Systematic Reviews
Copyright ©The Author(s) 2021.
World J Crit Care Med. Jul 9, 2021; 10(4): 132-150
Published online Jul 9, 2021. doi: 10.5492/wjccm.v10.i4.132
Table 1 Manuscript evaluating quantitative viral load assay and coronavirus disease 2019 outcomes. Sixty manuscripts meet the inclusion criteria
Ref./country
Number of patients
Age (yr)
Sampled sites
Quantitative viral load reported as Ct values or Log10 copies /mL /RTPCR gene target
Correlation with severity of sepsis
Correlation with mortality
P value
Merits of the study/key points
He et al[1], China94Median 47 yrNasopharynxCt values/; N geneNot reportedNot reportedNRHighest viral load at pre-symptomatic stage and infectiousness peaks before symptom onset.
Xu et al[2], China51Median 37 yrNasopharynx, BAL, Anal swabCt values/; ORF1ab and N geneNoNo> 0.05The quantitative viral load and infectiousness may be the similar for primary (imported form epicenter) and secondary and tertiary exposed group of patients but decrease rapidly (in 14 d) in tertiary patients.
Lescure et al[3], France5Median 46 yrNasopharynx, Stool, PlasmaLog10copies/mL; RdRp-IP1 gene, E geneNoInadequate sample sizeNRPresymptomatic patients may have a high viral load and be highly infectious.
Liu et al[4], China76Median 50 yrNasopharynxCt values; Gene not reportedYesNo< 0.005Patients with severe COVID-19 have a higher mean viral load (60 times higher) and long shedding period.
To et al[5], China23Median 62 yrOropharynxLog10copies/mL/; RdRp geneYesNot reported0.56Peak viral load occurs at onset of symptoms and is correlated with increasing age and severity although not statistically significant.
Shen et al[6], China5Median 60 yrNasopharynxCt values; Gene not reportedYesNoNRPatients with severe sepsis and high quantitative viral load benefit from convalescent plasma. The viral load became negative in all 5 patients in 12 d with clinical improvement.
Duan et al[7], China10Median 52.5 yrNasopharynxCt values; ORF1ab and N geneYesNo< 0.001Resolution of severe sepsis and negative viral load with convalescent plasma infusion.
Chen et al[8], China48Median 63 yrOropharynx. serumCt values; ORF1ab and N geneYesYes< 0.001Serum viremia and viral load associated with severity and poor prognosis. High RNAaemia is associated with elevated IL-6 levels.
Pan et al[9], China82Not reportedOropharynx. Sputum, Stool Log10copies/mL; N geneYesYesNRViral load is high on presentation. Stool samples may turn positive later in the disease.
Cao et al[10], China199Median 58 yrOropharynxLog10copies/mL; N and E geneNot reportedNoNRLopinavir-Ritonavir did not aid with clinical improvement, reduce mortality or reduce the viral loads.
Wang et al[11], China237Median 65 yrOropharynx, SputumLog10copies/mL; Gene not reportedNot reportedNot reportedNRRemdesivir group does not decrease viral load compared to control group, however it may have faster time to clinical improvement.
Zou et al[12], China18Median 59 yrNasopharynx, OropharynxCt values; ORF1bNot reportedNot reportedNRHigh viral load begins in the presymptomatic period and may suggest high infectivity.
Wang et al[13], China 23Median 56 yrNasopharynx, Oropharynx, sputum, fecal, urine, plasmaCt values; RdRp and N geneYesNone< 0.001High viral load and shedding from multiple tissues occurs for a prolonged period in severe cases. Feces remains positive for a prolonged time.
Wölfel et al[14], Germany9Not reportedOropharynx, Sputum, stool, serum, urineLog10copies/mL; RdRp and E geneNoNoNRHigh viral load begins in the presymptomatic period and may continue beyond 10 d after symptoms ensue suggest high infectivity. No positivity in stool, urine or serum. All cases were with mild symptoms.
Zheng et al[15], China96Median 55 yrNasopharynx, Oropharynx, sputum, fecal, urine, plasmaCt values and Log10copies/mL; ORF1abYesNot reported0.03High respiratory viral load associated with disease severity and serum positivity and stool shedding occurs later and persists for a longer period.
Baggio et al[16], Swiss352 adults, 53 childrenMean 36.5 yrNasopharynxLog10copies/mL; ORF1ab and E geneNot reportedNot reportedNRChildren and adults can have same variation of viral loads, but risk of transmission and lower susceptibility in children may have other contributing factors.
Shi et al[17], China114Median 43.5yrOropharynx, serumLog10copies/mL; N geneYesNot reported< 0.001High viral loads associated with severe sepsis in female patients.
Clementi et al[18], Italy200Mean 64 yrNasopharynxCt values; ORF1ab and E geneYesNot reported0.08Higher viral loads associated with older age group and severity of sepsis.
Kwon et al[19], Korea31Mean 50 yrNasopharynxCt values; RdRp and N geneYesNone0.093High viral loads correlated with elevated cytokine profile and severity of sepsis.
Yu et al[20], China92Mean 55 yrSputumCt values/N and ORF1bYesNo0.017Higher baseline sputum viral load on admission is associated with severe disease.
Liu et al[21], China31Median 58 yrNasopharynx, sputumCt values; ORF1ab and N geneNot reportedNot reportedNRViral load is higher in deep sputum samples and have a higher shedding and transmission capacity.
Zhou et al[22], China31Median 41 yrNasopharynxCt values; ORF1ab and N geneNoNoNRAsymptomatic patients have high viral loads and continue viral shedding and transmission.
Cheung et al[23],Hong Kong59Median 58.5 yrStoolLog10copies/mL; Gene not reportedNoNo= 0.019Stool viral loads are higher in patients with diarrhea and may persist after negative respiratory specimens.
Azzi et al[24], Italy25Mean 61.5 yrSalivaCt values; 5’UTRYesNot reported= 0.04High salivary viral loads may be associated with severe disease and may persist after the negative respiratory specimens. High viral load associated with high serum LDH suggestive of tissue damage.
Chen et al[25], China22Median 36.5 yrSaliva, feces, OropharynxCt values; ORF1ab and N geneNoNoNRSputum and stool viral load remains positive after pharyngeal samples turn negative. Indicating the infectivity may persist after negative pharyngeal samples.
Huang et al[26], China16Median 59.5 yrNasopharynx, sputum, tracheal aspirates, fecal, urine, plasmaCt values; N geneYesNo< 0.01In severe cases higher viral load is demonstrated in deep sputum and tracheal aspirates compared to upper respiratory tract specimens.
Pujadas et al[27], United States1145Mean 64.6 yrNasopharynxLog10copies/mL; RdRp and N geneYesYes= 0.003High viral load is an independent predictor of mortality.
Arons et al[28], United States57Mean 75 yrNasopharynx, OropharynxCt values; N1 and N2NoNot reportedNRHigh viral loads demonstrated in presymptomatic, asymptomatic cases, favoring high transmissibility in close knit nursing home population.
Huang et al[29], China308Median 63 yrNasopharynx, OropharynxCt values; ORF1abYesYes< 0.001High viral load associated with critical disease and mortality. Sputum samples have higher viral loads.
Magleby et al[30], United States678Median 69 yrNasopharynx,Ct values; ORF1b and E geneYesYes< 0.001High viral load is an independent risk factor for severe sepsis, intubation and death.
Park et al[31], Korea46Median 26 yrNasopharynx, Oropharynx, sputum , StoolCt values; RdRp, N and E geneNoNoNRHigh fecal viral load and shedding, follows and persists after respiratory symptoms resolve for up to 50 d.
Yu et al[32], China76Median 40 yrNasopharynx, Oropharynx, sputum, urine, plasmaCt values; ORF1b and N geneYesNone< 0.001Digital droplet PCR is superior for patients with high suspicion but negative RTPCR. High viral load correlated with risk for progression and disease activity.
Blot et al[33], France14Median 67 yrBroncho-alveolar fluidLog10copies/mL; RdRpYesNot reported= 0.013Higher viral load associated with worse sepsis related organ failure (SOFA) scores.
Kim et al[34], Korea13Median 30 yrNasopharynxCt values; RdRp and E geneNoNoNRPatient with mild or asymptomatic infections are infectious before symptoms appear and 14 d of isolation may be sufficient in asymptomatic carriers.
Argyropoulos et al[35], United States205Median 60 yrNasopharynxLog10copies/mL; RdRp and N geneDecreasedDecreased< 0.001Study shows inverse correlation of high viral load with duration, severity of sepsis and no correlation with survival.
Xu et al[36], China85Median 56 yrNasopharynx, Oropharynx, serumCt values; ORF1b and N geneYesYes< 0.001Detection of high serum viral load in the serum increases the severity of organ damage, sepsis and mortality.
Veyer et al[37], France58Median 55.1 yr PlasmaLog10copies/mL; ORF1b and N geneYesYes= 0.036Detection of high Viral load in the serum increases the severity of sepsis and mortality.
Lin et al[38], China217Median 50 yrNasopharynx, Oropharynx, analCt values; ORF1b and N geneYesNo= 0.006Anal viral load remains positive longer and is correlated with severity of sepsis and ICU admission.
Wang et al[39], China275Median 49 yrOropharynxCt values; ORF1b and N geneNoNo= 0.824Similar viral loads between severe and mild cases, no correlation of viral load to ICU admission, severity or mortality.
Kimball et al[40], United States23Mean 80.7 yrNasopharynx, OropharynxCt values; N1, N2 genesNoNo= 0.3High viral loads in unrecognized asymptomatic and presymptomatic patients may contribute to infectiousness and transmission.
Schwierzeck et al[41] ,Germany12Not reportedNasopharynxCt values; E and RdRp genesYesNo= 0.007High viral load, 200 times greater in symptomatic patients compared to asymptomatic patients.
Xia et al[42], China10Mean 56.5 yrNasopharynxCt values; ORF1ab and N geneYesNoNRHigher viral load associated with severe symptoms and increased neutrophil/lymphocyte ratio.
Huang et al[43], China41Median 49 yrNasopharynx, Oropharynx, sputum, BALCt values; 5’UTRNoNoNoPatients with high viral load with RNAeamia had severe infection, elevated cytokine levels, and mortality but not statistically significant.
Hagman et al[44], Sweden167Median 63Nasopharynx, Oropharynx, sputum, BloodCt values; E, RdRp, ORF1 genesYesYesP < 0.05Viral RNAemia on admission was associated with eight fold increased risk of in hospital death.
Prebensen et al[45], Norway123Median 64Nasopharynx, Oropharynx, sputum, BloodCt values for respiratory specimens; Log10copies/mL for plasma samples; E geneYesYes< 0.001Higher viral loads associated with ICU admission and death.
Hasanoglu et al[46], Turkey60Mean 32Nasopharynx, Oropharynx, sputum, urine, Blood, rectalCt values; RdRp geneDecreasedDecreased= 0.0141Viral loads in younger asymptomatic patients were significantly higher compared to elderly, symptomatic patients.
Kawasuji et al[47], Japan28Median 45NasopharynxLog10copies/mL; N geneNoNo= 0.015High admission nasopharyngeal viral load associated with increased risk of transmission.
Bermejo-Martin et al[48], Spain250Median 66Nasopharynx, Oropharynx, sputum, urine, Blood, rectalLog10copies/mL; N geneYesYes< 0.001Increased serum viral load associated with increased severity, mortality and dysregulated host response.
Shlomai et al[49], Israel170Median 62NasopharynxCt values; N geneYesYes< 0.0001Increased hypoxemia, severity and eight fold increase in mortality.
Ra et al[50], Korea213Median 25NasopharynxCT value; E, N, RdRp geneNoNoNoneComparable viral load in asymptomatic and symptomatic patients, asymptomatic patients contribute to ongoing transmission.
Faico-Filho et al[51], Brazil875Median 48NasopharynxCt value; N geneYesYes< 0.0001Admission nasopharyngeal viral load was independently associated with increased mortality.
Chen et al[52], China52Median 62Blood, oropharynxLog10copies/mL; ORF1abYesYes< 0.001Increased RNAemia associated with severity, markers of inflammation and mortality.
Fajnzylber et al[53], United States88Median 57Nasopharynx, Oropharynx, sputum, BloodLog10copies/mL; N geneYesYes= 0.009Increased viremia associated with severity, progression and mortality.
Zhou et al[54], China195Median 66OropharynxCt value; N gene, ORF1abYesYes< 0.005High viral load associated with multi organ failure and death.
Maltezou et al[55], Greece1122Mean 46Nasopharynx, OropharynxCT value; E, RdRp geneYesYes< 0.05High viral load correlated with intubation and in hospital mortality.
Bitker et al[56], France129Median 69Nasopharynx, Oropharynx, sputumCt value; ORF1abYesYes< 0.05High viral load associated with increased mortality.
Carrasquer et al[57], Spain169Median 67NasopharynxCt value; E, N gene, ORF1abNoNo= 0.029High viral load statistically not associated with in hospital mortality.
de la Calle et al[58], Spain455Mean 64NasopharynxCt value; N geneYesYes= 0.022High viral load associated with respiratory failure, and 30 d mortality.
Bryan et al[59], United States109Mean 65NasopharynxCt value; N geneYesYes= 0.01The high nasopharyngeal viral load on admission was independently associated with greater mortality.
Choudhuri et al[60], United States1044Mean 65NasopharynxCt value; ORF1abNoYes< 0.001High viral load is an independent predictor of increased mortality.