Clinical and Economic Impact of COVID-19 on Agricultural Workers, Guatemala1.

We evaluated clinical and socioeconomic burdens of respiratory disease in banana farm workers in Guatemala. We offered all eligible workers enrollment during June 15-December 30, 2020, and annually, then tracked them for influenza-like illnesses (ILI) through self-reporting to study nurses, sentinel surveillance at health posts, and absenteeism. Workers who had ILI submitted nasopharyngeal swab specimens for testing for influenza virus, respiratory syncytial virus, and SARS-CoV-2, then completed surveys at days 0, 7, and 28. Through October 10, 2021, a total of 1,833 workers reported 169 ILIs (12.0 cases/100 person-years), and 43 (25.4%) were laboratory-confirmed infections with SARS-CoV-2 (3.1 cases/100 person-years). Workers who had SARS-CoV-2‒positive ILIs reported more frequent anosmia, dysgeusia, difficulty concentrating, and irritability and worse clinical and well-being severity scores than workers who had test result‒negative ILIs. Workers who had positive results also had greater absenteeism and lost income. These results support prioritization of farm workers in Guatemala for COVID-19 vaccination.

Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting.

INTRODUCTION: This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling-a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals. METHODS AND ANALYSIS: In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests. ETHICS AND DISSEMINATION: This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions-and ultimately to assist with keeping congregate settings open that are essential for our social fabric. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (#NCT05145803).

High SARS-CoV-2 Seroprevalence and Rapid Neutralizing Antibody Decline among Agricultural Workers in Rural Guatemala, June 2020-March 2021.

Essential agricultural workers work under occupational conditions that may increase the risk of SARS-CoV-2 exposure and transmission. Data from an agricultural worker cohort in Guatemala, and anti-SARS-CoV-2 nucleocapsid IgG (anti-N IgG) testing were used to estimate past infections and analyze risk factors associated with seropositivity at enrollment and association with SARS-CoV-2 infection. The stability of neutralizing antibody (NAb) responses were assessed in a subset of participants. The adjusted relative risk (aRR) for seroprevalence at enrollment was estimated accounting for correlations within worksites. At enrollment, 616 (46.2%) of 1334 (93.2%) participants had anti-N IgG results indicating prior SARS-CoV-2 infection. A cough ≤ 10 days prior to enrollment (aRR = 1.28, 95% CI: 1.13-1.46) and working as a packer (aRR = 2.00, 95% CI: 1.67-2.38) or packing manager within the plants (aRR = 1.82, 95% CI: 1.36-2.43) were associated with increased risk of seropositivity. COVID-19 incidence density among seronegative workers was 2.3/100 Person-Years (P-Y), higher than seropositive workers (0.4/100 P-Y). Most workers with follow-up NAb testing (65/77, 84%) exhibited a 95% average decrease in NAb titers in <6 months. While participants seropositive at baseline were less likely to experience a symptomatic SARS-CoV-2 infection during follow-up, NAb titers rapidly waned, underscoring the need for multipronged COVID-19 prevention strategies in the workplace, including vaccination.

Drugsniffer: An Open Source Workflow for Virtually Screening Billions of Molecules for Binding Affinity to Protein Targets.

The SARS-CoV2 pandemic has highlighted the importance of efficient and effective methods for identification of therapeutic drugs, and in particular has laid bare the need for methods that allow exploration of the full diversity of synthesizable small molecules. While classical high-throughput screening methods may consider up to millions of molecules, virtual screening methods hold the promise of enabling appraisal of billions of candidate molecules, thus expanding the search space while concurrently reducing costs and speeding discovery. Here, we describe a new screening pipeline, called drugsniffer, that is capable of rapidly exploring drug candidates from a library of billions of molecules, and is designed to support distributed computation on cluster and cloud resources. As an example of performance, our pipeline required ∼40,000 total compute hours to screen for potential drugs targeting three SARS-CoV2 proteins among a library of ∼3.7 billion candidate molecules.

Antibody and T cell responses to COVID-19 vaccination in patients receiving anticancer therapies.

BACKGROUND: Patients with cancer were excluded from phase 3 COVID-19 vaccine trials, and the immunogenicity and side effect profiles of these vaccines in this population is not well understood. Patients with cancer can be immunocompromised from chemotherapy, corticosteroids, or the cancer itself, which may affect cellular and/or humoral responses to vaccination. PD-1 is expressed on T effector cells, T follicular helper cells and B cells, leading us to hypothesize that anti-PD-1 immunotherapies may augment antibody or T cell generation after vaccination. METHODS: Antibodies to the SARS-CoV-2 receptor binding domain (RBD) and spike protein were assessed in patients with cancer (n=118) and healthy donors (HD, n=22) after 1, 2 or 3 mRNA vaccine doses. CD4+ and CD8+ T cell reactivity to wild-type (WT) or B.1.617.2 (delta) spike peptides was measured by intracellular cytokine staining. RESULTS: Oncology patients without prior COVID-19 infections receiving immunotherapy (n=36), chemotherapy (n=15), chemoimmunotherapy (n=6), endocrine or targeted therapies (n=6) and those not on active treatment (n=26) had similar RBD and Spike IgG antibody titers to HDs after two vaccinations. Contrary to our hypothesis, PD-1 blockade did not augment antibody titers or T cell responses. Patients receiving B-cell directed therapies (n=14) including anti-CD20 antibodies and multiple myeloma therapies had decreased antibody titers, and 9/14 of these patients were seronegative for RBD antibodies. No differences were observed in WT spike-reactive CD4+ and CD8+ T cell generation between treatment groups. 11/13 evaluable patients seronegative for RBD had a detectable WT spike-reactive CD4+ T cell response. T cells cross-reactive against the B.1.617.2 variant spike peptides were detected in 31/59 participants. Two patients with prior immune checkpoint inhibitor-related adrenal insufficiency had symptomatic hypoadrenalism after vaccination. CONCLUSIONS: COVID-19 vaccinations are safe and immunogenic in patients with solid tumors, who developed similar antibody and T cell responses compared with HDs. Patients on B-cell directed therapies may fail to generate RBD antibodies after vaccination and should be considered for prophylactic antibody treatments. Many seronegative patients do develop a T cell response, which may have an anti-viral effect. Patients with pre-existing adrenal insufficiency may need to take stress dose steroids during vaccination to avoid adrenal crisis.

Perceived roles, benefits and barriers of virtual global health partnership initiatives: a cross-sectional exploratory study.

BACKGROUND: Virtual global health partnership initiatives (VGHPIs) evolved rapidly during the COVID-19 pandemic to ensure partnership continuity. However the current landscape for VGHPI use and preference is unknown. This study aimed to increase understanding of GH partners' perspectives on VGHPIs. METHODS: From 15 October to 30 November 2020, An online, international survey was conducted using snowball sampling to document pandemic-related changes in partnership activities, preferences for VGHPIs, and perceived acceptability and barriers. The survey underwent iterative development within a diverse author group, representing academic and clinical institutions, and the non-profit sector. Participants from their professional global health networks were invited, including focal points for global health partnerships while excluding trainees and respondents from the European Economic Area. Analysis stratified responses by country income classification and partnership type. Authors used descriptive statistics to characterize responses, defining statistical significance as α = 0.05. RESULTS: A total of 128 respondents described 219 partnerships. 152/219 (69%) partnerships were transnational, 157/219 (72%) were of > 5 years duration, and 127/219 (60%) included bidirectional site visits. High-income country (HIC) partners sent significantly more learners to low- to middle-income country (LMIC) partner sites (p < 0.01). Participants commented on pandemic-related disruptions affecting 217/219 (99%) partnerships; 195/217 (90%) were disruption to activities; 122/217 (56%) to communication; 73/217 (34%) to access to professional support; and 72/217 (33%) to funding. Respondents indicated that VGHPIs would be important to 206/219 (94%) of their partnerships moving forward. There were overall differences in resource availability, technological capacity, and VGHPI preferences between LMIC and HIC respondents, with a statistically significant difference in VGHPI acceptability (p < 0.001). There was no significant difference between groups regarding VGHPIs' perceived barriers. CONCLUSIONS: The pandemic disrupted essential partnership elements, compounding differences between LMIC and HIC partners in their resources and preferences for partnership activities. VGHPIs have the potential to bridge new and existing gaps and maximize gains, bi-directionality, and equity in partnerships during and after COVID-19.

COVID-19, Influenza and RSV: Surveillance-informed prevention and treatment - Meeting report from an isirv-WHO virtual conference.

The International Society for Influenza and other Respiratory Virus Diseases (isirv) and the WHO held a joint virtual conference from 19th-21st October 2021. While there was a major focus on the global response to the SARS-CoV-2 pandemic, including antivirals, vaccines and surveillance strategies, papers were also presented on treatment and prevention of influenza and respiratory syncytial virus (RSV). Potential therapeutics for SARS-CoV-2 included host-targeted therapies baricitinib, a JAK inhibitor, tocilizumab, an IL-6R inhibitor, verdinexor and direct acting antivirals ensovibep, S-217622, AT-527, and monoclonal antibodies casirivimab and imdevimab, directed against the spike protein. Data from trials of nirsevimab, a monoclonal antibody with a prolonged half-life which binds to the RSV F-protein, and an Ad26.RSV pre-F vaccine were also presented. The expanded role of the WHO Global Influenza Surveillance and Response System to address the SARS-CoV-2 pandemic was also discussed. This report summarizes the oral presentations given at this meeting for the benefit of the broader medical and scientific community involved in surveillance, treatment and prevention of respiratory virus diseases.

Seasonal Influenza Prevention and Control Progress in Latin America and the Caribbean in the Context of the Global Influenza Strategy and the COVID-19 Pandemic.

Each year in Latin America and the Caribbean, seasonal influenza is associated with an estimated 36,500 respiratory deaths and 400,000 hospitalizations. Since the 2009 influenza A(H1N1) pandemic, the Region has made significant advances in the prevention and control of seasonal influenza, including improved surveillance systems, burden estimates, and vaccination of at-risk groups. The Global Influenza Strategy 2019-2030 provides a framework to strengthen these advances. Against the backdrop of this new framework, the University of Colorado convened in October 2020 its Immunization Advisory Group of Experts to review and discuss current surveillance, prevention, and control strategies for seasonal influenza in Latin America and the Caribbean, also in the context of the COVID-19 pandemic. This review identified five areas for action and made recommendations specific to each area. The Region should continue its efforts to strengthen surveillance and impact evaluations. Existing data on disease burden, seasonality patterns, and vaccination effectiveness should be used to inform decision-making at the country level as well as advocacy efforts for programmatic resources. Regional and country strategic plans should be prepared and include specific targets for 2030. Existing investments in influenza prevention and control, including for immunization programs, should be optimized. Finally, regional partnerships, such as the regional networks for syndromic surveillance and vaccine effectiveness evaluation (SARInet and REVELAC-i), should continue to play a critical role in continuous learning and standardization by sharing experiences and best practices among countries.

Pre-Coronavirus Disease 2019 Telehealth Practices Among Pediatric Infectious Diseases Specialists in the United States.

BACKGROUND: Telehealth (TH) practices among pediatric infectious disease (PID) specialists prior to the coronavirus disease 2019 (COVID-19) pandemic are largely unknown. METHODS: In 2019, the Pediatric Infectious Diseases Society (PIDS) Telehealth Working Group surveyed PIDS members to collect data on the use of TH modalities, adoption barriers, interest, extent of curbside consultations (CCs), and reimbursement. RESULTS: Of 1213 PIDS members, 161 (13.3%) completed the survey, and the responses of 154 (12.7%) from the United States were included in our report. Medical school (63.6%) and hospital (44.8%) were the commonest work settings with 16.9% practicing in both of them. The most common TH modalities used were synchronous provider-patient virtual visits (20.8%) and synchronous provider-provider consultations (13.6%). TH services included outpatient consultations (48.1%), vaccine recommendations (43.5%), inpatient consultations (39.6%), and travel advice (39.6%). Barriers perceived by respondents included reimbursement (55.8%), lack of experience with TH (55.2%), lack of institutional support (52.6%), lack of administrative support (50%), and cost of implementation (48.7%). Most of the respondents (144, 93.5%) were interested in implementing a wide range of TH modalities. CCs accounted for 1-20 hours/week among 148 respondents. CONCLUSIONS: Most of the PIDS survey respondents reported low utilization of TH and several perceived barriers to TH adoption before the COVID-19 pandemic. Nonetheless, they expressed a strong interest in adopting different TH modalities. They also reported spending considerable time on non-reimbursed CCs from within and outside their institutions. The results of this survey provide baseline information that will allow comparisons with post-COVID-19 changes in the adoption of TH in PID.

Ophthalmic manifestations of coronavirus disease 2019 and ocular side effects of investigational pharmacologic agents.

PURPOSE OF REVIEW: To compile and report the ocular manifestations of coronavirus disease 2019 (COVID-19) infection and summarize the ocular side effects of investigational treatments of this disease. RECENT FINDINGS: Conjunctivitis is by far the most common ocular manifestation of COVID-19 with viral particles being isolated from tears/secretions of infected individuals. Multiple therapeutic options are being explored across a variety of medication classes with diverse ocular side effects. SUMMARY: Eye care professionals must exercise caution, as conjunctivitis may be the presenting or sole finding of an active COVID-19 infection. While no currently studied therapeutic agents have been found to reliably treat COVID-19, early vaccination trials are progressing and show promise. A video abstract is available for a more detailed summary. VIDEO ABSTRACT: http://links.lww.com/COOP/A36.