Epidemics of chikungunya, Zika, and COVID-19 reveal bias in case-based mapping

Accurate tracing of epidemic spread over space enables effective control measures. We examined three metrics of infection and disease in a pediatric cohort (N {approx} 3,000) over two chikungunya and one Zika epidemic, and in a household cohort (N=1,793) over one COVID-19 epidemic in Managua, Nicaragua. We compared spatial incidence rates (cases/total population), infection risks (infections/total population), and disease risks (cases/infected population). We used generalized additive and mixed-effects models, Kulldorfs spatial scan statistic, and intracluster correlation coefficients. Across different analyses and all epidemics, incidence rates considerably underestimated infection and disease risks, producing large and spatially non-uniform biases distinct from biases due to incomplete case ascertainment. Infection and disease risks exhibited distinct spatial patterns, and incidence clusters inconsistently identified areas of either risk. While incidence rates are commonly used to infer infection and disease risk in a population, we find that this can induce substantial biases and adversely impact policies to control epidemics. Article summary lineInferring measures of spatial risk from case-only data can substantially bias estimates, thereby weakening and potentially misdirecting measures needed to control an epidemic.

A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease

The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research. Key QuestionsO_TEXTBOXKey Questions for SARS-CoV-2 O_LIWhat are the kinetics of immune responses to infection? C_LIO_LIDo people who have more severe disease mount stronger antibody responses after infection? C_LIO_LIHow do antibody responses vary between different types of antibodies or as measured by different assays? C_LIO_LIHow does the presence of antibodies impact the clinical course and severity of the disease? C_LIO_LIIs there cross-reactivity with different coronaviruses? C_LIO_LIDoes cross-reactivity lead to cross-protection? C_LIO_LIWill infection protect you from future infection? C_LIO_LIHow long will immunity last? C_LIO_LIWhat are correlates of protection? C_LI C_TEXTBOX