SARS-CoV-2 viral load distribution reveals that viral loads increase with age: a retrospective cross-sectional cohort study

Abstract

ObjectiveTo describe the SARS-CoV-2 viral load distribution in different patient groups and age categories.MethodsAll SARS-CoV-2 RT-PCR results from nasopharyngeal (NP) and oropharyngeal (OP) swabs (first PCR from unique patients only) that were collected between January 1 and December 1, 2020, predominantly in the Public Health Services regions Kennemerland and Hollands Noorden, province of North Holland, the Netherlands were included in this study. Swabs were derived from patients with respiratory symptoms who were presented at the general practitioner (GP), hospital, or hospital health care workers (HCWs) of four regional hospitals, nursing home residents and HCWs of multiple nursing homes, and in majority (>75%) from Public Health testing facilities of the two Public Health Services. SARS-CoV-2 PCR crossing point (Cp) values were used to estimate viral loads (higher Cp-values indicate lower viral loads).ResultsIn total, 278.455 unique patients were tested of whom 9·1% (n=25.374) were SARS-CoV-2 positive. As there were differences in viral load distribution between tested populations, further analyses focused on PCRs performed by public health services (n=211.914) where sampling and inclusion were uniform. These data reveal a clear relation between age and SARS-CoV-2 viral load, with especially children aged<12 years showing lower viral loads than shown in adults (β: −0·03, 95CI% −0·03 to −0·02, p<0·001), independent of sex and/or symptom duration. Interestingly, the median Cp-values between the oldest (>79 years) and youngest (<12 years) population differed by over 4 PCR cycles, suggesting approximately a 16-fold difference in viral load. In addition, the proportion of children aged <12 years with a low load (Cp-value >30) was significantly higher compared to the other patients (31·1% vs. 17·2%, p-value<0.001).ConclusionWe observed that in patients tested by Public Health Services, SARS-CoV2 viral load increases significantly with age. Previous studies suggest that young children (<12 years) play a limited role in SARS-CoV-2 transmission. Currently, the relation between viral load and infectivity is not yet well understood, and further studies should elucidate whether the lower viral load in children is indeed related to their suggested limited role in SARS-CoV-2 transmission. Moreover, as rapid antigen tests are less sensitive than PCR, these results suggest that SARS-CoV-2 antigen tests could have lower sensitivity in children than in adults.

Viral Load Difference between Symptomatic and Asymptomatic COVID-19 Patients: Systematic Review and Meta-Analysis

“…The high heterogeneity observed was influenced by age and gender, as evidenced by the meta-regression. These findings are in accordance with some previous analyses demonstrating that the viral load increases with age [ 21 ] and is higher in females [ 22 ]. However, we also cannot use underlying comorbidities, such as arterial hypertension and diabetes, as moderator variables, which have been related to a slower viral shedding [ 23 , 24 ].…”

Diagnostic Accuracy of SARS-CoV-2 Rapid Antigen Detection Testing in Symptomatic and Asymptomatic Children in the Clinical Setting

“…These findings somehow differ from adult data, where sensitivity remained high throughout the first five DPOS (despite being lower at 0 DPOS) ( 6 ), likely here again reflecting the impact of higher VLs in adults on P-RDT sensitivity. Similarly, the trend toward lower sensitivity in children <12 years old is likely explained by lower VLs in younger children, as seen in this study and other publications ( 17 – 19 ). Among symptomatic participants, sensitivity was better in those with COVID-19-typical symptoms, as previously shown in adults ( 6 ), but also in those with >2 symptoms.…”

“…Indeed, although initial studies suggested similar VLs in adults and children, they were limited in sample size and did not take into account DPOS ( 13 – 15 ), which is a major determinant of VL ( 16 ). Recently, studies on larger data sets and/or taking into account DPOS have shown that SARS-CoV-2-infected children have significantly lower VLs than adults ( 17 – 19 ). Another possible explanation for the lower sensitivity could be sampling bias related to the technical challenge of the NPS procedure in children, given that the swab for the P-RDT testing was the second one to be performed.…”

SARS-CoV-2 viral load at presentation to hospital is independently associated with the risk of death

“…These factors include patient age, duration of illness, and antibody sero-status at the point of presentation. [13][14][15] We hypothesised that the association between viral load and clinical outcome seen in early studies may be dependant on other factors rather than independently associated. The aim of the study was therefore to evaluate the association between viral load, as measured by real-time PCR cycle threshold (Ct) value, and outcome whilst carefully adjusting for covariates including age, duration of illness and antibody sero-status.…”