Recurring Spatiotemporal Patterns of COVID-19 in the United States

We analyzed the waxing and waning patterns ("surges") of reported SARS-CoV-2 cases from January 1, 2020 through Oct 31, 2021 in all states and provinces (n = 93) in the USA, Mexico, and Canada, and across all counties (N = 3142) in the USA. A correlation matrix of the 576 x 576 daily case incidence rates in the 50 US states generates a distinctive "checkerboard" pattern showing that the epidemic has consisted of seven distinct internally coherent spatiotemporal wave patterns, four in the first year of the epidemic, and three thus far in the second year. Geoclustering of state case rate trajectories reveals three dominant co-varying spatial clusters of similar case rate trajectories, in the northeastern, southeastern and central/western regions of the USA. The spatiotemporal patterns of epidemic year 1 have thus far been repeated (p<.001) in epidemic year 2. The "checkerboard" pattern of the correlation matrix of case trajectories can be closely simulated as three sets of interacting sine waves with annual frequencies of 1:1:2 major cycles per year, corresponding to the northeastern, central/western, and southeastern state clusters. Case incidence patterns in Mexico and Canada have been similar to nearby regions in the southern US and the northern US, respectively. Time lapse videos allow visualization of the wave patterns. These highly structured geographical and temporal patterns, coupled with emerging evidence of annual repetition of these same patterns, show that SARS-CoV-2 case rates are driven at least in part by predictable seasonal factors. Significance StatementLocal COVID-19 rates wax and wane. Often these epidemic changes are attributed to localized human behavioral factors. Our finding of highly structured continental scale spatiotemporal patterns that cross state and national boundaries, coupled with emerging evidence of annual repetition of these same patterns, shows that COVID-19 transmission is driven at least in part by seasonal factors. Other epidemic factors such as vaccine coverage rates, or emergence of new strains like the Delta variant of SARS-CoV-2 appear to modify, but not totally eclipse, these underlying seasonal patterns. COVID-19 seasonal transmission patterns are associated with, and may be driven by, seasonal weather patterns. Predictability of these patterns can provide opportunities for forecasting the epidemic and for guiding public health preparedness and control efforts.

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery Against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques

Live oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge. Post-pyloric administration of SARS-CoV-2 by esophagogastroduodenoscopy resulted in limited virus replication in the gastrointestinal tract and minimal to no induction of mucosal antibody titers in rectal swabs, nasal swabs, and bronchoalveolar lavage. Low levels of serum neutralizing antibodies were induced and correlated with modestly diminished viral loads in nasal swabs and bronchoalveolar lavage following intranasal and intratracheal SARS-CoV-2 challenge. Overall, our data show that post-pyloric inoculation of live SARS-CoV-2 is weakly immunogenic and confers partial protection against respiratory SARS-CoV-2 challenge in rhesus macaques. ImportanceSARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations; however no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Here we report that oral administration of live SARS-CoV-2 in non-human primates may offer prophylactic benefits, but that formulation and route of administration will require further optimization.

Prominent Spatiotemporal Waves of COVID-19 Incidence in the United States: Implications for Causality, Forecasting, and Control

Better understanding of the spatiotemporal structure of the COVID-19 epidemic in the USA may help inform more effective prevention and control strategies. By analyzing daily COVID-19 case data in the United States, Mexico and Canada, we found four continental-scale epidemic wave patterns, including travelling waves, that spanned multiple state and even international boundaries. These major epidemic patterns co-varied strongly with continental-scale seasonal temperature change patterns. Geo-contiguous states shared similar timing and amplitude of epidemic wave patterns irrespective of similarities or differences in state government political party affiliations. These analyses provide evidence that seasonal factors, probably weather changes, have exerted major effects on local COVID-19 incidence rates. Seasonal wave patterns observed during the first year of the epidemic may become repeated in the subsequent years. One Sentence SummaryThe COVID-19 epidemic in the United States has consisted of four continental-scale spatiotemporal waves of case incidence that have spanned multiple states and even international boundaries.

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