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OBJECTIVEUsing data from European prospective household studies, we systematically compared the symptom burden of the wild-type and Alpha variant infected individuals versus the Omicron BA.1 and BA.2 infected individuals across paediatric and adult age-groups. In addition, we measured the impact of COVID-19 vaccination on the Omicron symptom burden. METHODSThe household transmission studies were conducted during the wild-type and Alpha period (April 2020 to April 2021) and the early Omicron BA.1 and BA.2 dominant period (January to March 2022). All three studies used similar protocols. Households were prospectively followed from detection of the first SARS-CoV-2 index case until at least day 21 including (repeated) PCR testing, paired serology and daily symptom reporting for all household members. To avoid possible index-case ascertainment bias, we restricted analyses to secondary household cases. Age-stratified SARS-CoV-2 symptom burden was compared for wild-type/Alpha versus Omicron infections and for primary versus primary plus booster series vaccinated adult cases. FINDINGSIn total 216 secondary cases from wild-type/Alpha, and 130 from the Omicron period were included. Unvaccinated children <12 years experienced more symptoms and higher maximum and cumulative severity scores during the Omicron compared to the wild-type/Alpha period (p=0.004, p=0.011 and p=0.075, respectively). In adults, disease duration and maximum and cumulative severity scores were reduced during the Omicron period. Adjusted for age, gender and prior immunity Omicron was associated with lower odds for loss of smell or taste (Odds Ratio [OR]: 0.14; 95%CI 0.03-0.50), and higher, but non-significant odds for upper respiratory symptoms, fever and fatigue (ORs varying between 1.85-2.23). Comparing primary versus primary plus booster vaccinated adult cases during the Omicron period no differences were observed in disease severity or duration (p[≥]0.12). INTERPRETATIONIn children, the Omicron variant causes higher symptom burden compared to the wild-type/Alpha. Adults experienced a lower symptom burden possibly due to prior vaccination. A shift in most frequently reported symptoms occurred with a marked reduction in loss of smell or taste during the Omicron period. An additional effect of booster vaccination on symptom severity in infected adults compared to primary series only, could not be demonstrated.
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BackgroundWe aimed to assess the association between initial SARS-CoV-2 viral load and the subsequent hospital and intensive care unit (ICU) admission and overall survival. MethodsAll persons with a positive SARS-CoV-2 RT-PCR result from a combined nasopharyngeal (NP) and oropharyngeal (OP) swab (first samples from unique persons only) that was collected between March 17, 2020, and March 31, 2021, in Public Health testing facilities in the region Kennemerland, province of North Holland, the Netherlands were included. Data on hospital (and ICU) admission were collected from the two large teaching hospitals in the region Kennemerland. ResultsIn total, 20,207 SARS-CoV-2 positive persons were included in this study, of whom 310 (1.5%) were hospitalized in a regional hospital within 30 days of their positive SARS-CoV-2 RT-PCR test. When persons were categorized in three SARS-CoV-2 viral load groups, the high viral load group (Cp < 25) was associated with an increased risk of hospitalization as compared to the low viral load group (Cp > 30) (ORadjusted [95%CI]: 1.57 [1.11-2.26], p-value=0.012), adjusted for age and sex. The same association was seen for ICU admission (ORadjusted [95%CI]: 7.06 [2.15-43.57], p-value=0.007). For a subset of 243 of the 310 hospitalized patients, the association of initial SARS-CoV-2 Cp-value with in-hospital mortality was analyzed. The initial SARS-CoV-2 Cp-value of the 17 patients who deceased in the hospital was significantly lower (indicating a higher viral load) compared to the 226 survivors: median Cp-value [IQR]: 22.7 [3.4] vs. 25.0 [5.2], OR[95%CI]: 0.81 [0.68-0.94], p-value = 0.010. ConclusionsOur data show that higher initial SARS-CoV-2 viral load is associated with an increased risk of hospital admission, ICU admission, and in-hospital mortality. We believe that our findings emphasize the added value of reporting SARS-CoV-2 viral load based on Cp-values to identify persons who are at the highest risk of adverse outcomes such as hospital or ICU admission and who therefore may benefit from more intensive monitoring.
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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{middle dot}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 ({beta}: -0{middle dot}03, 95CI% -0{middle dot}03 to -0{middle dot}02, p<0{middle dot}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{middle dot}1% vs. 17{middle dot}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.
