ABSTRACT
Background. Infection with SARS-CoV-2 and the resulting host immune response has been primarily characterized in middle and older aged populations due to a higher incidence of symptoms in these age groups. Due to reduced severity of disease, children were poorly studied and assumed to be less frequently infected compared to older age groups. We measured the viral load and adaptive immune response across the age-spectrum to define the age-dependent viral and host responses. Methods. From March 2020-March 2022, we enrolled individuals across the age spectrum who presented to U.S. military medical treatment facilities with COVID-19-like symptoms. In this longitudinal cohort study, demographic and clinical data were collected in addition to nasopharyngeal swabs and peripheral blood. Magnitude of viral RNA was measured by quantitative PCR (qPCR) from nasopharyngeal samples and SARS-CoV-2-specific IgG antibodies were measured from blood with multiplex microsphere immunoassays. Results. 4,768 SARS-CoV-2 positive participants were enrolled, among whom 42, 64, 89, 380, 948 and 245 individuals were in age brackets 0-4y, 5-11y, 12-17y, 18-44, 45-64y, and >65y, respectively. Viral load as measured by qPCR was determined to be similar across age groups within the first week post symptom onset. The magnitude of the IgG antibody response against the spike protein was also compared across age groups at early and convalescent time points and was higher in those over the age of 65 years. Conclusion. Early viral load during acute infection did not correlate with age in individuals who experienced COVID-19. These findings diverge from other respiratory viruses, such as respiratory syncytial virus and influenza where children tend to have higher viral loads. In contrast, the magnitude of the antibody response against the spike protein correlated with older age at acute and convalescent time points. Together our data suggest that the host response against SAR-CoV-2 differs with age and is not associated with the acute viral load. Defining age-dependent immunity against SARS-CoV-2 has the potential to identify key immunologic responses that can be used to optimize treatment and vaccine strategies.
ABSTRACT
Background. Omicron SARS-CoV-2 infections are associated with less frequent olfactory sensory loss and a predominance of pharyngitis symptoms compared to prior variants, with proposed diagnostic implications. We examined whether such symptomology predicts a higher RNA abundance in the oropharynx. We further investigated how age, symptom-day, vaccination history and clinical severity correlate with viral load to inform clinical prognostication and transmission modeling. Methods. The EPICC study is a longitudinal cohort of COVID-19 cases enrolled through U.S military medical treatment facilities. Demographic and clinical characteristics were measured with interviews and surveys. Nasopharyngeal (NP), oropharyngeal (OP) and nasal swabs (NS) were collected for SARS-CoV-2 qPCR and sequence genotyping. Multivariable linear regression models were fit to estimate the effect of anatomical site on SARS-CoV-2 RNA abundance (a proxy for viral load), adjusting for sampling time, vaccine history and host age. Results. We analyzed 77 sequence-confirmed Omicron cases;no BA.2 cases were detected. The median age was 38.8 years. 81.8% were vaccinated and 15.6% cases were hospitalized. 80.0%, 21.8%, and 65.5% reported nasal congestion, loss of smell or taste, and sore throat, respectively. The median RNA abundance was lowest in OP swabs (p < 0.001) (Fig 1). Linear regression confirmed that OP sampling was associated with lower viral load (p < 0.001). We further noted that greater age and symptom-day were independent correlates of viral load (Table 1). By bivariate analysis there was a trend toward lower RNA abundance in vaccinated subjects (p = 0.35). RNA abundance (at any site) was substantially higher in hospitalized (10634 N2 genome equivalents [GE]/reaction) versus outpatient cases (1419 N1 GE/reaction) but this was not statistically significant (p = 0.26). Conclusion. We noted prevalent sore throat symptoms and infrequent sensory loss in Omicron cases. Despite this, viral load was highest in NP/NS collected swabs as has been noted in prior variants. We note an age correlation with RNA abundance, and provide a viral load decay rate which may be useful for transmission modeling. Vaccination and clinical severity may also correlate with Omicron viral load, as noted with prior SARS-CoV-2 variants.
ABSTRACT
Background. COVID-19 may have deleterious effects on the fitness of active duty US military service members. We seek to understand the long-term functional consequences of SARS-CoV-2 infection in this critical population, and in other military healthcare beneficiaries. Methods. The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal cohort study to describe the outcomes of SARS-CoV-2 infection in US Military Health System beneficiaries. Subjects provided information about difficulties experienced with daily activities, exercise, and physical fitness performance via electronic surveys. Subjects completed surveys at enrollment and at 1, 3, 6, 9, and 12 months. Results. 5,910 subjects completed survey fitness questions, 3,244 (55%) of whom tested SARS-CoV-2 positive at least once during the period of observation. Over 75% of subjects were young adults and over half were male (Table 1). 1,093 (34.3%) of SARS-CoV-2-positive subjects reported new or increased difficulty exercising compared to 393 (14.8%) SARS-CoV-2 negative subjects (p < 0.01) (Table 2). The most commonly reported symptoms related to problems with exercise and activities were dyspnea and fatigue.Among the active-duty members who answered the question about their service-mandated physical fitness test scores, 43.2% of SARS-CoV-2-positive participants reported that their scores had worsened in the study period, compared with 24.3%of SARS-CoV-2 negative participants.Among SARS-CoV-2-positive subjects, reports of difficulty exercising and performing daily activities were highest within one month of the first positive test, decreasing in prevalence among the cohort only slightly to 24% and 18%, respectively, at 12 months (Figure 1). Conclusion. A substantial proportion of military service-members in this cohort have reported impairment of their service-mandated physical fitness scores after COVID-19;this proportion is significantly higher than those who are SARS-CoV-2 negative and persists to 12 months in many;similar complaints were reported among non-active duty. Further objective evaluation of post-COVID fitness impairment in this population is warranted. (Figure Presented).