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.

Antibody response to SARS-CoV-2 infection in humans: a systematic review

“…A number of studies reported seroconversion for total antibody (combined IgG, IgM and/or IgA), [15][16][17][18][19][20][21] however the focus of findings presented is for specific antibody isotypes. For IgG, mean or median time to seroconversion ranged from 12 -15 days post symptom onset, 7,9,15,[22][23][24][25][26] with wide variation in first to last detection of IgG from 4 -73 days post symptom onset although reporting methods varied by study. 15,[27][28][29][30][31][32][33] For IgM, mean or median time to seroconversion ranged from 4-14 days post symptom onset, 7,9,15,[22][23][24]26,31,34 again with variations in reporting methods, study quality, and sample size giving rise to uncertainty around findings.…”

“…Across the included studies, the majority of subjects developed detectable neutralising antibodies in response to SARS-CoV-2 infection in both human 7,18,22,29, and animal 41,[89][90][91][92] participants.…”

“…were found in all individuals tested, suggesting specific neutralising antibodies are produced following infection despite low overall plasma neutralising ability. 87 Neutralising antibodies were generally detectable between 7 -15 days following disease onset, 7,18,75,84,85,88,93,94 increasing over days 14 -22 before plateauing 22,68,69,88,93,94 and declining over a period of six weeks. 69,85,88,95 Evidence from one medium-quality pre-print study suggests neutralising antibody titres reduced significantly among 27 convalescent patients around six weeks following disease onset to a mean neutralisation half maximum inhibitory dilution (ID50) of 596.…”

“…• Most studies report no relationship between time to seroconversion for IgG or IgM and disease severity. 22,35,53,56 • A number of studies report earlier antibody response to more severe disease 134,135 , including specifically for IgG; 7 a shorter time to peak antibody titre, 19,26,[136][137][138] including specifically for IgA; 30 and that IgG persists for longer in severe disease compared to milder cases. 139,140 • Three studies report an earlier antibody response to milder disease, 19,43 including specifically IgM 141 and IgA, 140 shorter time to peak for IgG, 140 and IgG persists for longer compared to severe cases.…”

Evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for IgG antibody detection in severe and mild COVID-19 cases using a Luminex bead-based assay

“…Since December 2019, Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has spread at an unprecedented speed and scale, resulting in 500,000 deaths, 11,500,000 diagnosed cases (as of 10/7/2020) 1 and likely many more undiagnosed cases with mild or no symptoms (10 fold) 2 . Nucleic acid (PCR) tests are widely used for clinical diagnosis and provide good estimates on the duration of viral shedding [3][4][5] . However, it remains uncertain how many people develop protective antibodies after recovery and for how long [6][7][8] .…”