The effects of cash transfers on adult and child mortality in low- and middle-income countries.

Poverty is an important social determinant of health that is associated with increased risk of death1-5. Cash transfer programmes provide non-contributory monetary transfers to individuals or households, with or without behavioural conditions such as children's school attendance6,7. Over recent decades, cash transfer programmes have emerged as central components of poverty reduction strategies of many governments in low- and middle-income countries6,7. The effects of these programmes on adult and child mortality rates remains an important gap in the literature, however, with existing evidence limited to a few specific conditional cash transfer programmes, primarily in Latin America8-14. Here we evaluated the effects of large-scale, government-led cash transfer programmes on all-cause adult and child mortality using individual-level longitudinal mortality datasets from many low- and middle-income countries. We found that cash transfer programmes were associated with significant reductions in mortality among children under five years of age and women. Secondary heterogeneity analyses suggested similar effects for conditional and unconditional programmes, and larger effects for programmes that covered a larger share of the population and provided larger transfer amounts, and in countries with lower health expenditures, lower baseline life expectancy, and higher perceived regulatory quality. Our findings support the use of anti-poverty programmes such as cash transfers, which many countries have introduced or expanded during the COVID-19 pandemic, to improve population health.

Durability of SARS-CoV-2 mRNA Booster Vaccine Protection Against Omicron Among Health Care Workers with a Vaccine Mandate.

BACKGROUND: The SARS-CoV-2 Omicron Variant has spread rapidly throughout the world since being identified in South Africa in November 2021. Few studies have assessed primary series and booster vaccine effectiveness against Omicron among US health care workers. METHODS: We conducted a test-negative case-control design to estimate BNT162b2 and mRNA1273 primary vaccination and booster effectiveness against SARS-CoV-2 infection and symptomatic Covid-19 during an Omicron surge among employees of the University of Pennsylvania Health System. The study period was between 7/1/21-4/5/22. We defined the Delta period as 7/1/21-12/12/21 and the Omicron period as beginning 12/20/21. RESULTS: Our sample included 14,520 tests (2,776 [19%] positive)-7,422 (506 [7%] positive) during Delta, and 7,098 (2270 [32%] positive) during Omicron. Benchmarked against Delta, vaccine effectiveness of two vaccine doses was lower during Omicron, with no significant protection against infection. Booster doses added significant protection, although they also showed reduced effectiveness during Omicron. Compared to employees who had received two vaccine doses, three BNT162b2 doses had a relative effectiveness of 50% (95% CI 42-56%) during Omicron, relative to 78% (95% CI 63-87%) during Delta; three mRNA1273 doses had a relative effectiveness of 56% (95% CI 45-65%) during Omicron, relative to 96% (95% CI 82-99%) during Delta. Restricting the sample to symptomatic tests yielded similar results to our primary analysis. After initial waning in BNT162b2 booster protection against infection, it remained largely stable for at least 16 weeks after vaccination. DISCUSSION: Our findings provide a strong rationale for boosters among healthcare workers in the Omicron era.

SARS-CoV-2 Transmission and Prevention in the Era of the Delta Variant.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant transmits much more rapidly than prior SARS-CoV-2 viruses. The primary mode of transmission is via short range aerosols that are emitted from the respiratory tract of an index case. There is marked heterogeneity in the spread of this virus, with 10% to 20% of index cases contributing to 80% of secondary cases, while most index cases have no subsequent transmissions. Vaccination, ventilation, masking, eye protection, and rapid case identification with contact tracing and isolation can all decrease the transmission of this virus.

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.

BACKGROUND: Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? METHODS AND FINDINGS: The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. CONCLUSIONS: Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. REVIEW PROTOCOL: Open Science Framework (https://osf.io/9ewys/).

Effectiveness of contact tracing in the control of infectious diseases: a systematic review.

BACKGROUND: Contact tracing is used for multiple infectious diseases, most recently for COVID-19, but data regarding its effectiveness in disease control are scarce. To address this knowledge gap and inform public health decision making for COVID-19, we systematically reviewed the existing literature to determine the effectiveness of contact tracing in the control of communicable illness. METHODS: We searched PubMed, Embase, and the Cochrane Library from database inception up to Nov 22, 2021, for published studies evaluating associations between provider-initiated contact tracing for transmissible infectious diseases and one of three outcomes of interest: case detection rates among contacts or at the community level, overall forward transmission, or overall disease incidence. Clinical trials and observational studies were eligible, with no language or date restrictions. Reference lists of reviews were searched for additional studies. We excluded studies without a control group, using only mathematical modelling, not reporting a primary outcome of interest, or solely examining patient-initiated contact tracing. One reviewer applied eligibility criteria to each screened abstract and full-text article, and two reviewers independently extracted summary effect estimates and additional data from eligible studies. Only data reported in published manuscripts or supplemental material was extracted. Risk of bias for each included study was assessed with the Cochrane Risk of Bias 2 tool (randomised studies) or the Newcastle-Ottawa Scale (non-randomised studies). FINDINGS: We identified 9050 unique citations, of which 47 studies met the inclusion criteria: six were focused on COVID-19, 20 on tuberculosis, eight on HIV, 12 on curable sexually transmitted infections (STIs), and one on measles. More than 2 million index patients were included across a variety of settings (both urban and rural areas and low-resource and high-resource settings). Of the 47 studies, 29 (61·7%) used observational designs, including all studies on COVID-19, and 18 (38·3%) were randomised controlled trials. 40 studies compared provider-initiated contact tracing with other interventions or evaluated expansions of provider-initiated contact tracing, and seven compared programmatic adaptations within provider-initiated contact tracing. 29 (72·5%) of the 40 studies evaluating the effect of provider-initiated contact tracing, including four (66·7%) of six COVID-19 studies, found contact tracing interventions were associated with improvements in at least one outcome of interest. 23 (48·9%) studies had low risk of bias, 22 (46·8%) studies had some risk of bias, and two (4·3%) studies (both randomised controlled trials on curable STIs) had high risk of bias. INTERPRETATION: Provider-initiated contact tracing can be an effective public health tool. However, the ability of authorities to make informed choices about its deployment might be limited by heterogenous approaches to contact tracing in studies, a scarcity of quantitative evidence on its effectiveness, and absence of specificity of tracing parameters most important for disease control. FUNDING: The Sullivan Family Foundation, Massachusetts General Hospital Executive Committee on Research, and US National Institutes of Health.

Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called "superspreading events." Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.

New Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19.

Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is the prodrug of an adenosine analogue that inhibits viral replication of several RNA virus families, including Coronaviridae Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir leads to improved survival, decreased lung injury, and decreased levels of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms of faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Here, clinical trials published to date are presented and appraised. Remdesivir's potential benefits and its favorable adverse-event profile make it an option for the treatment of COVID-19. This article examines the available literature describing remdesivir's pharmacology, pharmacokinetics, and preclinical and clinical data.

Towards an accurate and systematic characterisation of persistently asymptomatic infection with SARS-CoV-2.

People with persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience no symptoms throughout the course of infection, and pre-symptomatic individuals become infectious days before they report symptoms. Transmission of SARS-CoV-2 from individuals without symptoms contributes to pandemic spread, but the extent of transmission from persistently asymptomatic individuals remains unknown. We describe three methodological issues that hinder attempts to estimate this proportion. First, incomplete symptom assessment probably overestimates the asymptomatic fraction. Second, studies with inadequate follow-up misclassify pre-symptomatic individuals. Third, serological studies might identify people with previously unrecognised infection, but reliance on poorly defined antibody responses and retrospective symptom assessment might result in misclassification. We provide recommendations regarding definitions, detection, documentation, and follow-up to improve the identification and evaluation of people with persistently asymptomatic SARS-CoV-2 infection and their contacts. Accurate characterisation of the persistently asymptomatic fraction of infected individuals might shed light on COVID-19 pathogenesis and transmission dynamics, and inform public health responses.