopharyngeal — is a dynamic unifying correlate of disease presentation, severity, and mortality over time.

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A41 Deep sequencing of respiratory syncytial virus links viral diversity to disease severity

Virus Evolution ◽

10.1093/ve/vez002.040 ◽

2019 ◽

Vol 5 (Supplement_1) ◽

Author(s):

Inne Nauwelaers ◽

Tiina Talts ◽

Monica Galiano ◽

Peter Openshaw

Keyword(s):

Viral Load ◽

Respiratory Syncytial Virus ◽

Disease Severity ◽

Illumina Sequencing ◽

Likelihood Method ◽

Evolutionary Analysis ◽

Viral Loads ◽

Ct Value ◽

A Genome ◽

Syncytial Virus

Abstract Respiratory syncytial virus (RSV) is a common virus that can cause bronchiolitis in infants and pneumonia in immunocompromised and elderly people. RSV belongs to the Pneumoviridae family and consists of a genome of 15 kb. Its genome contains ten genes that code for eleven proteins, with M2 coding for two different proteins in overlapping open reading frames. It is unclear why some infected children have severe disease and others have mild or asymptomatic disease. In this project, methods for complete genome sequencing of RSV via Sanger and Illumina MiSeq platforms were optimized. One hundred and twenty-four community samples (59 RSV A and 65 RSV B) from 2014 to 2018 were collected (in collaboration with the Royal College of General Practitioners) and sequenced. Samples were selected based on viral load (e.g. Ct values had to be < 30). The genotype of each sample was determined by constructing phylogenetic trees with reference sequences from all genotypes. Trees were reconstructed using the maximum likelihood method. Furthermore, Illumina sequencing was used to deep sequence seven community samples and four hospital samples that were spatiotemporally matched (obtained via Imperial College NHS Trust hospitals). Variants were studied to investigate if certain variants influence disease severity (e.g. cause mild (community samples) or severe infection (hospital samples)). Analysis so far showed that ON1 (with a seventy-two nucleotide duplication in attachment protein G) is the most common genotype in both community and hospitalized samples (90% and 75% of samples, respectively), with GA2 (without duplication) as the next most common genotype for RSV A subtypes (7% and 25%). Three per cent of community samples were of the GA5 genotype. Samples from the RSV B subgroup all belong to the BA genotypes with a 60-nucleotide duplication in G. Samples that were selected for Illumina sequencing had a Ct value between 19.0 and 29.1, while hospital samples had a Ct value of 18.3 to 29.1. Viral load, therefore, did not explain disease severity in these selected samples. The Shannon entropy from Illumina sequenced samples averaged at 22.78 in community samples (ranges from 15 to 28) and 38.78 in hospitalized samples (ranges from 31 to 57). This indicated that diversity of the virus pool might influence disease severity; however, more samples need to be analyzed. There are no specific variants that could explain disease severity. Diversity of the virus pool could explain the link between higher viral loads and disease severity, which is sometimes found but cannot always be confirmed. Higher viral loads can harbor more diverse viral particles compared to lower viral loads. Future work will focus on more in-depth variation and diversity analysis and on evolutionary analysis of both community and hospital samples. We will also investigate intra-host evolution of RSV in acute infections using consecutive samples and its possible implications on the host response.

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Thrombocytopenia according to antiretroviral drug combinations, viremia and CD4 lymphocytes among HIV-infected patients in Cameroon: a snapshot from the City of Yaoundé

BMC Research Notes ◽

10.1186/s13104-019-4664-7 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 3

Author(s):

Alex Durand Nka ◽

Samuel Martin Sosso ◽

Joseph Fokam ◽

Yagai Bouba ◽

Georges Teto ◽

...

Keyword(s):

Viral Load ◽

Blood Platelets ◽

Undetectable Viral Load ◽

Drug Combinations ◽

People Living With Hiv ◽

Cross Sectional ◽

Viral Loads ◽

Reference Centre ◽

Antiretroviral Drug ◽

Load Rate

Abstract Objective Thrombocytopenia is an abnormal decrease in blood platelets, which can affect the prognosis of people living with HIV (PLHIV). In order to assess the burden of this haematological disorder, we evaluated the frequency of thrombocytopenia according to antiretroviral drug combinations, viremia and the immune status of PLHIV. Results A cross-sectional and analytical study was conducted from June to November 2016 among 310 PLHIV at the “Chantal BIYA” International Reference Centre, Yaoundé, Cameroon. Overall rate of thrombocytopenia was 19.0% (59/310). The rate of thrombocytopenia was 64.6% (42/65) versus 6.9% (17/245) in ART-naïve versus ART-treated patients respectively, p < 0.0001. Following viral load, rate of thrombocytopenia was 15.8% (20/130) in those with undetectable viral load, and 34.1% (27/79) with viral loads > 3 log10 RNA/ml (p = 0.03). As concerns CD4-count, rate of thrombocytopenia was 16.2% (42/259) in those with ≥ 200 CD4/mm3 versus 33.3% (17/51) with < 200 CD4/mm3 (p = 0.0003). After adjusting for sex, ART, viral load and CD4, Viral load and ART exposure were significantly associated with decreased risk of thrombocytopenia (p < 0.05). Thrombocytopenia occurs especially among ART-naïve, high viremia and severe immune-compromised patients. Interestingly, ART coverage appears as an independent factor in preventing the occurrence of thrombocytopenia.

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SARS-CoV-2 viral load is associated with increased disease severity and mortality

Nature Communications ◽

10.1038/s41467-020-19057-5 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 9

Author(s):

Jesse Fajnzylber ◽

◽

James Regan ◽

Kendyll Coxen ◽

Heather Corry ◽

...

Keyword(s):

Viral Load ◽

Disease Severity ◽

Diverse Range ◽

Viral Loads ◽

Mild Disease ◽

Reactive Protein ◽

Markers Of Inflammation ◽

Increased Risk ◽

Risk Of Disease ◽

Absolute Lymphocyte Counts

Abstract The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

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Factors Associated With Viral Load Kinetics of Middle East Respiratory Syndrome Coronavirus During the 2015 Outbreak in South Korea

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa466 ◽

2020 ◽

Author(s):

Jeong-Sun Yang ◽

Min-Gyu Yoo ◽

Hye-Ja Lee ◽

Han Byul Jang ◽

Hee-Dong Jung ◽

...

Keyword(s):

Viral Load ◽

Middle East ◽

Symptom Onset ◽

Healthcare Workers ◽

Middle East Respiratory Syndrome ◽

Viral Loads ◽

Hospitalization Period ◽

Using Data ◽

Kinetics Of ◽

Respiratory Specimens

Abstract We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4–10 days after symptom onset.

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Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study

BMJ ◽

10.1136/bmj.m1443 ◽

2020 ◽

pp. m1443 ◽

Cited By ~ 319

Author(s):

Shufa Zheng ◽

Jian Fan ◽

Fei Yu ◽

Baihuan Feng ◽

Bin Lou ◽

...

Keyword(s):

Viral Load ◽

Retrospective Cohort ◽

Severe Disease ◽

Zhejiang Province ◽

Serum Samples ◽

Viral Loads ◽

Mild Disease ◽

Stool Samples ◽

Serum And Urine ◽

Serum And Urine Samples

AbstractObjectiveTo evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China.DesignRetrospective cohort study.SettingA designated hospital for patients with covid-19 in Zhejiang province, China.Participants96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020.Main outcome measuresRibonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed.Results3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients.ConclusionThe duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.

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Comparison of SARS-CoV-2 antigen electrochemiluminescence immunoassay to RT-PCR assay for laboratory diagnosis of COVID-19 in Peshawar

Diagnosis ◽

10.1515/dx-2021-0078 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Bilal Iqbal ◽

Maria Khan ◽

Noman Shah ◽

Mirza Muhammad Dawood ◽

Valeed Jehanzeb ◽

...

Keyword(s):

Laboratory Diagnosis ◽

Cross Sectional Study ◽

Antigen Test ◽

Rt Pcr ◽

Pcr Assay ◽

Cross Sectional ◽

Viral Loads ◽

Testing Algorithms ◽

Frequent Testing ◽

Antigen Testing

Abstract Objectives Antigen based rapid diagnostic tests possesses a potential to be utilized along with Gold standard methods to detect Covid-19 infection to cope with the demand of testing. The aim of this study was to determine diagnostic accuracy of electrochemiluminescence based automated antigen detection immunoassay comparing with molecular based test RT-PCR (Covid-19). Methods It was a cross-sectional study conducted in RMI Peshawar, from 1st April 2021 till 30th April 2021. The study comprised 170 individuals who were suspected of having Covid-19. Nasopharyngeal samples taken from suspected individuals were analyzed by RT-PCR and automated antigen test (Elecsys SARS-CoV-2 Antigen) simultaneously. The correlation of SARS-CoV-2 antigen with PCR positive and negative cases was analyzed for specificity, sensitivity respectively. Results The ECLIA based Elecsys antigen test (Roche) revealed overall sensitivity 72%, specificity 95% and accuracy of 94.9%. Sensitivity of antigen test progressively declined from 94.3% in Ct <25 to 70.8% in Ct 26–29 and then to 47.2% in Ct 30–35. Conclusions Based on the findings of our study we conclude that automated antigen testing (Elecsys SARS-CoV-2 Antigen) cannot replace molecular based testing like RT PCR. Elecsys SARS-CoV-2 Ag test should be used complementary to RT-PCR in testing algorithms. Frequent testing strategy should be adopted while using automated antigen testing to overcome its limitation in individuals with low viral loads.

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

Scientific Reports ◽

10.1038/s41598-021-95197-y ◽

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.

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