Results Underscore Need for Vaccination of Virus Survivors
Masked recruits assigned to Charlie Company, 1st Recruit Training Battalion, are issued gear upon arrival at Marine Corps Recruit Depot San Diego last summer. Marine recruits entered a 14-day staging period during which they were medically screened and tested for COVID-19, monitored and provided classes to prepare them to begin training. COVID-19 reinfection among some of the recruits has caused concerns. Photo by Marine Corps Cpl. Brooke C. Woods
SILVER SPRING, MD — Previous infection with COVID-19 provided some but not complete protection against reinfection in young Marine recruits, according to a new study.
Researchers from the Naval Medical Research Center and colleagues said their study underscores the importance of vaccine for patients who have recovered from novel coronavirus infection. The analysis was conducted as part of the prospective COVID-19 Health Action Response for Marines study (CHARM).
“Our findings indicate that reinfection by SARS-CoV-2 in healthy young adults is common,” explained senior author Stuart Sealfon, MD, of the Icahn School of Medicine at Mount Sinai. “”Despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. This is an important point to know and remember as vaccine rollouts continue. Young people should get the vaccine whenever possible, since vaccination is necessary to boost immune responses, prevent reinfection, and reduce transmission.”
According to the report in The Lancet Respiratory Medicine, the study, enrolled 3249 participants, between May 11, 2020, and Nov. 2, 2020, of whom 3168 (98%) continued into the two-week quarantine period. Most, 95%, of the participants—nearly all men—were then followed up during the prospective study period after quarantine for six weeks.1
Upon enrolling the participants, researchers assessed them 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. The recruits also completed a questionnaire including demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom and brief medical history.
In addition, 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 as the previous study visit. At this stage, recruits excluded if they had a positive PCR test during quarantine.
Those 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 were allowed to proceed to basic training at Marine Corps Recruit Depot, Parris Island, SC.
Three PCR tests were done at Weeks 2, 4 and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire; also tested were baseline neutralizing antibody titers on all subsequently infected seropositive and selected seropositive uninfected participants during the prospective study period.
Among 189 seropositive participants, 10% had at least one positive PCR test for SARS-CoV-2 during the six-week follow-up (1.11 cases per person-year). During the same time, 8%) of 2,247 seronegative participants tested positive (6.2 cases per person-year).
The authors calculated the incidence rate ratio at 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 titers than in those with higher baseline full-length spike protein IgG titers (hazard ratio 0.45 [95% CI 0.32–0.65]; p<0.001).
The study found that 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). The researchers advised that, among seropositive participants, baseline neutralizing titers were detected in 45 (83%) of 54 uninfected and in six (32%) of 19 infected participants during the six weeks of observation (ID50 difference p<0.0001).
“Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals,” the authors explained. “Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection. These findings might be relevant for optimization of mass vaccination strategies.”
The study pointed out that crowded living conditions, demanding regimen and requirements for personal contact during basic training despite the pandemic explained the high rate of infection at MCRDPI, adding that it is the case with all respiratory outbreaks.
Crowded Living Conditions
“The close quarters and constant contact among recruits that are needed for team building allow a viral infection to rapidly proliferate within a unit,” according to the authors. The physically and mentally demanding training environment might also suppress immunity. These factors are not typically present in the civilian community. Therefore, the study setting limits the generalizability of our findings to other settings where the frequency and intensity of exposure and the susceptibility of the host might differ.”
Researchers also noted that the two groups had similar demographic profiles, except for the higher prevalence of self-identified Hispanic and non-Hispanic Black participants in the seropositive group. In fact, they wrote, the seropositive group included almost 50% Hispanic and 22% non-Hispanic Black participants compared with 22% and 12%, respectively, in the seronegative group. “This is probably due to minority populations having higher seroprevalence rates during the COVID-19 pandemic in general and among young adults specifically,” they posited.
The study pointed out that rates of infection and the risk reduction provided by seropositivity are critical for understanding transmission dynamics for COVID-19, for epidemiological modeling and for estimating and achieving herd immunity levels. Although a major goal of mass vaccination strategies, the researchers explained, “Herd immunity is difficult to predict, if the infection risk after natural and vaccine-induced immunity is unknown. Since SARS-CoV-2 vaccines might not provide sterile immunity, it is possible that both previously infected and vaccinated individuals might later become infected. It is not known whether either can contribute to transmission events.”
They add that only a modest, approximately 10-times decrease in nares viral load as estimated by swab PCR Ct levels was present in the seropositive participants compared with the seronegative infected participants. “This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time,” the authors wrote. “The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic.”
Clinical outcomes between seropositive and seronegative groups were similar, with most, 84% and 68%, respectively, remaining asymptomatic and none requiring hospitalization. Furthermore, the two groups showed little difference in the duration of PCR positivity.
“Infection in seropositive participants was associated with lower SARS-CoV-2 IgG titers and absent or lower levels of neutralizing antibody activity,” according to the report. “Young adults have high rates of asymptomatic and pauci-symptomatic infection, which has been associated with lower levels of antibodies and potentially a less robust immune memory response.”
The result, according to the researchers, is the possibility of higher overall rates of reinfection among this population than in other populations. They added that the study was conduced among 18-20 year-old of a range of races and ethnicities and is most applicable to young male adults, cautioning, “The relative risk of infection might be different in seropositive females and in adults of other ages or health status, who might differ in immunological responses to SARS-CoV-2 infection.”
A study in seropositive compared with seronegative British healthcare workers found a nearly identical adjusted odds ratio of reinfection (0.17 [95% CI 0.13–0.24]) to that reported in Marine recruits, they added, which suggests that risk of reinfection might be similar for young adults and the general population.
Still, the authors added, “Our investigation is likely to underestimate the risk of SARS-CoV-2 infection in previously infected individuals because the seronegative group included an unknown number of previously infected participants who did not have significant IgG titers in their baseline serum sample. Despite this underestimation, we found that previously infected participants identified by seropositivity are susceptible to repeat infection, with nearly one-fifth the incidence rate of those without evidence of previous infection. This suggests that COVID-19 vaccination might be necessary for control of the pandemic in previously infected young adults.”
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Letizia AG, Ge Y, Vangeti S, Goforth C, et. Cal. SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study. The Lancet Respiratory Medicine. Published: April 15, 2021. DOI:https://doi.org/10.1016/S2213-2600(21)00158-2.
