1 Aoki et al.26 Cross-sectional 2021 Japan 24 N/A Female/male RT-PCR There was a high correlation between viral load calculated using the RT-PCR cycle threshold value and antigen concentration. The tendency to decrease antigen concentration over time after disease onset is associated with viral load. Ct value: 25 N/A N/A N/A N/A N/A SQT is fully compatible with RT-PCR and should be useful in diagnosing COVID-19 in any clinical setting Nasopharyngeal swab 2 Aydin et al.27 Case series 2021 Turkey 125 62,1 48.8% male RT-PCR The effect of SARS-CoV-2 viral load on saliva and other substances was not found in their prognosis. Ct value: 22.28 N/A Hypertension, COPD, DM, malignancy, immune deficiency, cardiovascular disease, and asthma N/A N/A N/A The viral load of saliva in the early stages of COVID-19 infection may have a high prognostic value in predicting disease progression in patients over 45 years of age. Saliva is a good substance in COVID-19 screening Oronasopharyngeal (ONP) samples and saliva samples 3 Berastegui-Cabrera et al.28 Cross-sectional 2021 Spain 72 66 56% male RT-PCR No association was found between viral load in NP samples and the presence of SARS-CoV-2 RNAemia. The absence of differences in NP viral load between patients with SARS-CoV-2 RNAemia and without it proves that the clinical development index of COVID-19 patients is better than that of NP viral load. The median viral load in NP swabs = 6.98 log10 copies/ml (IQR, 5.15–8.20) Arthromyalgias, coryza, cough, dyspnea, headache, odynophagia, diarrhea, anosmia, weakness, and dysgeusia Chronic kidney disease, solid-organ transplantation, connective tissue disease, and chronic liver disease Leukocytes: 5.22, 7.00, Neutrophils: 3.49, 4.79, Lymphocytes: 0.58, 1.36, Platelets: 158, 248, Hemoglobin: 13, 13.8, AST: 37, 26, ALT: 33, 23, Bilirubin: 0.59, 0.46, Sodium: 2, 4, Potassium: 2,1, Creatinine: 4, 6, C-reactive protein: 97.9, 44.9, Ferritin: 625.6, 442, D-dimers: 1430, 620, LDH: 450, 251.5, ARDS, multiple organ failure, IMV, ICU admission, mortality N/A The presence of RNAemia SARS-CoV-2, in the first emergency assessment, is more common in patients with severe chronic underlying disease, such as chronic liver disease and solid organ transplantation, with viral load in the upper respiratory tract and with adverse outcomes Nasopharyngeal swabs 4 Buetti et al.29 Cross-sectional 2021 Switzerland 90 62.5 78.9% male RT-PCR Nasopharyngeal swab Viral load (log10 copies/ml), median [IQR]: 3.3 [1.8; 5.2] That viral load in the LRT was associated with the 6-week mortality Cardiovascular, Immunosuppression, DM, Renal failure, Cancer, and Chronic respiratory failure N/A N/A N/A Delay in LRT virus averaged approximately 30 days in critically ill patients, and viral load in LRT was associated with 6-week mortality 5 Buder et al.30 Cohort 2021 Germany 59 Median: 48 years 49% Quantitative real-time PCR of respiratory samples Median viral load (IQR): 6.80 × 104 (4.75 × 103–1.81 × 106) RNA copies/ml N/A 10 patients had immunosuppression N/A 34 outpatient, 20 admitted to ICU Higher viral load correlated with a higher chance of viral transmission SARS-CoV-2 infectivity correlated with viral load, with the best predictor of infectivity being viral loads above 1.0 × 107 RNA copies/ml. The probability of virus isolation from respiratory samples also correlated positively with viral load. Seroconversion terminated SARS-CoV-2 infectivity 6 Cho et al.31 Pospective observational 2020 China 75 36.4 ± 16.3 48% male RT-PCR Nasopharyngeal and deep throat swabs There was no correlation between the recovery time of olfactory or gustatory disorders and the Ct value of PCR was sampled indirectly from nasopharyngeal swabs and deep throat reflected the viral load of SARS-CoV-2. Ct value: 28.3 ± 6.7 Rhinorrhea, Purulent nasal discharge, Taste change, Nasal blockage, Epistaxis, Cough, Fever, Dyspnea, and smell change. N/A N/A N/A N/A There is no association between severity and improvement of olfactory and taste disorders with SARS-CoV-2 viral load 7 Chua et al.32 Cross-sectional 2021 China 91 Asymptomatic Male:8.6 (4.3–11.0), Symptomatic Mean (IQR): 9.2 (4.0–15.0) Asymptomatic 57.1% male, Symptomatic 44.4% male RT-PCR Nasopharyngeal swab (NPS), and saliva samples collected on admission The onset days of symptoms for all patients were inversely related to the NPS and saliva viral loads. Viral load (log10 copies/ml): lymphopenia (NPS, Saliva): 6.7, 5.8 viral load (log10 copies/ml):: nonlymphopenia (NPS, Saliva): 6.2, 4.9 N/A Total white cell count (×109/L): 6, 5.8-Hemoglobin (g/dl): 12.8, 13.2-Platelets (×109/L): 258.4, 278.1-Urea (mmol/L): 3.4, 3.9-Creatinine (µmol/L): 41.6, 44.9-Creatine Kinase (U/L):122.5, 99.7-Troponin I (ng/l): 1.9, 11.3-C Reactive Protein (mg/dl): 1.4, 1.7-Erythrocyte Sedimentation Rate (mm/h):8.6, 12- N/A N/A Salivary viral loads in hospitalized children with clinical and immune profiles are better than NPS 8 de la Calle et al.33 Cross-sectional 2021 Spain 455 64.9 ± 18.1 56% male rRT-PCR nasopharyngeal Patients with respiratory failure had a higher viral load at admission than those who did not. Low viral load (Ct > 30), Intermediate viral load (Ct 25–30): 1.81, high viral load (Ct < 25): 2.99 Fever, Vomiting, Cough, Tachypnea, Diarrhea, SpO2 < 90% air room, Myalgia and Dyspnea Cardiovascular disease, chronic renal disease, chronic lung disease, DM, immunosuppression, obesity, current or former smoker, and chronic liver disease LDH (U/L): 326.6, GOT (U/L): 32, GPT (U/L): 25, CPK (U/L): 86, TnT (U/L): 10.5, C-reactive protein (mg/dl): 7.7, Ferritin (mg/dl): 699, D-dimers (ng/ml): 664 Need for supplemental oxygen, ARDS, noninvasive mechanical ventilation, ICU admission, Septic shock, Prone position, MACE event, Acute kidney injury (AKI), Venous thrombosis, Hepatitis, Respiratory failure, Invasive mechanical ventilation, and mortality N/A The SARS-CoV-2 viral load, measured by Ct value of rRT-PCR in pharyngeal swabs at admission, is a good indicator of the prognosis for respiratory failure 9 He et al.34 Cohort 2020 China 23 41 43.5% males qRT-PCR Pharyngeal swab Minimum viral load: 40 Ct. Asymptomatic type patients had lower viral loads than common and severe types Fever, cough, nasal congestion, dizziness, fatigue, arthralgia, human endogenous retrovirus-H (Hervs) and Human picobirnavirus (HPBV) Patients with severe disease had more abnormal laboratory test results (including leukopenia and lymphocytopenia) no significant correlation was observed between age and Ct value also no association between Ct value and severity of illness was observed. Significant positive relation has been detected between peak viral load and severity of illness. Weaker transmission capacity of asymptomatic cases due to the lower viral load Asymptomatic type patients had lower viral loads than common and severe types 10 Jacot et al.35 Cross-sectional 2020 Switzerland N/A 0-99 years Female/male RT-PCR Nasopharyngeal swab Range: 3–10 log copies/ml. Median: 6.78 log10 copies/ml In the first period of covid-19 outbreak viral load was higher SARS-CoV-2 viral load seem to be a substandard predictor of disease outcome, COVID-19 disease severity is not significantly related to viral replication in the upper and lower respiratory tracts Fever cough N/A N/A In the first period of covid-19 outbreak viral load was higher below 1000 copies/ml values can be considered at slight risk of transmission Despite there are significant differences between viral loads of different viruses, SARS-Cov-2 had a alike viral load to Respiratory syncytial virus and influenza B than other coronaviruses 11 Jain et al.36 Comparative 2021 India 200 group A 35.23 ± 11.99, group B 35.32 ± 12.92 60% male RT-PCR Nasopharyngeal swab Group A with olfactory and taste dysfunction: 24.43 Ct. Group B without OTD: 27.39 Ct. The patients with taste and olfactoryimpairment at diagnosis had more viral load than patients without taste and olfactoryimpairment Loss of smell and taste malaise sore throat cough fever nasal discharge N/A RT-PCR was utilized to test The COVID-19, with 3 gene detection: RdRp (RNA-dependent RNA polymerase), E (Envelope encoding) gene, and N (Nucleocapsid encoding) gene. For analysis cycle threshold was utilized. N/A N/A The patients with OTD at diagnosis had more viral load than patients without OTD 12 Kam et al.37 Cohort 2021 Singapore 17 7.7 Female/male RT-PCR Nasopharyngeal swab Symptomatic: 28.6 Ct. Asymptomatic: 36.7 Ct higher viral loads was seen in symptomatic children in comparison to asymptomatic children Upper respiratory tract symptoms with mild sickness signs N/A N/A patients with mild and severe chest CT involvement had significantly lower viral load in comparison to patients with no chest CT lesions. symptomatic children in had high viral load in the first stage of sickness indicates the transmission potential of presymptomatic children. Children with symptomshad higher viral loads than children without symptoms 13 Karahasan Yagci et al.38 Cohort 2020 turkey 730 35 49.9% female RT-qPCR Nasopharyngeal swab Without CT scan involvement: 24.9 mild CT involvement: 27.8 moderate CT involvement: 29.4 severe CT involvement: 27.9. The oppositecorrelation of chest CT Total severity score (TSS) and viral load was seen. Significantly higher viral loads was observed in patients with no chest CT lesions in comparison to patients with mild and severe chest CT involvement Fever, cough and dyspnea Hypertension, diabetes mellitus, cardiovascular disease, chronic obstructive pulmonary diseases (COPD), cancers, HIV, collagenosis, and chronic liver disease N/A 284 (39%) patients were admitted to hospital and 27 of patientsexpired during the hospitalization. N/A The oppositecorrelation of chest CT total severity score (TSS) and viral load 14 Kawasuji et al.39 Case-control 2020 Japan 28 Median age: 45.5 years 53.6% male rRT-PCR Nasopharyngeal swab 33.6 ± 5.5 Ct. A significant viral load and recovery time differencewas observed between patients with pulmonary involvement and patients without pulmonary involvement N/A N/A N/A Significantly higher viral load at the beginning of sampling in symptomatic patients than in asymptomatic patients was observed. Also, Children had significantly higher viral load than adults in the beginning of sampling. A high nasopharyngeal viral load can be connected to the secondary transmission of COVID-19 Secondary transmission of COVID-19 can be related to high nasopharyngeal viral load. Additionally, the viral load can help describe why transmission is observed in some patients, but not in others, particularly among patients who live in same house 15 Kim et al.40 Retrospective 2021 South Korea 106 Mean age: 28.0 ± 9.3 years 43.4% male RT-PCR Nasopharyngeal/oropharyngeal swab 33.6 ± 5.5 Ct. Viral load and recovery time were significantly different between pulmonary involvement patients and patients without pulmonary involvement was observed Cough, fever, headache, hyposmia, rhinorrhea, sputum, muscle pain, diarrhea, chest pain, ocular pain Rhinitis, asthma, migraine, iron deficiency, anemia, hyperlipidemia, endometriosis, depression disorder, hair loss, atopic dermatitis N/A Recovery times were significantly slower in the patients with pulmonary involvement than patients without involvement. N/A Viral load and recovery time were significantly different between pulmonary involvement patients and patients without pulmonary involvement was observed. The cycle threshold cutoff value for the existence of pneumonia was 31.38 16 Kociolek et al.41 Retrospective 2020 USA 817 0-17 years 52.1% male RT-PCR Nasopharyngeal swab Asymptomatic children: 2.0 × 103 copies/ml symptomatic children: 1.3 × 107 copies/ml. In children without symptoms lower viral load was found in their nasopharynx/oropharynx than children with symptoms Cough, fever/chills, dyspnea, pharyngitis, loss of taste or smell, headache, abdominal pain, diarrhea, fatigue, myalgias, congestion/rhinorrhea, nausea/vomiting, rash, or conjunctivitis Immunocompromised = 51. Diabetes = 19 N/A Ct values were significantly higher in children without symptoms than children with symptoms. Also, significantly lower viral loads was observed in asymptomatic than symptomatic children. N/A Asymptomatic children had low viral loads in their nasopharynx/oropharynx than children with symptoms 17 Kriegova et al.42 Prospective 2021 Czech Republic 1038 50.0 ± 3.3 Female/male RT-PCR Nasopharyngeal swab Asymptomatic and mild group 23.65 (±7.62) Ct. Moderate group 27.68 (±6.98) Ct. Severe and critical group 26.52 (±4.82) Ct. High levels of virus in the respiratory tract and excessive producing of chemokines and cytokines between first 2 weeks from the onset of symptoms were significantly related to severity of the COVID-19 N/A N/A N/A self-conductnasal-swab in combination with direct RT-qPCRare easy, low-cost and quick CoV-2 testing method which could significantly increase the extent of the teststrategies which are needed to control the expansion of COV-19 during and post-pandemic era N/A High levels of virus in the respiratory tract and too much productionof chemokines and cytokines and between the first two weeks from the onset of symptoms were significantly related to severity of the COVID-19 18 Kwon et al.43 Prospective 2020 South Korea 31 32-72 years 58% female Nasopharyngeal swab RT-PCR Initial viral load at five toten days from onset of symptoms in the asymptomatic and mild group, moderate group, and the severe and critical group was 32.65 (±7.62), 27.68 (±6.98), and 26.52 (±4.82) cycles Fever, chill, cough, sputum, sore throat, dyspnea, rhinorrhea chest pain, headache, myalgia, nasal congestion, hyposmia, hypogeusia, pneumonia Diabetes mellitus, hypertension, chronic lung disease, chronic liver disease, obesity (body mass index > 25), smoking Old age, initial low WBC count, low platelet count, high CRP level, and fever were identified as factors associated with severity Early increases in type I IFN response might be involved in the pathophysiology of severe COVID-19 by eliciting subsequent excessive responses of multiple cytokines and chemokines N/A Higher viral load, stronger antibody response, and excessive inflammation at first two weeks from onset of symptoms are related to the COVID-19 severity 19 Le Borgne et al.44 Retrospective 2021 France 287 50.0 to 73.0, median age: 63.1 65.8% male Pharyngeal swabs qRT-PCR 4.76 (3.29–6.06) log10 copies/reaction Nasopharyngeal viral load measured by RT-PCR during beginning emergency department (ED) viral load is not predictor of severity and mortality in COVID-19 patients N/A Hypertension, cardiovascular disease, diabetes mellitus, renal insufficiency, dialysis, COPD, malignancies, immunotherapy, corticosteroids At emergency department admission, patients who didn't survive in comparison to survived patients. had significantly higher C-reactive protein (122 vs. 74 mg/L, p = .007) and creatinine (p = .036). Nonsurvivors were also more likely to present with anemia (p = .003) and lymphopenia (p = .02) than survivors Forty-two patients (14.6%) died. Nasopharyngeal viral load was measured by RT-PCR at emergency department admission viral load isn't predictor of severity and mortality in COVID-19 patients 20 Piubelli et al.45 Cross-sectional 2021 Italy 273 N/A Female/male RT-PCR Nasal and Pharyngeal swabs Viral load decreased during 2 months of quarantine (Ct decreased from 24 to 34). Alongside, the number of patients who need intensive care significantly decreased because of the reduction of viral load N/A N/A More probable in high-transmission setting compared with low-transmission setting ICU admission (5.3%) N/A N/A 21 Rauch et al.46 Cohort 2021 USA 1808 27.3 ± 11 53% male RT-qPCR and CRISPR-based assay Nasopharyngeal swab Viral load = 286–510,000 copies/μl. The shift of viral load is shown in those who stayed at home Nasal congestion, sore throat, fatigue, anosmia N/A 8 positive participants by CRISPR-based assay and 9 by RT-qPCR were detected All were alive at the end of the study N/A The prevalence of SARS-CoV-2 in cohort 2 was changed and it was because of decreased community restrictions and increased social interactions 22 Sarkar et al.47 Cross-sectional 2020 India 138 N/A Female/male RT-PCR Nasopharynx swab (NPS) and oropharynx swab (OPS) In those with Ct values between 17 and 23, patients had severe infections N/A N/A N/A N/A In high viral load cases, the rate of transmission was 8-times more than low viral load cases. Patients with Ct above 33-34 were not contagious In individuals with high viral load, the possibility of transmission was almost 8 times higher compared to low viral load individuals. Of those who were infected, 7% had a high viral load, 9% moderate viral load, and 84% low viral load based on Ct values. The probability of transmission in those with high viral load was 6.25 in comparison with law viral load with 0.8 23 Shlomai et al.48 Cross-sectional descriptive 2020 Israel 170 62 58% Male Nasopharyngeal samples RT-PCR Viral load was significantly higherin ventilated and nonsurvivors patients (eightfold more than other patients). Low viral load was associated with decreased risk of mortality and intensive care Hypoxemia N/A N/A 21 death N/A Viral load was directly linked to hypoxemia. Viral load was significantly related toblood oxygen saturation. The patient's age significantly correlated with viral load 24 Shrestha et al.49 Cohort 2020 USA 230 health care personnel (HCP) N/A Male 36% PCR Nasopharyngeal swab Viral load in 2 or 3 days after onset of symptoms was the peak. Time since onset of symptoms was significantly related to viral load N/A Chronic lung disease, current smoker, chronic heart disease, hypertension, liver cirrhosis, immunocompromised, diabetes mellitus, chronic kidney disease N/A N/A N/A 86.5% of transmission potential was in the first 5 days since onset of symptoms 25 Singanayagam et al.50 Cross-sectional 2020 England 754 samples from 425 symptomatic cases 0-100 years old Female/male RT-PCR Nose, throat, combined nose-and-throat and nasopharyngeal swabs There was no difference in Ct value between asymptomatic (Ct = 31.23), mild to moderate (Ct = 30.94), and severe cases (Ct = 32.55). In the first week of onset of symptoms, viral load was higher than the second week N/A N/A In 42% of cases, culture was positive. The culture positivity during the first week of infection was significantly higher than the second week N/A N/A Cases in the 81–100 year age group were more asymptomatic than other groups 26 Soria et al.51 Cohort 2020 Spain 448 71.04 ± 18.29 45.7% male RT-PCR Nasopharyngeal swabs Mean Ct: mild (35.75 ± 0.45), moderate (32.69 ± 0.37), severe (29.58 ± 0.70). Viral load is a predictor of disease severity. High virus loading worsens the prognosis of the disease. Ct value was significantly law in the severe group in comparison with the moderate and mild group N/A Hypertension, cardiovascular disease, diabetes. Obesity, asthma, COPD N/A Cases of the severe group include 23% of total cases and all of them were admitted. Also, 18.3% died during 90 days after diagnosis, 75 cases in the severe group, three cases in moderate, and four in the mild group N/A N/A 27 To et al.52 Cohort 2020 China 23 62 56.5% male RT-qPCR Oropharyngeal saliva samples The median viral load was 5 × 2 log10 copies/ml. The first week after the onset of symptoms, the viral load is high but decreases over time Fever (96%), cough (22%), chills (17%), dyspnea (17%), runny and blocked nose, sore throat, chest discomfort, nausea, diarrhea, myalgia, malaise. In 15 (65%) CXR abnormalities were seen. In 17 (74%) multifocal ground-glass lung opacities were seen 48% had clinical medical illnesses including hypertension and diabetes Those patients who had comorbidities had a lower anti-RBD IgG OD compared to those without comorbidities Five patients were admitted to ICU, two of them required intubation, and also two of them died N/A Older age was associated with a higher viral load. The antibody response occurred 10 days or later since the onset of symptoms 28 To et al.53 Cross-sectional 2020 China 12 62.5 58% male RT-qPCR Nasopharyngeal or sputum specimen The median viral load was 3.3 × 106 copies/ml. On the first day of hospitalization viral load was slightly higher than other days. After day 11 viral load started to shed till being undetectable N/A N/A According to viral culture, saliva contains live viruses and potentially can transmit the virus At the end of the survey, all patients were alive N/A Saliva can be obtained from the patient without invasive procedure and it leads to reduce in nosocomial transmission of the virus 29 Trunfio et al.54 Retrospective cross-sectional 2021 Italy 200 56 58% male RT-PCR Nasopharyngeal swab Viral load was associated with the severity of the disease Gastrointestinal, neurological, respiratory, and systemic involvement, headache, olfactory and gustatory dysfunction, nausea and vomiting, diarrhea, fever, arthralgia, asthenia and malaise, cough, dyspnea, pharyngitis, and runny nose Participants of group A (Ct ≤ 20) had at least one comorbidity that was significantly different from the other two groups. Hypertension, COPD, asthma, obesity, active smoking, diabetes, cancer N/A