SARS-CoV-2 Outbreak Dynamics in an Isolated US Military Recruit Training Center With Rigorous Prevention Measures.

BACKGROUND: Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort. METHODS: Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, Marine recruits prospectively during basic training. If participants tested negative for SARS-CoV-2 by quantitative polymerase chain reaction (qPCR) at the end of quarantine, they were transferred to the training site in segregated companies and underwent biweekly testing for 6 weeks. We assessed the effects of coronavirus disease 2019 (COVID-19) prevention measures on other respiratory infections with passive surveillance data, performed phylogenetic analysis, and modeled transmission dynamics and testing regimens. RESULTS: Preventive measures were associated with drastically lower rates of other respiratory illnesses. However, among the trainees, 1,107 (44.8%) tested SARS-CoV-2-positive, with either mild or no symptoms. Phylogenetic analysis of viral genomes from 580 participants revealed that all cases but one were linked to five independent introductions, each characterized by accumulation of mutations across and within companies, and similar viral isolates in individuals from the same company. Variation in company transmission rates (mean reproduction number R 0 ; 5.5 [95% confidence interval [CI], 5.0, 6.1]) could be accounted for by multiple initial cases within a company and superspreader events. Simulations indicate that frequent rapid-report testing with case isolation may minimize outbreaks. CONCLUSIONS: Transmission of wild-type SARS-CoV-2 among Marine recruits was approximately twice that seen in the community. Insights from SARS-CoV-2 outbreak dynamics and mutations spread in a remote, congregate setting may inform effective mitigation strategies.

Serum Fc-Mediated Monocyte Phagocytosis Activity Is Stable for Several Months after SARS-CoV-2 Asymptomatic and Mildly Symptomatic Infection.

We investigated the temporal profile of multiple components of the serological response after asymptomatic or mildly symptomatic SARS-CoV-2 infection, in a cohort of 67 previously SARS-CoV-2 naive young adults, up to 8.5 months after infection. We found a significant decrease of spike IgG and neutralization antibody titers from early (11 to 56 days) to late (4 to 8.5 months) time points postinfection. Over the study period, S1-specific IgG levels declined significantly faster than that of the S2-specific IgG. Further, serum antibodies from PCR-confirmed participants cross-recognized S2, but not S1, of the betacoronaviruses HKU1 and OC43, suggesting a greater degree of cross-reactivity of S2 among betacoronaviruses. Antibody-Dependent Natural Killer cell Activation (ADNKA) was detected at the early time point but significantly decreased at the late time point. Induction of serum Antibody-Dependent Monocyte Phagocytosis (ADMP) was detected in all the infected participants, and its levels remained stable over time. Additionally, a reduced percentage of participants had detectable neutralizing activity against the Beta (50%), Gamma (61 to 67%), and Delta (90 to 94%) variants, both early and late postinfection, compared to the ancestral strain (100%). Antibody binding to S1 and RBD of Beta, Gamma, Delta (1.7 to 2.3-fold decrease), and Omicron (10 to 16-fold decrease) variants was also significantly reduced compared to the ancestral SARS-CoV-2 strain. Overall, we found variable temporal profiles of specific components and functionality of the serological response to SARS-CoV-2 in young adults, which is characterized by lasting, but decreased, neutralizing activity and antibody binding to S1, stable ADMP activity, and relatively stable S2-specific IgG levels. IMPORTANCE Adaptive immunity mediated by antibodies is important for controlling SARS-CoV-2 infection. While vaccines against COVID-19 are currently widely distributed, a high proportion of the global population is still unvaccinated. Therefore, understanding the dynamics and maintenance of the naive humoral immune response to SARS-CoV-2 is of great importance. In addition, long-term responses after asymptomatic infection are not well-characterized, given the challenges in identifying such cases. Here, we investigated the longitudinal humoral profile in a well-characterized cohort of young adults with documented asymptomatic or mildly symptomatic SARS-CoV-2 infection. By analyzing samples collected preinfection, early after infection and during late convalescence, we found that, while neutralizing activity decreased over time, high levels of serum S2 IgG and Antibody-Dependent Monocyte Phagocytosis (ADMP) activity were maintained up to 8.5 months after infection. This suggests that a subset of antibodies with specific functions could contribute to long-term protection against SARS-CoV-2 in convalescent unvaccinated individuals.

Asymptomatic or symptomatic SARS-CoV-2 infection plus vaccination confers increased adaptive immunity to variants of concern.

The ongoing evolution of SARS-CoV-2 requires monitoring the capability of immune responses to cross-recognize Variants of Concern (VOC). In this cross-sectional study, we examined serological and cell-mediated immune memory to SARS-CoV-2 variants, including Omicron, among a cohort of 18-21-year-old Marines with a history of either asymptomatic or mild SARS-CoV-2 infection 6 to 14 months earlier. Among the 210 participants in the study, 169 were unvaccinated while 41 received 2 doses of mRNA-based COVID-19 vaccines. Vaccination of previously infected participants strongly boosted neutralizing and binding activity and memory B and T cell responses including the recognition of Omicron, compared to infected but unvaccinated participants. Additionally, no measurable differences were observed in immune memory in healthy young adults with previous symptomatic or asymptomatic infections, for ancestral or variant strains. These results provide mechanistic immunological insights into population-based differences observed in immunity against Omicron and other variants among individuals with different clinical histories.

SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study.

BACKGROUND: Whether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain. We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection. METHODS: This analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18-20 years, following a 2-week unsupervised quarantine at home. After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA. Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history. SARS-CoV-2 infection was assessed by PCR at weeks 0, 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit. Participants were excluded at this stage if they had a positive PCR test during quarantine. Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot-Parris Island. Three PCR tests were done at weeks 2, 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period). FINDINGS: Between May 11, 2020, and Nov 2, 2020, we enrolled 3249 participants, of whom 3168 (98%) continued into the 2-week quarantine period. 3076 (95%) participants, 2825 (92%) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks. Among 189 seropositive participants, 19 (10%) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast, 1079 (48%) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11-0·28; p<0·001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titres than in those with higher baseline full-length spike protein IgG titres (hazard ratio 0·45 [95% CI 0·32-0·65]; p<0·001). Infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants (ORF1ab gene cycle threshold difference 3·95 [95% CI 1·23-6·67]; p=0·004). Among seropositive participants, baseline neutralising titres were detected in 45 (83%) of 54 uninfected and in six (32%) of 19 infected participants during the 6 weeks of observation (ID50 difference p<0·0001). INTERPRETATION: Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralisation activity or immunity against subsequent infection. These findings might be relevant for optimisation of mass vaccination strategies. FUNDING: Defense Health Agency and Defense Advanced Research Projects Agency.

SARS-CoV-2 Transmission among Marine Recruits during Quarantine.

BACKGROUND: The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults. METHODS: We investigated SARS-CoV-2 infections among U.S. Marine Corps recruits who underwent a 2-week quarantine at home followed by a second supervised 2-week quarantine at a closed college campus that involved mask wearing, social distancing, and daily temperature and symptom monitoring. Study volunteers were tested for SARS-CoV-2 by means of quantitative polymerase-chain-reaction (qPCR) assay of nares swab specimens obtained between the time of arrival and the second day of supervised quarantine and on days 7 and 14. Recruits who did not volunteer for the study underwent qPCR testing only on day 14, at the end of the quarantine period. We performed phylogenetic analysis of viral genomes obtained from infected study volunteers to identify clusters and to assess the epidemiologic features of infections. RESULTS: A total of 1848 recruits volunteered to participate in the study; within 2 days after arrival on campus, 16 (0.9%) tested positive for SARS-CoV-2, 15 of whom were asymptomatic. An additional 35 participants (1.9%) tested positive on day 7 or on day 14. Five of the 51 participants (9.8%) who tested positive at any time had symptoms in the week before a positive qPCR test. Of the recruits who declined to participate in the study, 26 (1.7%) of the 1554 recruits with available qPCR results tested positive on day 14. No SARS-CoV-2 infections were identified through clinical qPCR testing performed as a result of daily symptom monitoring. Analysis of 36 SARS-CoV-2 genomes obtained from 32 participants revealed six transmission clusters among 18 participants. Epidemiologic analysis supported multiple local transmission events, including transmission between roommates and among recruits within the same platoon. CONCLUSIONS: Among Marine Corps recruits, approximately 2% who had previously had negative results for SARS-CoV-2 at the beginning of supervised quarantine, and less than 2% of recruits with unknown previous status, tested positive by day 14. Most recruits who tested positive were asymptomatic, and no infections were detected through daily symptom monitoring. Transmission clusters occurred within platoons. (Funded by the Defense Health Agency and others.).