SARS-CoV-2 viral load in the upper respiratory tract and disease severity in COVID-19 patients

Table 1 Severe acute respiratory syndrome coronavirus 2 viral load and disease severity in coronavirus disease 2019 patients

Ref.	Study design	No. of COVID-19 cases	Median/mean viral load (Ct or Cq) (log10 copies/mL)	Association with disease severity	Conclusion
Knudtzen et al[17], Denmark	Prospective cohort	169 (87 OP/82 IP)	24.8 vs 28.1 (Severe vs Moderate)	Yes	Lower Cq-values were found to be indicative of more disease severity in hospitalized patients
Kawasuji et al[18], Japan	Retrospective cohort	56 (56 IP)	5.4 vs 2.6 (Critical/Moderate-Severe)	Yes	The viral loads of NP swabs were correlated with disease severity and death
Maltezou et al[19], Greece	Prospective cohort	1122 (274 OP/848 IP)	N/A	Yes	The viral load in the nasopharynx might be utilized to identify patients at increased risk for morbidity or poor outcome
Zheng et al[20], China	Retrospective cohort	96 (96 IP)	N/A	Yes	The virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease
Aydin et al[21], Turkey	Prospective cohort	300 (168/79/29/24)(M/I/S/C)	25.30/19.85/16.75/15.48 (M/I/S/C)	Yes	The Ct-values of saliva and oro-nasopharyngeal swab were useful in predicting disease severity
de la Calle et al[14], Spain	Retrospective cohort	455 (455 IP)	N/A	Yes	The Ct value of RT-PCR in nasopharyngeal swabs on admission is a useful predictive marker for the development of respiratory failure
Kwon et al[22], Korea	Prospective cohort	31 (31 IP)	35.2/27.9/26.7 (M/I/S+C)	Yes	High viral load in the respiratory tract and excessive cytokines and chemokines were substantially linked with the severity of COVID-19
Piubelli et al[23], Italy	Retrospective study	373 (373 OP)	N/A	Yes	The decreasing viral load that they observed during March to May 2020 was associated with a significant reduction in severe COVID-19 cases that needed intensive care
Shlomai et al[13], Israel	Retrospective cohort	170 (149 NS/21 SV)	23.43 vs 29.55 (NS vs SV)	Yes	There was a clear relationship between nasopharyngeal viral load and hypoxemia, as well as worse clinical outcomes in hospitalized COVID-19 patients
Soria et al[24], Spain	Prospective cohort	448 (110/236/102) (M/I/S)	35.75/32.69/29.58 (M/I/S)	Yes	The link between viral load and disease severity was shown in COVID-19 patients
Trunfio et al[25], Italy	Retrospective cohort	200 (32 NS/168 SV)	N/A	Yes	The Ct value detected within the first week of COVID-19 onset was associated with deaths and disease severity
Tsukagoshi et al[26], Japan	Retrospective study	286 (138 AS/133 SM/15 FT)	N/A	Yes	The high viral load in elderly patients at an early stage of the disease results in a bad prognosis
Wang et al[27], China	Prospective cohort	23 (11/12)(M/S)	N/A	Yes	The viral loads in the respiratory samples were larger in the severe group than in the mild group, and they gradually decreased with time
Faíco-Filho et al[28], Brazil	Retrospective cohort	875 (439/266/170)(M/I/S)	22/27/21.5 (M/I/S)	Yes	The SARS-CoV-2 virus load at admission was independently linked with death among hospitalized COVID-19 patients
Pérez-García et al[29], Spain	Retrospective study	255 (85/87/83) (M/I/S)	N/A	Yes	The SARS-CoV-2 viral load was a risk factor, but CCL5 was a protective factor for ICU admission or mortality during hospitalization
Guo et al[30], China	Prospective cohort	195 (16/132/41/6) (M/I/S/C)	33.74/33.59/32.10/27.53 (M/I/S/C)	Yes	The higher initial viral load was associated with disease severity in COVID-19 patients
Tanner et al[31], United Kingdom	Prospective cohort	185 (IP)	N/A	Yes	The SARS-CoV-2 Ct value at admission was independently related with mortality
Berastegui-Cabrera et al[32], Spain	Prospective cohort	72 (9 OP/63 IP)	N/A	No	The viral load in the upper respiratory airways was associated with poor outcome
Karahasan Yagci et al[33], Turkey	Retrospective study	730 (446 OP/284 IP)	(27.8/29.4/27.9) (M/I/S)	No	The viral load was not a significant risk factor for hospitalization or fatality
Le Borgne et al[34], France	Retrospective study	287 (42 NS/245 SV)	4.99 vs 4.76 (NS vs SV)	No	The viral load in the first nasopharyngeal swab was neither a predictor of severity nor of death in SARS-CoV-2 infection
Hasanoglu et al[35], Turkey	Prospective cohort	60 (15 AS/45 SM)	N/A	No	Asymptomatic individuals' viral loads were found to be substantially greater than symptomatic patients'
Bakir et al[36], Turkey	Retrospective study	158 (45 OP/113 IP)	26.76 vs 27.53 (OP vs IP)	No	The quantity of SARS-CoV-2 viral load did not correlate with the severity of the pulmonary lesions shown on chest CT
Ng et al[37], USA	Retrospective study	133	N/A	No	The viral loads in more seriously ill hospitalized patients were not significantly different from those in outpatient clinics

AS: Asymptomatic; C: Critical; CCL5: Chemokine (C-C motif) ligand 5; Cq: Cycle quantification; Ct: Cycle threshold; CT: Computerized tomography; FT: Fatality; I: Intermediate; IP: Inpatient; M: Mild; N/A: Not applicable; NP: Nasopharyngeal; NS: Non-survivor; OP: Outpatient; RT-PCR: Reverse transcription polymerase chain reaction; S: Severe; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; SM: Symptomatic; SV: Survivor.