SARS-CoV-2 RNA and antibody dynamics in a Dutch household study with dense sampling frame

This study investigated the dynamics of SARS-CoV-2 infection and diagnostics in 242 household members of different ages and with different symptom severity after SARS-CoV-2 exposure early in the pandemic (March–April 2020). Households with a SARS-CoV-2 confirmed positive case and at least one child in the Netherlands were followed for 6 weeks. Naso (NP)- and oropharyngeal (OP) swabs, oral fluid and feces specimens were analyzed for SARS-CoV-2 RNA and serum for SARS-CoV-2-specific antibodies. The dynamics of the presence of viral RNA and the serological response was modeled to determine the sampling time-frame and sample type with the highest sensitivity to confirm or reject a SARS-CoV-2 diagnosis. In children higher viral loads compared to adults were detected at symptom onset. Early in infection, higher viral loads were detected in NP and OP specimens, while RNA in especially feces were longer detectable. SARS-CoV-2-specific antibodies have 90% probability of detection from 7 days (total Ig) and 18 days (IgG) since symptom onset. For highest probability of detection in SARS-CoV-2 diagnostics early in infection, RT-PCR on NP and OP specimens are more sensitive than on oral fluid and feces. For SARS-CoV-2 diagnostics late after infection, RT-PCR on feces specimens and serology are more valuable.

: ROPE analyses for assessing differences between factors in Figure 5. For Ct-values our ROPE interval is [-1,1] (vertical lines, left panels A1 -G2), which means that we consider differences between Ct-values of less than one as not meaningful. For changes in Ct-value per day (the slope) we choose an interval of [-1/7, 1/7] (vertical line, right panels A2 -G2), which means that we consider differences between Ct-values of less than one per week as not meaningful. When the ROPE is outside the 89% highest posterior density interval (HDI) (blue area), there is a difference.  Average dps until when adults and children have detection probability of at least 99% (A), 90% (C), 50% (E) or 10% (G). Right panels: ROPE analyses for assessing differences between adults and children. Analyses for dps of 99% (B), 90% (D), 50% (F) and 10% (H) detection probability are shown. For Ct-values our ROPE interval is [-1,1] (vertical lines), which means that we consider differences between Ct-values of less than one as not meaningful. When the ROPE is outside the 89% highest posterior density interval (HDI) (blue area), there is a difference.

Figure S4
Figure S4: Differences in Ct between RT-PCR specimens in relation to dps. The black solid line indicates the median difference between the two assays (assay A -assay B) indicated, the shaded region is the 89% Bayesian credible interval. For reference the line y=0 is drawn, where this line crosses the solid line of median difference, the Ct values of the two assays are equal. The dps corresponding to this crossing point is indicated by a blue solid vertical line. The dashed lines indicate where y=0 crosses the top and bottom quantiles of the credible interval. To the left of the leftmost dashed line, we are sure that assay A has a smaller Ct then assay B, and conversely larger to the right of the rightmost line. In between those lines we are not certain, although more area of the credible interval below zero gives more credibility to a smaller Ct for assay A.

Figure S5
Figure S5: ROPE analyses for assessing differences between factors in Figure 5D and S4. Analyses for dps of 90% detection probability (left panels, A-F), 50% probability (middle panels, G-L) and 10% probability (right panels, M-R) are shown. For Ct-values our ROPE interval is [-1,1] (vertical lines), which means that we consider differences between Ct-values of less than one as not meaningful. When the ROPE is outside the 89% highest posterior density interval (HDI) (blue area), there is a difference.    Figure 6A and B. For serology detection probability (in dps) our rope interval is [-2,2], which means that we consider differences between days of less than 2 as not meaningful.

Figure S8
Figure S8: ROPE analyses for assessing differences between factors in Figure 6C and D. For serology detection probability (in dps) our rope interval is [-2,2], which means that we consider differences between days of less than 2 as not meaningful.

Figure S9
Figure S9: Effect of age on the development/magnitude of SARS-CoV-2 specific antibody responses. SARS-CoV-2 specific antibody titers at visit 3 (convalescence phase) in SARS-CoV-2 laboratory confirmed participants. SARS-CoV-2 Spike-specific IgM and IgG (Wantai, left), Spikespecific IgG (microarray S1, middle) and Nucleoprotein-specific IgG (microarray N, right) responses in relation to age (adult and child). On the Y-axis, titers in OD ratio (Wantai) and EC50 values (microarrays) are indicated. The boxplot compactly displays the distribution of a continuous variable. It visualizes five summary statistics (the median, two hinges and two whiskers). The lower and upper hinges correspond to the first and third quartiles (the 25th and 75th percentiles). The upper whisker extends from the hinge to the largest value no further than 1.5 * IQR from the hinge (where IQR is the inter-quartile range, or distance between the first and third quartiles). The lower whisker extends from the hinge to the smallest value at most 1.5 * IQR of the hinge. Differences were analyzed with the Wilcoxon test.

Figure S10
Figure S10: For each of the RT-PCR specimens, these graphs show the probability of detection as a function of days post symptoms. Shaded regions indicate Bayesian credible intervals, dotted lines indicate the 95% prediction interval. Different colors indicate the severity classes. No appreciable difference between the severity classes can be discerned, at reasonable dps values.

Figure S11
Figure S11: For each of serological assays, these graphs show the probability of detection as a function of days post symptoms. Shaded regions indicate Bayesian credible intervals. Different colors indicate the severity classes. No appreciable difference between the severity classes can be discerned.