Quantifying antibody kinetics and RNA shedding during early-phase SARS-CoV-2 infection

Abstract

Our ability to understand and mitigate the spread of SARS-CoV-2 depends largely on antibody and viral RNA data that provide information about past exposure and shedding. Five months into the outbreak there is an impressive number of studies reporting antibody kinetics and RNA shedding dynamics, but extensive variation in detection assays, study group demographics, and laboratory protocols has presented a challenge for inferring the true biological patterns. Here, we combine existing data on SARS-CoV-2 IgG, IgM and RNA kinetics using a formal quantitative approach that enables integration of 3,214 data points from 516 individuals, published in 22 studies. This allows us to determine the mean values and distributions of IgG and IgM seroconversion times and titer kinetics, and to characterize how antibody and RNA detection probabilities change during the early phase of infection. We observe extensive variation in antibody response patterns and RNA detection patterns, explained by both individual heterogeneity and protocol differences such as targeted antigen and sample type. These results provide a robust reference for clinical management of individual patients, and a foundation for the mathematical models and serological surveys that underpin public health policies.

Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak

“…Our assays included controls from adults with RT-PCR-confirmed infections, as well as samples from five children with confirmed infections collected at various times post symptom onset, including children from outside the study population (see "Methods-Study participants" for additional details). Neither adult nor child samples <1 week post symptom onset were seropositive by our criteria, consistent with prior reports that infected individuals generally do not become seropositive until at least a week post symptom onset [10][11][12][13][14] . However, all samples ≥1 week post symptom onset were seropositive, and in most cases, the signal greatly exceeded pre-2020 negative controls.…”

“…2a, b). While this convenience sample from children seeking medical care is unlikely to be representative of all children in Seattle, the period seroprevalence measurements for our population are similar to all-age cumulative incidence estimates for the Seattle region based on viral testing and mortality data 20,21 , given the ≈1-2-week lag between symptom onset and seroconversion [10][11][12][13][14] . In addition, the temporal dynamics of seropositivity in our study population mirrors recent viral testing-based findings that infection in Seattle area children was rare before March 2020 22 , but increased markedly in March and April 23 .…”

“…Serological assays, which detect antibodies induced by infection, provide such an approach. When interpreting these assays in a temporal context, note that individuals do not become seropositive until ≈1-2 weeks post symptom onset [10][11][12][13][14] , while PCR-based testing generally only detects viral RNA during the first few weeks after symptom onset 11,12 .…”

Estimating epidemiologic dynamics from cross-sectional viral load distributions

“…We used a least-squares optimization framework to obtain parameter point estimates that gave rise to viral kinetics with the following constraints: the proportion of individuals that are detectable on each day post symptom onset declines in line with existing data (49), and the lower 99 th percentile of possible Ct values is in line with the lowest observed Ct value in our Brigham & Women's Hospital dataset. We used these point estimates to derive informative priors on key model parameters, as described in Table S1.…”

Characterization of cells susceptible to SARS-COV-2 and methods for detection of neutralizing antibody by focus forming assay

“…It has also been noted that following infection with SARS-CoV-2, people typically seroconvert 20 days following symptom onset, and there is increasing evidence suggesting that development of a neutralizing antibody response is a correlate of protection in patients recovered from COVID-19 [19][20][21][22]. The COVID-19 pandemic has highlighted the necessity for testing for neutralizing antibodies.…”