Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients With Coronavirus Disease 2019

Abstract Background Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates. However, the impact of viral burden on these outcomes is unknown. Methods We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 30 March 2020 to 30 April 2020 at 2 hospitals in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared characteristics and outcomes of patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with intubation and in-hospital mortality. Results We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% (Ct <25; n = 220), 17.6% (Ct 25–30; n = 216), and 6.2% (Ct >30; n = 242) with high, medium, and low viral loads, respectively (P < .001). The risk of intubation was also higher in patients with a high viral load (29.1%) compared with those with a medium (20.8%) or low viral load (14.9%; P < .001). High viral load was independently associated with mortality (adjusted odds ratio [aOR], 6.05; 95% confidence interval [CI], 2.92–12.52) and intubation (aOR, 2.73; 95% CI, 1.68–4.44). Conclusions Admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlates with the risk of intubation and in-hospital mortality. Providing this information to clinicians could potentially be used to guide patient care.

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Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City

PLoS ONE ◽

10.1371/journal.pone.0257979 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0257979

Author(s):

Michael J. Satlin ◽

Jason Zucker ◽

Benjamin R. Baer ◽

Mangala Rajan ◽

Nathaniel Hupert ◽

...

Keyword(s):

Public Health ◽

New York ◽

New York City ◽

Viral Load ◽

Hospital Mortality ◽

York City ◽

Health Interventions ◽

Public Health Interventions ◽

Viral Loads ◽

The Impact

Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.

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SARS-CoV-2 Viral Load Is Correlated With the Disease Severity and Mortality in Patients With Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.715794 ◽

2021 ◽

Vol 11 ◽

Author(s):

Maha Al-Mozaini ◽

Abu Shadat M. Noman ◽

Jawaher Alotaibi ◽

Mohammed Rezaul Karim ◽

A. S. M. Zahed ◽

...

Keyword(s):

Viral Load ◽

Cancer Patients ◽

Disease Severity ◽

High Viral Load ◽

Attributable Mortality ◽

Nasopharyngeal Swab ◽

Viral Loads ◽

Hematologic Cancer ◽

Increased Risk ◽

Anticancer Treatment

The correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and risk of disease severity in cancer patients is poorly understood. Given the fact that cancer patients are at increased risk of severe coronavirus disease 2019 (COVID-19), analysis of viral load and disease outcome in COVID-19-infected cancer patients is needed. Here, we measured the SARS-CoV-2 viral load using qPCR cycle threshold (Ct) values collected from 120 noncancer and 64 cancer patients’ nasopharyngeal swab samples who are admitted to hospitals. Our results showed that the in-hospital mortality for high viral load cancer patients was 41.38%, 23.81% for medium viral load and 14.29% for low viral load patients (p < −0.01). On the other hand, the mortality rate for noncancer patients was lower: 22.22% among patients with high viral load, 5.13% among patients with medium viral load, and 1.85% among patients with low viral load (p < 0.05). In addition, patients with lung and hematologic cancer showed higher possibilities of severe events in proportion to high viral load. Higher attributable mortality and severity were directly proportional to high viral load particularly in patients who are receiving anticancer treatment. Importantly, we found that the incubation period and serial interval time is shorter in cancer patients compared with noncancer cases. Our report suggests that high SARS-CoV-2 viral loads may play a significant role in the overall mortality and severity of COVID-19-positive cancer patients, and this warrants further study to explore the disease pathogenesis and their use as prognostic tools.

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Pooled Saliva Specimens for SARS-CoV-2 Testing

Journal of Clinical Microbiology ◽

10.1128/jcm.02486-20 ◽

2020 ◽

Author(s):

Bidisha Barat ◽

Sanchita Das ◽

Valeria De Giorgi ◽

David K. Henderson ◽

Stacy Kopka ◽

...

Keyword(s):

Viral Load ◽

Screening Program ◽

High Viral Load ◽

Load Cycle ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Viral Loads ◽

Viral Transport ◽

Average Loss ◽

Positive Agreement

We evaluated saliva (SAL) specimens for SARS-CoV-2 RT-PCR testing by comparison of 459 prospectively paired nasopharyngeal (NP) or mid-turbinate (MT) swabs from 449 individuals with the aim of using saliva for asymptomatic screening. Samples were collected in a drive-through car line for symptomatic individuals (N=380) and in the emergency department (ED) (N=69). The percent positive and negative agreement of saliva compared to nasopharyngeal swab were 81.1% (95% CI: 65.8% – 90.5%) and 99.8% (95% CI: 98.7% – 100%), respectively. The percent positive agreement increased to 90.0% (95% CI: 74.4% – 96.5%) when considering only samples with moderate to high viral load (Cycle threshold (Ct) for the NP <=34). Pools of five saliva specimens were also evaluated on three platforms: bioMérieux NucliSENS easyMAG with ABI 7500Fast (CDC assay), Hologic Panther Fusion®, and Roche COBAS® 6800. The average loss of signal upon pooling was 2-3 Ct values across the platforms. The sensitivity of detecting a positive specimen in a pool compared with testing individually was 94%, 90%, and 94% for CDC 2019-nCoV Real-Time RT-PCR, Panther Fusion® SARS-CoV-2 assay, and cobas® SARS-CoV-2 test respectively, with decreased sample detection trending with lower viral load. We conclude that although pooled saliva testing, as collected in this study, is not quite as sensitive as NP/MT testing, saliva testing is adequate to detect individuals with higher viral loads in an asymptomatic screening program, does not require swabs or viral transport media for collection, and may help to improve voluntary screening compliance for those individuals averse to various forms of nasal collections.

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Pooled Saliva Specimens for SARS-CoV-2 Testing

10.1101/2020.10.02.20204859 ◽

2020 ◽

Author(s):

Bidisha Barat ◽

Sanchita Das ◽

Valeria De Giorgi ◽

David K. Henderson ◽

Stacy Kopka ◽

...

Keyword(s):

Viral Load ◽

Screening Program ◽

High Viral Load ◽

Load Cycle ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Lower Viral Load ◽

Viral Loads ◽

Viral Transport ◽

Positive Specimen

AbstractWe evaluated saliva (SAL) specimens for SARS-CoV-2 RT-PCR testing by comparison of 459 prospectively paired nasopharyngeal (NP) or mid-turbinate (MT) swabs from 449 individuals with the aim of using saliva for asymptomatic screening. Samples were collected in a drive-through car line for symptomatic individuals (N=380) and in the emergency department (ED) (N=69). The percent positive and negative agreement of saliva compared to nasopharyngeal swab were 81.1% (95% CI: 65.8% – 90.5%) and 99.8% (95% CI: 98.7% – 100%), respectively. The sensitivity increased to 90.0% (95% CI: 74.4% – 96.5%) when considering only samples with moderate to high viral load (Cycle threshold (Ct) for the NP <=34). Pools of five saliva specimens were also evaluated on three platforms: bioMérieux NucliSENS easyMAG with ABI 7500Fast (CDC assay), Hologic Panther Fusion, and Roche COBAS 6800. The median loss of signal upon pooling was 2-4 Ct values across the platforms. The sensitivity of detecting a positive specimen in a pool compared with testing individually was 100%, 93%, and 95% for CDC 2019-nCoV Real-Time RT-PCR, Panther Fusion® SARS-CoV-2 assay, and cobas® SARS-CoV-2 test respectively, with decreased sample detection trending with lower viral load. We conclude that although pooled saliva testing, as collected in this study, is not quite as sensitive as NP/MT testing, saliva testing is adequate to detect individuals with higher viral loads in an asymptomatic screening program, does not require swabs or viral transport media for collection, and may help to improve voluntary screening compliance for those individuals averse to various forms of nasal collections.

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Disease Severity and Prognosis of SARS-CoV-2 Infection in Hospitalized Patients Is Not Associated With Viral Load in Nasopharyngeal Swab

Frontiers in Medicine ◽

10.3389/fmed.2021.714221 ◽

2021 ◽

Vol 8 ◽

Author(s):

Elisabetta Cocconcelli ◽

Gioele Castelli ◽

Francesco Onelia ◽

Enrico Lavezzo ◽

Chiara Giraudo ◽

...

Keyword(s):

Viral Load ◽

Medical Care ◽

Disease Severity ◽

High Intensity ◽

Hospitalized Patients ◽

Nasopharyngeal Swab ◽

Asymptomatic Individuals ◽

The Right ◽

Asymptomatic Subjects ◽

The Impact

Background: The impact of viral burden on severity and prognosis of patients hospitalized for Coronavirus Disease 2019 (COVID-19) is still a matter of debate due to controversial results. Herein, we sought to assess viral load in the nasopharyngeal swab and its association with severity score indexes and prognostic parameters.Methods: We included 127 symptomatic patients and 21 asymptomatic subjects with a diagnosis of SARS-CoV-2 infection obtained by reverse transcription polymerase chain reaction and presence of cycle threshold. According to the level of care needed during hospitalization, the population was categorized as high-intensity (HIMC, n = 76) or low intensity medical care setting (LIMC, n = 51).Results: Viral load did not differ among asymptomatic, LIMC, and HIMC SARS-CoV-2 positive patients [4.4 (2.9–5.3) vs. 4.8 (3.6–6.1) vs. 4.6 (3.9–5.7) log10 copies/ml, respectively; p = 0.31]. Similar results were observed when asymptomatic individuals were compared to hospitalized patients [4.4 (2.9–5.3) vs. 4.68 (3.8–5.9) log10 copies/ml; p = 0.13]. When the study population was divided in High (HVL, n = 64) and Low Viral Load (LVL, n = 63) group no differences were observed in disease severity at diagnosis. Furthermore, LVL and HVL groups did not differ with regard to duration of hospital stay, number of bacterial co-infections, need for high-intensity medical care and number of deaths. The viral load was not an independent risk factor for HIMC in an adjusted multivariate regression model (OR: 1.59; 95% CI: 0.46–5.55, p = 0.46).Conclusions: Viral load at diagnosis is similar in asymptomatic and hospitalized patients and is not associated with either worse outcomes during hospitalization. SARS CoV-2 viral load might not be the right tool to assist clinicians in risk-stratifying hospitalized patients.

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SARS-CoV-2 infection: Initial viral load (iVL) predicts severity of illness/outcome, and declining trend of iVL in hospitalized patients corresponds with slowing of the pandemic

PLoS ONE ◽

10.1371/journal.pone.0255981 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0255981

Author(s):

Said El Zein ◽

Omar Chehab ◽

Amjad Kanj ◽

Sandy Akrawe ◽

Samer Alkassis ◽

...

Keyword(s):

Viral Load ◽

Hospital Mortality ◽

Prognostic Marker ◽

Independent Predictor ◽

Population Level ◽

Hospitalized Patients ◽

Respiratory Syndrome Virus ◽

Nasopharyngeal Swab ◽

Ct Value ◽

Increased Risk

Background Hospitalization of patients infected with the severe acute respiratory syndrome virus 2 (SARS-CoV-2) have remained considerable worldwide. Patients often develop severe complications and have high mortality rates. The cycle threshold (Ct) value derived from nasopharyngeal swab samples using real time polymerase chain reaction (RT-PCR) may be a useful prognostic marker in hospitalized patients with SARS-CoV-2 infection, however, its role in predicting the course of the pandemic has not been evaluated thus far. Methods We conducted a retrospective cohort study which included all patients who had a nasopharyngeal sample positive for SARS-CoV-2 between April 4 –June 5, 2020. The Ct value was used to estimate the number of viral particles in a patient sample. The trend in initial viral load on admission on a population level was evaluated. Moreover, patient characteristics and outcomes stratified by viral load categories were compared and initial viral load was assessed as an independent predictor of intubation and in-hospital mortality. Results A total of 461 hospitalized patients met the inclusion criteria. This study consisted predominantly of acutely infected patients with a median of 4 days since symptom onset to PCR. As the severity of the pandemic eased, there was an increase in the percentage of samples in the low initial viral load category, coinciding with a decrease in deaths. Compared to an initial low viral load, a high initial viral load was an independent predictor of in-hospital mortality (OR 5.5, CI 3.1–9.7, p < 0.001) and intubation (OR 1.82 CI 1.07–3.11, p = 0.03), while an initial intermediate viral load was associated with increased risk of inpatient mortality (OR 1.9, CI 1.14–3.21, p = 0.015) but not with increased risk for intubation. Conclusion The Ct value obtained from nasopharyngeal samples of hospitalized patients on admission may serve as a prognostic marker at an individual level and may help predict the course of the pandemic when evaluated at a population level.

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Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study

BMJ ◽

10.1136/bmj.n1637 ◽

2021 ◽

pp. n1637 ◽

Cited By ~ 1

Author(s):

Marta García-Fiñana ◽

David M Hughes ◽

Christopher P Cheyne ◽

Girvan Burnside ◽

Mark Stockbridge ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Viral Load ◽

Predictive Value ◽

High Viral Load ◽

Test Results ◽

Chain Reaction ◽

Viral Loads ◽

Flow Test ◽

Polymerase Chain ◽

Lateral Flow Test

Abstract Objective To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres. Design Observational cohort study. Setting Community LFT pilot at covid-19 testing sites in Liverpool, UK. Participants 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020. Interventions Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites. Main outcome measures Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease. Results Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >10 6 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>10 4 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<10 4 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. Conclusions The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.

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SARS-CoV-2 Persistence in Immunocompromised Children

10.22541/au.162448803.31733691/v1 ◽

2021 ◽

Author(s):

Susan Dolan ◽

Jean Mulcahy Levy ◽

Angla Moss ◽

Kelly Pearce ◽

Samuel Dominguez ◽

...

Keyword(s):

Viral Load ◽

Median Time ◽

Immunosuppressive Treatment ◽

Viral Persistence ◽

High Viral Load ◽

Viral Loads ◽

Mild Disease ◽

Kaplan Meier ◽

Diagnostic Panel ◽

Event Times

Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of <30, (moderate to high viral load); 4 children had CT values of <30 3-4 weeks later, suggesting persistent moderate to high viral loads. Conclusions: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.

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The high volume of patients admitted during the SARS-CoV-2 pandemic has an independent harmful impact on in-hospital mortality from COVID-19

PLoS ONE ◽

10.1371/journal.pone.0246170 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0246170

Author(s):

Alessandro Soria ◽

Stefania Galimberti ◽

Giuseppe Lapadula ◽

Francesca Visco ◽

Agata Ardini ◽

...

Keyword(s):

Hospital Mortality ◽

High Volume ◽

Hospitalized Patients ◽

Urgent Care ◽

Calendar Period ◽

Cox Models ◽

Hospital System ◽

Risk Of Death ◽

The Impact ◽

Age And Sex

Background During the Coronavirus disease 2019 (COVID-19) pandemic, advanced health systems have come under pressure by the unprecedented high volume of patients needing urgent care. The impact on mortality of this “patients’ burden” has not been determined. Methods and findings Through retrieval of administrative data from a large referral hospital of Northern Italy, we determined Aalen-Johansen cumulative incidence curves to describe the in-hospital mortality, stratified by fixed covariates. Age- and sex-adjusted Cox models were used to quantify the effect on mortality of variables deemed to reflect the stress on the hospital system, namely the time-dependent number of daily admissions and of total hospitalized patients, and the calendar period. Of the 1225 subjects hospitalized for COVID-19 between February 20 and May 13, 283 died (30-day mortality rate 24%) after a median follow-up of 14 days (interquartile range 5–19). Hospitalizations increased progressively until a peak of 465 subjects on March 26, then declined. The risk of death, adjusted for age and sex, increased for a higher number of daily admissions (adjusted hazard ratio [AHR] per an incremental daily admission of 10 patients: 1.13, 95% Confidence Intervals [CI] 1.05–1.22, p = 0.0014), and for a higher total number of hospitalized patients (AHR per an increase of 50 patients in the total number of hospitalized subjects: 1.11, 95%CI 1.04–1.17, p = 0.0004), while was lower for the calendar period after the peak (AHR 0.56, 95%CI 0.43–0.72, p<0.0001). A validation was conducted on a dataset from another hospital where 500 subjects were hospitalized for COVID-19 in the same period. Figures were consistent in terms of impact of daily admissions, daily census, and calendar period on in-hospital mortality. Conclusions The pressure of a high volume of severely ill patients suffering from COVID-19 has a measurable independent impact on in-hospital mortality.

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Evaluation of saliva sampling procedures for SARS-CoV-2 diagnostics reveals differential sensitivity and association with viral load

10.1101/2020.10.06.20207902 ◽

2020 ◽

Author(s):

Pieter Mestdagh ◽

Michel Gillard ◽

Marc Arbyn ◽

Jean-Paul Pirnay ◽

Jeroen Poels ◽

...

Keyword(s):

Viral Load ◽

High Risk ◽

Health Professionals ◽

High Viral Load ◽

Sampling Procedure ◽

Differential Sensitivity ◽

Collection Method ◽

Viral Loads ◽

Saliva Collection ◽

Sampling Procedures

AbstractNasopharyngeal sampling has been the preferential collection method for SARS-CoV-2 diagnostics. Alternative sampling procedures that are less invasive and do not require a healthcare professional would be more preferable for patients and health professionals. Saliva collection has been proposed as such a possible alternative sampling procedure. We evaluated the sensitivity of SARS-CoV-2 testing on two different saliva collection devices (spitting versus swabbing) compared to nasopharyngeal swabs in over 2500 individuals that were either symptomatic or had high-risk contacts with infected individuals. We observed an overall poor sensitivity in saliva for SARS-CoV-2 detection (30.8% and 22.4% for spitting and swabbing, respectively). However, when focusing on individuals with medium to high viral load, sensitivity increased substantially (97.0% and 76.7% for spitting and swabbing, respectively), irrespective of symptomatic status. Our results suggest that saliva cannot readily replace nasopharyngeal sampling for SARS-CoV-2 diagnostics but may enable identification of cases with medium to high viral loads.

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