Persistent memory despite rapid contraction of circulating T Cell responses to SARS-CoV-2 mRNA vaccination

Introduction While antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined. Methods Interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD). Results In two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination. Discussion Overall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

Persistent memory despite rapid contraction of circulating T Cell responses to SARS-CoV-2 mRNA vaccination.

Introduction: While antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined. Methods: Interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD). Results: In two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination. Discussion: Overall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

Comparison of adverse pregnancy and birth outcomes using archival medical records before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo: a facility-based, retrospective cohort study.

BACKGROUND: Little research has been conducted on the impact of the coronavirus disease 2019 (COVID-19) pandemic on either birth outcomes or the ability of archival medical records to accurately capture these outcomes. Our study objective is thus to compare the prevalence of preterm birth, stillbirth, low birth weight (LBW), small for gestational age (SGA), congenital microcephaly, and neonatal bloodstream infection (NBSI) before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo (DRC). METHODS: We conducted a facility-based retrospective cohort study in which identified cases of birth outcomes were tabulated at initial screening and subcategorized according to level of diagnostic certainty using Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions. Documentation of any birth complications, delivery type, and maternal vaccination history were also evaluated. The prevalence of each birth outcome was compared in the pre-COVID-19 (i.e., July 2019 to February 2020) and intra-COVID-19 (i.e., March to August 2020) periods via two-sample z-test for equality of proportions. RESULTS: In total, 14,300 birth records were abstracted. Adverse birth outcomes were identified among 22.0% and 14.3% of pregnancies in the pre-COVID-19 and intra-COVID-19 periods, respectively. For stillbirth, LBW, SGA, microcephaly, and NBSI, prevalence estimates were similar across study periods. However, the prevalence of preterm birth in the intra-COVID-19 period was significantly lower than that reported during the pre-COVID-19 period (8.6% vs. 11.5%, p < 0.0001). Furthermore, the level of diagnostic certainty declined slightly across all outcomes investigated from the pre-COVID-19 to the intra-COVID-19 period. Nonetheless, diagnostic certainty was especially low for certain outcomes (i.e., stillbirth and NBSI) regardless of period; still, other outcomes, such as preterm birth and LBW, had moderate to high levels of diagnostic certainty. Results were mostly consistent when the analysis was focused on the facilities designated for COVID-19 care. CONCLUSION: This study succeeded in providing prevalence estimates for key adverse birth outcomes using GAIA criteria during the COVID-19 pandemic in Kinshasa, DRC. Furthermore, our study adds crucial real-world data to the literature surrounding the impact of the COVID-19 pandemic on maternal and neonatal services and outcomes in Africa.

Engaging Same-Day Peer Ambassadors to Increase Coronavirus Disease 2019 Vaccination Among People Experiencing Unsheltered Homelessness in Los Angeles County: A Hybrid Feasibility-Evaluation Study.

BACKGROUND: This study aimed to evaluate the feasibility and acceptability of engaging unhoused peer ambassadors (PAs) in coronavirus disease 2019 (COVID-19) vaccination efforts to reach people experiencing unsheltered homelessness in Los Angeles County. METHODS: From August to December 2021, vaccinated PAs aged ≥18 years who could provide informed consent were recruited during vaccination events for same-day participation. Events were held at encampments, service providers (eg, housing agencies, food lines, and mobile showers), and roving locations around Los Angeles. PAs were asked to join outreach alongside community health workers and shared their experience getting vaccinated, receiving a $25 gift card for each hour they participated. Postevent surveys evaluated how many PAs enrolled and how long they participated. In October 2021, we added a preliminary effectiveness evaluation of how many additional vaccinations were attributable to PAs. Staff who enrolled the PAs estimated the number of additional people vaccinated because of talking with the PA. RESULTS: A total of 117 PAs were enrolled at 103 events, participating for an average of 2 hours. At events with the effectiveness evaluation, 197 additional people were vaccinated over 167 PA hours ($21.19 gift card cost per additional person vaccinated), accounting for >25% of all vaccines given at these events. DISCUSSION: Recruiting same-day unhoused PAs is a feasible, acceptable, and preliminarily effective technique to increase COVID-19 vaccination in unsheltered settings. The findings can inform delivery of other health services for people experiencing homelessness.

Hybrid Immunity Shifts the Fc-Effector Quality of SARS-CoV-2 mRNA Vaccine-Induced Immunity.

Despite the robust immunogenicity of SARS-CoV-2 mRNA vaccines, emerging data have revealed enhanced neutralizing antibody and T cell cross-reactivity among individuals that previously experienced COVID-19, pointing to a hybrid immune advantage with infection-associated immune priming. Beyond neutralizing antibodies and T cell immunity, mounting data point to a potential role for additional antibody effector functions, including opsinophagocytic activity, in the resolution of symptomatic COVID-19. Whether hybrid immunity modifies the Fc-effector profile of the mRNA vaccine-induced immune response remains incompletely understood. Thus, here we profiled the SARS-CoV-2 specific humoral immune response in a group of individuals with and without prior COVID-19. As expected, hybrid Spike-specific antibody titers were enhanced following the primary dose of the mRNA vaccine but were similar to those achieved by naive vaccinees after the second mRNA vaccine dose. Conversely, Spike-specific vaccine-induced Fc-receptor binding antibody levels were higher after the primary immunization in individuals with prior COVID-19 and remained higher following the second dose compared to those in naive individuals, suggestive of a selective improvement in the quality, rather than the quantity, of the hybrid humoral immune response. Thus, while the magnitude of antibody titers alone may suggest that any two antigen exposures-either hybrid immunity or two doses of vaccine alone-represent a comparable prime/boost immunologic education, we find that hybrid immunity offers a qualitatively improved antibody response able to better leverage Fc-effector functions against conserved regions of the virus. IMPORTANCE Recent data indicates improved immunity to SARS-CoV-2 in individuals who experience a combination of two mRNA vaccine doses and infection, "hybrid immunity," compared to individuals who receive vaccination or experience infection alone. While previous infection accelerates the vaccine-induced immune response following the first dose of mRNA vaccination, subsequent doses demonstrate negligible increases in antibody titers or T cell immunity. Here, using systems serology, we observed a unique antibody profile induced by hybrid immunity, marked by the unique induction of robust Fc-recruiting antibodies directed at the conserved region of the viral Spike antigen, the S2-domain, induced at lower levels in individuals who only received mRNA vaccination. Thus, hybrid immunity clearly redirects vaccine-induced immunodominance, resulting in the induction of a robust functional humoral immune response to the most highly conserved region of the SARS-CoV-2 Spike antigen, which may be key to protection against existing and emerging variants of concern. Thus, next-generation vaccines able to mimic hybrid immunity and drive a balanced response to conserved regions of the Spike antigen may confer enhanced protection against disease.

Adherence to face mask use during the COVID-19 pandemic among women seeking antenatal care in Kinshasa, Democratic Republic of Congo: a facility-based cross-sectional study.

OBJECTIVES: To describe face mask use among pregnant women seeking antenatal care (ANC) in Kinshasa, Democratic Republic of Congo and to identify factors associated with masking adherence in this population. DESIGN: Facility-based cross-sectional study nested within a prospective cohort study. SETTING: Random sample of 10 health facilities, including 5 primary health centers and 5 secondary facilities or hospitals. PARTICIPANTS: A total of 934 pregnant women aged 18 years or above with a gestational age of at least 32 weeks were consecutively surveyed from 17 August 2020 to 31 January 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the proportions of pregnant women wearing a face mask and masking correctly (ie, over the mouth and nose), and assessed their knowledge regarding the COVID-19 pandemic. Multivariable logistic regression was employed to identify factors associated with overall and correct face mask use. RESULTS: Overall, 309 (33.1%) women wore a mask during the interview after their antenatal appointments, but only 33 (10.7%) wore a mask correctly. The odds of masking and correct mask use were significantly higher among women who had their ANC visit in a facility that provided COVID-19 care. Additionally, women who experienced COVID-19-like symptoms in the past 6 months had higher odds of wearing a mask correctly compared with those reporting no recent symptoms. Although 908 (97.2%) women were aware of the COVID-19 pandemic, only 611 (67.3%) thought that COVID-19 was circulating locally in Kinshasa. CONCLUSION: Overall and correct face mask adherence levels were low among pregnant women attending ANC in Kinshasa. Our study highlights the need for improving adherence to correct face mask use in order to help control the spread of COVID-19 within Kinshasa alongside other control measures, like vaccination.

Hesitancy to receive the novel coronavirus vaccine and potential influences on vaccination among a cohort of healthcare workers in the Democratic Republic of the Congo.

Hesitancy to receive the COVID-19 vaccine among healthcare workers (HCWs) in low-resource settings, such as the Democratic Republic of the Congo (DRC), is a major global health challenge. This study identifies changes in willingness to receive vaccination among 588 HCWs in the DRC and reported influences on COVID-19 vaccination intentions. Up to 25 repeated measures were collected from participants between August 2020 to August 2021. Among the overall cohort, between August 2020 and mid-March 2021, the proportion of HCWs in each period of data collection reporting COVID-19 vaccine hesitancy ranged from 8.6% (95% CI: 5.97, 11.24) to 24.3% (95% CI: 20.12, 28.55). By early April 2021, the proportion reporting hesitancy more than doubled (52.0%; 95% CI: 46.22, 57.83). While hesitancy in the cohort began to decline by late-June 2021, 22.6% (95% CI: 18.05, 27.18) respondents indicated hesitancy in late-August 2021 which remains greater than the proportion of hesitancy at any time prior to early-March 2021. Patterns in reported influences on COVID-19 vaccination were varied with the proportion reporting some influences (e.g., no serious side effects, country of vaccine production) remaining stable throughout the year and other factors (e.g., recommendation of Ministry of Health, ease of vaccination) falling in popularity among respondents. Agreement that the national vaccination schedule should be followed apart from the COVID-19 vaccine remained high among respondents throughout the study period. This study shows that, among a cohort of HCWs in the DRC who have likely been influenced by regional, national, and global factors, COVID-19 vaccine hesitancy has fluctuated during the pandemic and should not be treated as a static factor. Additional research to determine which factors most influence HCWs' willingness to receive the COVID-19 vaccine offers opportunities to reduce vaccine hesitancy among this important population through tailored public health messaging.

Dominant CD8+ T Cell Nucleocapsid Targeting in SARS-CoV-2 Infection and Broad Spike Targeting From Vaccination.

CD8+ T cells have key protective roles in many viral infections. While an overall Th1-biased cellular immune response against SARS-CoV-2 has been demonstrated, most reports of anti-SARS-CoV-2 cellular immunity have evaluated bulk T cells using pools of predicted epitopes, without clear delineation of the CD8+ subset and its magnitude and targeting. In recently infected persons (mean 29.8 days after COVID-19 symptom onset), we confirm a Th1 bias (and a novel IL-4-producing population of unclear significance) by flow cytometry, which does not correlate to antibody responses against the receptor binding domain. Evaluating isolated CD8+ T cells in more detail by IFN-γ ELISpot assays, responses against spike, nucleocapsid, matrix, and envelope proteins average 396, 901, 296, and 0 spot-forming cells (SFC) per million, targeting 1.4, 1.5, 0.59, and 0.0 epitope regions respectively. Nucleocapsid targeting is dominant in terms of magnitude, breadth, and density of targeting. The magnitude of responses drops rapidly post-infection; nucleocapsid targeting is most sustained, and vaccination selectively boosts spike targeting. In SARS-CoV-2-naïve persons, evaluation of the anti-spike CD8+ T cell response soon after vaccination (mean 11.3 days) yields anti-spike CD8+ T cell responses averaging 2,463 SFC/million against 4.2 epitope regions, and targeting mirrors that seen in infected persons. These findings provide greater clarity on CD8+ T cell anti-SARS-CoV-2 targeting, breadth, and persistence, suggesting that nucleocapsid inclusion in vaccines could broaden coverage and durability.

Assessing the feasibility of passive surveillance for maternal immunization safety utilizing archival medical records in Kinshasa, Democratic Republic of the Congo.

INTRODUCTION: Since the establishment of the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions in 2015, there has been an urgent need for field validation of pharmacovigilance feasibility in low- and middle-income countries. In this study, we assess the availability and quality of archival medical records at ten randomly selected high-traffic maternity wards in Kinshasa province, Democratic Republic of Congo (DRC). METHODS: A retrospective cohort of mother-child pairs was established from all recorded births taking place at study sites between July 1, 2019 to February 28, 2020 through digitization of medical records. Adverse birth outcomes and maternal vaccination status, where available and linkable, were defined according to GAIA. Basic demographic information on mothers and newborns was also tabulated; birth outcomes were assessed for both intra-site prevalence and a pooled prevalence. RESULTS: A total of 7,697 mother-newborn pair records were extracted, with 37% of infants screening positive as cases of adverse outcomes. Maternal vaccination information was linkable to 67% of those cases. In total, 51% of stillbirths, 98% of preterm births, 100% of low birthweight infants, 90% of small for gestational age infants, 100% of microcephalic infants, and 0% of neonatal bloodstream infections were classifiable according to GAIA standards following initial screening. Forty percent of case mothers had some indication of tetanus vaccination prior to delivery in their medical records, but only 26% of case mothers met some level of GAIA definition for maternal vaccination during the pregnancy of interest. CONCLUSIONS: Archival birth records from delivery centers can be feasibly utilized to screen for stillbirth and maternal tetanus vaccination, and to accurately classify preterm birth, low birthweight, small for gestational age, and congenital microcephaly. Assessment of other neonatal outcomes were limited by inconsistent postpartum infant follow-up and records keeping.

Wildlife in Cameroon harbor diverse coronaviruses, including many closely related to human coronavirus 229E.

Zoonotic spillover of animal viruses into human populations is a continuous and increasing public health risk. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the global impact of emergence. Considering the history and diversity of coronaviruses (CoVs), especially in bats, SARS-CoV-2 will likely not be the last to spillover from animals into human populations. We sampled and tested wildlife in the Central African country Cameroon to determine which CoVs are circulating and how they relate to previously detected human and animal CoVs. We collected animal and ecological data at sampling locations and used family-level consensus PCR combined with amplicon sequencing for virus detection. Between 2003 and 2018, samples were collected from 6,580 animals of several different orders. CoV RNA was detected in 175 bats, a civet, and a shrew. The CoV RNAs detected in the bats represented 17 different genetic clusters, coinciding with alpha (n = 8) and beta (n = 9) CoVs. Sequences resembling human CoV-229E (HCoV-229E) were found in 40 Hipposideridae bats. Phylogenetic analyses place the human-derived HCoV-229E isolates closest to those from camels in terms of the S and N genes but closest to isolates from bats for the envelope, membrane, and RNA-dependent RNA polymerase genes. The CoV RNA positivity rate in bats varied significantly (P < 0.001) between the wet (8.2 per cent) and dry seasons (4.5 per cent). Most sampled species accordingly had a wet season high and dry season low, while for some the opposite was found. Eight of the suspected CoV species of which we detected RNA appear to be entirely novel CoV species, which suggests that CoV diversity in African wildlife is still rather poorly understood. The detection of multiple different variants of HCoV-229E-like viruses supports the bat reservoir hypothesis for this virus, with the phylogenetic results casting some doubt on camels as an intermediate host. The findings also support the previously proposed influence of ecological factors on CoV circulation, indicating a high level of underlying complexity to the viral ecology. These results indicate the importance of investing in surveillance activities among wild animals to detect all potential threats as well as sentinel surveillance among exposed humans to determine emerging threats.

Longitudinal Assessment of Coronavirus Disease 2019 Vaccine Acceptance and Uptake Among Frontline Medical Workers in Los Angeles, California.

BACKGROUND: Sentiments of vaccine hesitancy and distrust in public health institutions have complicated the government-led coronavirus disease 2019 (COVID-19) vaccine control strategy in the United States. As the first to receive the vaccine, COVID-19 vaccine attitudes among frontline workers are consequential for COVID-19 control and public opinion of the vaccine. METHODS: In this study, we used a repeated cross-sectional survey administered at 3 time points between 24 September 2020 and 6 February 2021 to a cohort of employees of the University of California, Los Angeles Health and the Los Angeles County Fire Department. The primary outcome of interest was COVID-19 vaccination intent and vaccine uptake. RESULTS: Confidence in COVID-19 vaccines and vaccine uptake rose significantly over time. At survey 1, confidence in vaccine protection was 46.4% among healthcare workers (HCWs) and 34.6% among first responders (FRs); by survey 3, this had risen to 90.0% and 75.7%, respectively. At survey 1, about one-third of participants intended to receive a vaccine as soon as possible. By survey 3, 96.0% of HCWs and 87.5% of FRs had received a COVID-19 vaccine. CONCLUSIONS: Attitudes toward vaccine uptake increased over the study period, likely a result of increased public confidence in COVID-19 vaccines, targeted communications, a COVID-19 winter surge in Los Angeles County, and ease of access from employer-sponsored vaccine distribution.

Humoral responses to SARS-CoV-2 mRNA vaccines: Role of past infection.

Two mRNA vaccines (BNT162b2 and mRNA-1273) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are globally authorized as a two-dose regimen. Understanding the magnitude and duration of protective immune responses is vital to curbing the pandemic. We enrolled 461 high-risk health services workers at the University of California, Los Angeles (UCLA) and first responders in the Los Angeles County Fire Department (LACoFD) to assess the humoral responses in previously infected (PI) and infection naïve (NPI) individuals to mRNA-based vaccines (BNT162b2/Pfizer- BioNTech or mRNA-1273/Moderna). A chemiluminescent microparticle immunoassay was used to detect antibodies against SARS-CoV-2 Spike in vaccinees prior to (n = 21) and following each vaccine dose (n = 246 following dose 1 and n = 315 following dose 2), and at days 31-60 (n = 110) and 61-90 (n = 190) following completion of the 2-dose series. Both vaccines induced robust antibody responses in all immunocompetent individuals. Previously infected individuals achieved higher median peak titers (p = 0.002) and had a slower rate of decay (p = 0.047) than infection-naïve individuals. mRNA-1273 vaccinated infection-naïve individuals demonstrated modestly higher titers following each dose (p = 0.005 and p = 0.029, respectively) and slower rates of antibody decay (p = 0.003) than those who received BNT162b2. A subset of previously infected individuals (25%) required both doses in order to reach peak antibody titers. The biologic significance of the differences between previously infected individuals and between the mRNA-1273 and BNT162b2 vaccines remains uncertain, but may have important implications for booster strategies.

Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses.

Studies of two SARS-CoV-2 mRNA vaccines suggested that they yield ∼95% protection from symptomatic infection at least short-term, but important clinical questions remain. It is unclear how vaccine-induced antibody levels quantitatively compare to the wide spectrum induced by natural SARS-CoV-2 infection. Vaccine response kinetics and magnitudes in persons with prior COVID-19 compared to virus-naïve persons are not well-defined. The relative stability of vaccine-induced versus infection-induced antibody levels is unclear. We addressed these issues with longitudinal assessments of vaccinees with and without prior SARS-CoV-2 infection using quantitative enzyme-linked immunosorbent assay (ELISA) of anti-RBD antibodies. SARS-CoV-2-naïve individuals achieved levels similar to mild natural infection after the first vaccination; a second dose generated levels approaching severe natural infection. In persons with prior COVID-19, one dose boosted levels to the high end of severe natural infection even in those who never had robust responses from infection, increasing no further after the second dose. Antiviral neutralizing assessments using a spike-pseudovirus assay revealed that virus-naïve vaccinees did not develop physiologic neutralizing potency until the second dose, while previously infected persons exhibited maximal neutralization after one dose. Finally, antibodies from vaccination waned similarly to natural infection, resulting in an average of ∼90% loss within 90 days. In summary, our findings suggest that two doses are important for quantity and quality of humoral immunity in SARS-CoV-2-naïve persons, while a single dose has maximal effects in those with past infection. Antibodies from vaccination wane with kinetics very similar to that seen after mild natural infection; booster vaccinations will likely be required.

Coronavirus surveillance in wildlife from two Congo basin countries detects RNA of multiple species circulating in bats and rodents.

Coronaviruses play an important role as pathogens of humans and animals, and the emergence of epidemics like SARS, MERS and COVID-19 is closely linked to zoonotic transmission events primarily from wild animals. Bats have been found to be an important source of coronaviruses with some of them having the potential to infect humans, with other animals serving as intermediate or alternate hosts or reservoirs. Host diversity may be an important contributor to viral diversity and thus the potential for zoonotic events. To date, limited research has been done in Africa on this topic, in particular in the Congo Basin despite frequent contact between humans and wildlife in this region. We sampled and, using consensus coronavirus PCR-primers, tested 3,561 wild animals for coronavirus RNA. The focus was on bats (38%), rodents (38%), and primates (23%) that posed an elevated risk for contact with people, and we found coronavirus RNA in 121 animals, of which all but two were bats. Depending on the taxonomic family, bats were significantly more likely to be coronavirus RNA-positive when sampled either in the wet (Pteropodidae and Rhinolophidae) or dry season (Hipposideridae, Miniopteridae, Molossidae, and Vespertilionidae). The detected RNA sequences correspond to 15 alpha- and 6 betacoronaviruses, with some of them being very similar (>95% nucleotide identities) to known coronaviruses and others being more unique and potentially representing novel viruses. In seven of the bats, we detected RNA most closely related to sequences of the human common cold coronaviruses 229E or NL63 (>80% nucleotide identities). The findings highlight the potential for coronavirus spillover, especially in regions with a high diversity of bats and close human contact, and reinforces the need for ongoing surveillance.

Pandemic velocity: Forecasting COVID-19 in the US with a machine learning & Bayesian time series compartmental model.

Predictions of COVID-19 case growth and mortality are critical to the decisions of political leaders, businesses, and individuals grappling with the pandemic. This predictive task is challenging due to the novelty of the virus, limited data, and dynamic political and societal responses. We embed a Bayesian time series model and a random forest algorithm within an epidemiological compartmental model for empirically grounded COVID-19 predictions. The Bayesian case model fits a location-specific curve to the velocity (first derivative) of the log transformed cumulative case count, borrowing strength across geographic locations and incorporating prior information to obtain a posterior distribution for case trajectories. The compartmental model uses this distribution and predicts deaths using a random forest algorithm trained on COVID-19 data and population-level characteristics, yielding daily projections and interval estimates for cases and deaths in U.S. states. We evaluated the model by training it on progressively longer periods of the pandemic and computing its predictive accuracy over 21-day forecasts. The substantial variation in predicted trajectories and associated uncertainty between states is illustrated by comparing three unique locations: New York, Colorado, and West Virginia. The sophistication and accuracy of this COVID-19 model offer reliable predictions and uncertainty estimates for the current trajectory of the pandemic in the U.S. and provide a platform for future predictions as shifting political and societal responses alter its course.

Controlling emerging zoonoses at the animal-human interface.

BACKGROUND: For many emerging or re-emerging pathogens, cases in humans arise from a mixture of introductions (via zoonotic spillover from animal reservoirs or geographic spillover from endemic regions) and secondary human-to-human transmission. Interventions aiming to reduce incidence of these infections can be focused on preventing spillover or reducing human-to-human transmission, or sometimes both at once, and typically are governed by resource constraints that require policymakers to make choices. Despite increasing emphasis on using mathematical models to inform disease control policies, little attention has been paid to guiding rational disease control at the animal-human interface. METHODS: We introduce a modeling framework to analyze the impacts of different disease control policies, focusing on pathogens exhibiting subcritical transmission among humans (i.e. pathogens that cannot establish sustained human-to-human transmission). We quantify the relative effectiveness of measures to reduce spillover (e.g. reducing contact with animal hosts), human-to-human transmission (e.g. case isolation), or both at once (e.g. vaccination), across a range of epidemiological contexts. RESULTS: We provide guidelines for choosing which mode of control to prioritize in different epidemiological scenarios and considering different levels of resource and relative costs. We contextualize our analysis with current zoonotic pathogens and other subcritical pathogens, such as post-elimination measles, and control policies that have been applied. CONCLUSIONS: Our work provides a model-based, theoretical foundation to understand and guide policy for subcritical zoonoses, integrating across disciplinary and species boundaries in a manner consistent with One Health principles.

An evidence review of face masks against COVID-19.

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.