Surges of serum antibodies after immunization and infection are highly specific for the offending antigen, and recent studies demonstrate that vaccines induce transient increases in circulating antibody-secreting cells (ASCs). These ASCs are highly enriched but not universally specific for the immunizing antigen, suggesting that a fraction of these ASCs could arise from polyclonal bystander stimulation of pre-existing memory cells to unrelated antigens. This model is proposed to explain maintenance of long-lived serological memory in the absence of antigen exposure. To test this model, we measure the ability of RSV and influenza virus infection or immunizations to influenza virus, tetanus toxoid, hepatitis B, and human papilloma virus to stimulate bystander memory cells specific for other major environmental antigens that represent a large fraction of the pre-existing memory B compartment. Bystander or non-specific ASC responses to RSV and tetanus could not be detected above the background levels in healthy adults, despite the presence of circulating memory B cells specific for the corresponding antigens. Non-specific ASC responses in the healthy subjects were similar to frequencies in cord blood samples. In contrast, both vaccination and infection induce massive expansion of circulating antigen-specific ASCs without significant increases in the frequencies of ASCs against unrelated antigens. Hence, non-specific stimulation of memory B cells is unlikely to contribute to the mechanisms of long-term serological memory against major human pathogens. Additionally, high specificity of circulating ASC after antigenic challenge highlight the diagnostic value of interrogating ASCs as an ideal one-time-point diagnostic immune surrogate for serology during acute infection.
Abstract. Mosquito-borne viruses are a major public health threat, but their incubation periods are typically uncited, non-specific, and not based on data. We systematically review the published literature on six mosquito-borne viruses selected for their public health importance: chikungunya, dengue, Japanese encephalitis, Rift Valley fever, West Nile, and yellow fever viruses. For each, we identify the literature's consensus on the incubation period, evaluate the evidence for this consensus, and provide detailed estimates of the incubation period and distribution based on published experimental and observational data. We abstract original data as doubly interval-censored observations. Assuming a log-normal distribution, we estimate the median incubation period, dispersion, 25th and 75th percentiles by maximum likelihood. We include bootstrapped 95% confidence intervals for each estimate. For West Nile and yellow fever viruses, we also estimate the 5th and 95th percentiles of their incubation periods.
Wastewater surveillance of SARS-CoV-2 RNA is increasingly being incorporated into public health efforts to respond to the COVID-19 pandemic. In order to obtain the maximum benefit from these efforts, approaches to wastewater monitoring need to be rapid, sensitive, and relatable to relevant epidemiological parameters. In this study, we present an ultracentrifugation-based method for the concentration of SARS-CoV-2 wastewater RNA and use crAssphage, a bacteriophage specific to the human gut, to help account for RNA loss during transit in the wastewater system and sample processing. With these methods, we were able to detect, and sometimes quantify, SARS-CoV-2 RNA from 20 mL wastewater samples within as little as 4.5 hours. Using known concentrations of bovine coronavirus RNA and deactivated SARS-CoV-2, we estimate recovery rates of approximately 7-12% of viral RNA using our method. Results from 24 sewersheds across Upstate New York during the spring and summer of 2020 suggested that stronger signals of SARS-CoV-2 RNA from wastewater may be indicative of greater COVID-19 incidence in the represented service area approximately one week in advance. SARS-CoV-2 wastewater RNA was quantifiable in some service areas with daily positives tests of less than 1 per 10,000 people or when weekly positive test rates within a sewershed were as low as 1.7%. crAssphage DNA concentrations were significantly lower during periods of high flow in almost all areas studied. After accounting for flow rate and population served, crAssphage levels per capita were estimated to be about 1.35 × 10 11 and 2.42 × 10 8 genome copies per day for DNA and RNA, respectively. A negative relationship between per capita crAssphage RNA and service area size was also observed likely reflecting degradation of RNA over long transit times. Our results reinforce the potential for wastewater surveillance to be used as a tool to supplement understanding of infectious disease transmission obtained by traditional testing and highlight the potential for crAssphage co-detection to improve interpretations of wastewater surveillance data.
Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.
Wastewater surveillance of SARS-CoV-2 has become an attractive tool for combating the spread of COVID-19 by assessing the presence or levels of the virus shed in a population. However, the methods to quantify viral RNA and to link those quantities to the level of infection within the community vary. In this study, we sought to identify and optimize scalable methods for recovery of viral nucleic acids from wastewater and attempted to use a constitutive member of the gut virome, human-specific crAssphage, to help account for unknown levels of SARS-CoV-2 decay and dilution in the wastewater infrastructure. Results suggest that ultracentrifugation of a small volume of wastewater through a 50% sucrose cushion followed by total nucleic acid extraction yielded quantifiable virus in an area with a modest number of COVID-19 cases. Further, the ratio of log10(SARS-CoV-2):log10(crAssphage) appears to be associated with the cumulative incidence of COVID-19 in the Syracuse, NY area. In areas where ultracentrifuges are available, these methods may be used to link SARS-CoV-2 quantities in wastewater to levels of transmission within communities with sewer service.
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