Virological and Serological Assessment of US Army Trainees Isolated for Coronavirus Disease 2019

Abstract

Background: Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Because viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected.

Methods: Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse-transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2. Cluster and quadratic discriminant analyses of results were performed.

Results: Among 229 recruits isolated for COVID-19, those with a RT-PCR cycle threshold >30.49 (sensitivity 95%, specificity 96%) or having sgRNA log10 RNA copies/mL <3.09 (sensitivity and specificity 96%) at entry into isolation were likely SARS-CoV-2 uninfected. Viral load >4.58 log10 RNA copies/mL or anti-SARS-CoV-2 signal-to-cutoff ratio <1.38 (VL: sensitivity and specificity 93%; anti-SARS-CoV-2: sensitivity 83%, specificity 79%) had comparatively lower sensitivity and specificity when used alone for discrimination of infected from uninfected.

Conclusions: Orthogonal laboratory assays used in combination with RT-PCR may have utility in determining SARS-CoV-2 infection status for decisions regarding isolation.

Keywords: Army recruit; SARS-CoV-2; cycle threshold value; isolation; sgRNA.

Figure 1.

Box plots and summary statistic tables of the distributions of laboratory markers by visit among recruits during coronavirus disease 2019 isolation, October 14–November 23, 2020: (A) cycle threshold (Ct) value, (B) viral load (VL) and subgenomic ribonucleic acid (sgRNA) values (log₁₀ copies/mL), (C) signal-to-cutoff (S/CO) ratio values, (D) S/CO ratio values by reporter pseudovirus plaque neutralization (RVPN) titer. MAX, maximum; MIN, minimum; STD, standard deviation.

Figure 2.

Summary statistics of laboratory markers by symptoms and by visit among recruits during coronavirus disease 2019 isolation, October 14–November 23, 2020: (A) cycle threshold value, (B) subgenomic ribonucleic acid values (log₁₀ copies/mL), (C) viral load levels (log₁₀ copies/mL), (D) signal-to-cutoff ratio values.

Figure 3.

Dendrograms of hierarchical cluster analysis of laboratory results among 229 recruits at visit 1 and during follow-up. The vertical lines indicate the cut distance used to define clusters. Clusters A–D are color-coded in purple, aqua, gold, and red, respectively. (A) Cycle threshold values, visit 1, (B) cycle threshold values across visits, (C) subgenomic ribonucleic acid levels (copies/mL, log₁₀) across visits, and (D) viral load levels (copies/mL, log₁₀) across visits.

Figure 4.

Laboratory results for each recruit plotted across visits with a red line displaying the average trend for each of 4 clusters (A–D). RNA, ribonucleic acid; S/CO, signal-to-cutoff.