Background Understanding the dynamics of SARS-CoV-2 household transmission is important for adequate infection control measures in this ongoing pandemic. Methods Households were enrolled upon a PCR-confirmed index case between October and December 2020, prior to the COVID-19 vaccination program. Saliva samples were obtained by self-sampling at day 1, 3, 5, 7, 10, 14, 21, 28, 35, and 42 from study inclusion. Nasopharyngeal swabs (NPS) and oropharyngeal swabs (OPS) were collected by the research team at day 7 and capillary blood samples at day 42. Household secondary attack rate (SAR) and per-person SAR were calculated based on at least one positive saliva, NPS, OPS, or serum sample. Whole genome sequencing was performed to investigate the possibility of multiple independent SARS-CoV-2 introductions within a household. Results Eighty-five households were included consisting of 326 (unvaccinated) individuals. Comparable numbers of secondary cases were identified by saliva (133/241; 55.2%) and serum (127/213; 59.6%). The household SAR was 88.2%. The per-person SAR was 64.3%. The majority of the secondary cases tested positive in saliva at day 1 (103/150; 68.7%). Transmission from index case to household member was not affected by age or the nature of their relationship. Phylogenetic analyses suggested a single introduction for the investigated households. Conclusion Households have a pivotal role in SARS-CoV-2 transmission. By repeated saliva self-sampling combined with NPS, OPS, and serology, we found the highest SARS-CoV-2 household transmission rates reported to date. Salivary (self-)sampling of adults and children is suitable and attractive for near real-time monitoring of SARS-CoV-2 transmission in this setting.

Background We assessed the association between SARS-CoV-2 viral load and hospital-, ICU admission and in-hospital mortality. Methods All SARS-CoV-2 positive persons with a combined nasopharyngeal (NP) and oropharyngeal (OP) swab that was collected between March 17, 2020, and March 31, 2021, in Public Health testing facilities were included. Results From 20.207 SARS-CoV-2 positive persons, 310 (1.5%) were hospitalized within 30 days. High viral loads (Cp < 25) were associated with an increased risk of hospitalization as compared to low viral loads (Cp > 30), ORadjusted [95%CI]: 1.57 [1.11-2.26], adjusted for age and sex. The same association was seen for ICU admission, ORadjusted [95%CI]: 7.06 [2.15-43.57]. The median [IQR] Cp-value of the 17 patients who deceased in-hospital was significantly lower compared to the 226 survivors: 22.7 [3.4] vs. 25.0 [5.2]. Discussion Higher initial SARS-CoV-2 viral load is associated with an increased risk of hospital admission, ICU admission, and in-hospital mortality. Our findings emphasize the added value of reporting SARS-CoV-2 viral load or Ct/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 or early initiation of antiviral therapy.

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.

Background: We assessed the SARS-CoV-2 reinfection rate in a large patient cohort, and evaluated the effect of varying time intervals between two positive tests on assumed reinfection rates using viral load data. Methods: All positive SARS-CoV-2 samples collected between 1 March 2020 and 1 August 2021 from a laboratory in the region Kennemerland, the Netherlands, were included. The reinfection rate was analyzed using different time intervals between two positive tests varying between 2 and 16 weeks. SARS-CoV-2 PCR crossing point (Cp) values were used to estimate viral loads. Results: In total, 679.513 samples were analyzed, of which 53.366 tests (7.9%) were SARS-CoV-2 positive. The number of reinfections varied between 260 (0.52%) for an interval of 2 weeks, 89 (0.19%) for 4 weeks, 52 (0.11%) for 8 weeks, and 37 (0.09%) for a minimum interval of 16 weeks between positive tests. The median Cp-value (IQR) in the second positive samples decreased when a longer interval was chosen, but stabilized from week 8 onwards. Conclusions: Although the calculated reinfection prevalence was relatively low (0.11% for the 8-week time interval), choosing a different minimum interval between two positive tests resulted in major differences in reinfection rates. As reinfection Cp-values stabilized after 8 weeks, we hypothesize this interval to best reflect novel infection rather than persistent shedding.

Background: Oropharyngeal (OP) and nasopharyngeal (NP) sampling has historically been considered the reference specimen type used for respiratory virus detection. Saliva could be a less invasive alternative for SARS-CoV-2 detection, but limited evidence is available. Methods: The technical and clinical performance of saliva was compared to OP/NP on the Hologic Panther platform with two Aptima assays, the End-Point Transcription-Mediated Amplification assay (EP-TMA) and Real-Time Transcription-Mediated Amplification assay (RT-TMA). The samples were collected at the Public Health Service Testing Site XL location in Schiphol Amsterdam Airport. At the site, the Regional Public Health Laboratory Kennemerland (RPHLK) has a fully equipped laboratory facility. Results: A total of 374 samples (187 OP/NP swabs and 187 saliva samples) were collected from 187 unique patients. The Real-Time Transcription-Mediated Amplification assay (RT-TMA) resulted in comparable sensitivities for the detection of SARS-CoV-2 in both the OP/NP swabs (88.3%; 113/128) and saliva samples (87.5%; 112/128). The End-Point Transcription-Mediated Amplification assay (EP-TMA) analyses showed a similar sensitivity (86.7%; 111/128) in the OP/NP swabs but a lower sensitivity in the saliva samples (80.5%; 103/128). Within the discordant analyses, we found no associations in the symptoms, earlier SARS-CoV-2 infections and eating, smoking, drinking and tooth brushing habits within one hour before testing. Conclusions: The Hologic Panther platform Real-Time Transcription-Mediated Amplification assay (RT-TMA) yields a sensitivity for the detection of SARS-CoV-2 in saliva that is comparable to the OP/NP swabs derived from participants presenting themselves at a public health testing facility with minimal or mild symptoms.