Impact of viral load at admission on the development of respiratory failure in hospitalized patients with SARS-CoV-2 infection

Calle, C. de la; Lalueza, Antonio; Mancheño‐Losa, Mikel; Calle, Guillermo Maestro‐de la; Lora‐Tamayo, Jaime; Arrieta, Estíbaliz; García‐Reyne, Ana; Losada, Irene; Miguel, Borja de; Díaz-Simón, Raquel; López‐Medrano, Francisco; Carretero, Octavio; Juan, Rafael San; Aguado, José María; Lumbreras, Carlos

doi:10.1007/s10096-020-04150-w

Cited by 46 publications

(47 citation statements)

References 27 publications

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“…In contrast, studies where a positive association between nasopharyngeal SARS-CoV-2 Ct values and COVID-19 severity or outcomes was detailed are flourishing [6,7,[9][10][11][12]17,34,35]. Most of them included samples of more than 100 individuals with the reference swab represented by the diagnostic one, despite only two reported the time between disease onset and swab collection [7,17].…”

Section: Discussionmentioning

confidence: 99%

“…Further to the recognized risk factors for severity, the initial prognostic workup of persons infected by SARS-CoV-2 would also benefit from viral biomarkers able to predict COVID-19 evolution. In this regard, it is a current matter of debate whether SARS-CoV-2 viral load is an impactful factor in determining disease outcomes [6][7][8][9][10][11][12][13][14][15][16][17]. Previous evidence from SARS-CoV and influenza suggests that the higher the initial viral load, the worse the clinical evolution [18,19].…”

Section: Introductionmentioning

confidence: 99%

“…Previous evidence from SARS-CoV and influenza suggests that the higher the initial viral load, the worse the clinical evolution [18,19]. To date, few studies have investigated the relationships among SARS-CoV-2 viral load (usually measured by the proxy PCR cycle threshold value, Ct), and mortality, disease progression, and overall severity [7][8][9][10][11][12][13][14][15]17]. Current data point towards a plausible positive correlation between the amount of detected virus and the degree of SARS-CoV-2 pneumonia severity, hypoxemia intensity, risk of death, as well as of hematological, biochemical, and inflammatory alterations [6,[9][10][11][12]17,20,21].…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

Trunfio

Venuti

Alladio

et al. 2021

Viruses

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To date, there is no severe acute respiratory syndrome coronavirus 2- (SARS-CoV-2)-specific prognostic biomarker available. We assessed whether SARS-CoV-2 cycle threshold (Ct) value at diagnosis could predict novel CoronaVirus Disease 2019 (COVID-19) severity, clinical manifestations, and six-month sequelae. Hospitalized and outpatient cases were randomly sampled from the diagnoses of March 2020 and data collected at 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasopharyngeal swab at diagnosis as follows: Group A ≤20.0, 20.0< group B ≤28.0, and Group C >28.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required, and survival. Two hundred patients were included, 27.5% in Groups A and B both, 45.0% in Group C; 90% of patients were symptomatic and 63.7% were hospitalized. The median time from COVID-19 onset to swab collection was five days. Lethality, disease severity, type, and number of signs and symptoms, as well as six-month sequelae distributed inversely among the groups with respect to SARS-CoV-2 Ct. After controlling for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p = 0.023), disease severity (p = 0.023), number of signs and symptoms (p < 0.01), and presence of six-month sequelae (p < 0.01). Early quantification of SARS-CoV-2 may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

Trunfio

Venuti

Alladio

et al. 2021

Viruses

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“…Secondly, confusion surrounds the terminology used by studies assessing COVID-19 severity and the amount of virus at diagnosis. Once again, what has been found to predict COVID-19 severity is not the viral inoculum but the amount of virus that is locally replicating since at least few days before detection, as the shorter median period from disease onset to swab collection among the studies is 5 days (de la Calle et al, 2021;Trunfio et al, 2021). No evidence is yet available on the quantitative change from the amount of the viral inoculum to the amount of detected virus at symptom onset nor at diagnosis to support or reject this hypothesis, but the epistemological difference is substantial.…”

Section: Viral Replication Cut-offmentioning

confidence: 98%

On the SARS-CoV-2 “Variolation Hypothesis”: No Association Between Viral Load of Index Cases and COVID-19 Severity of Secondary Cases

et al. 2021

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Background: Emerging evidence supports the “variolation hypothesis” in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), but the derivative idea that the viral load of index cases may predict disease severity in secondary cases could be unsubstantiated. We assessed whether the prevalence of symptomatic infections, hospitalization, and deaths in household contacts of 2019 novel coronavirus disease (COVID-19) cases differed according to the SARS-CoV-2 PCR cycle threshold (Ct) from nasal-pharyngeal swab at diagnosis of linked index cases.Methods: Cross-sectional study on household contacts of COVID-19 cases randomly sampled from all the infections diagnosed in March at our Microbiology Laboratory (Amedeo di Savoia, Turin). Data were retrospectively collected by phone interviews and from the Piedmont regional platform for COVID-19 emergency. Index cases were classified as high (HVl) and low viral load (LVl) according to two exploratory cut-offs of RdRp gene Ct value. Secondary cases were defined as swab confirmed or symptom based likely when not tested but presenting compatible clinical picture.Results: One hundred thirty-two index cases of whom 87.9% symptomatic and 289 household contacts were included. The latter were male and Caucasian in 44.3 and 95.8% of cases, with a median age of 34 years (19–57). Seventy-four were swab confirmed and other 28 were symptom based likely secondary cases. Considering both, the contacts of HVl and LVl did not differ in the prevalence of symptomatic infections nor COVID-19-related hospitalization and death. No difference in median Ct of index cases between symptomatic and asymptomatic, hospitalized and not hospitalized, or deceased and survived secondary cases was found. Negative findings were confirmed after adjusting for differences in time between COVID-19 onset and swab collection of index cases (median 5 days) and after removing pediatric secondary cases.Conclusions: The amount of SARS-CoV-2 of the source at diagnosis does not predict clinical outcomes of linked secondary cases. Considering the impelling release of assays for SARS-CoV-2 RNA exact quantification, these negative findings should inform clinical and public health strategies on how to interpret and use the data.

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“…In this regard, different studies have addressed the possible association between the viral load in nasopharyngeal (NP) swabs and the clinical outcomes. Some studies have reported that a high number of virus copies in NP swabs, mainly defined as a cycle threshold (Ct) < 25 or < 22 in the real-time polymerase chain reaction (RT-PCR), was an independent risk factor for intubation and/or death 8 – 11 . However, other studies have not found independent association between low Ct values and critical care admission or death 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

Salto‐Alejandre

Berastegui‐Cabrera

Camacho‐Martínez

et al. 2021

Sci Rep

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The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.

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Impact of viral load at admission on the development of respiratory failure in hospitalized patients with SARS-CoV-2 infection

Cited by 46 publications

References 27 publications

Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

On the SARS-CoV-2 “Variolation Hypothesis”: No Association Between Viral Load of Index Cases and COVID-19 Severity of Secondary Cases

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

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