Estimating the potential need and impact of SARS-CoV-2 test-and-treat programs with oral antivirals in low-and-middle-income countries

Oral antivirals can potentially reduce the burden of COVID-19. However, low SARS-CoV-2 clinical testing rates in many low- and middle-income countries (LMICs) (mean <10 tests/100,000 people/day, July 2022) makes the development of effective test- and-treat programs challenging. Here, we used an agent-based model to investigate how testing rates and strategies could affect development of test- and-treat programs in three representative LMICs. We find that at <10 tests/100,000 people/day, test- and-treat programs are unlikely to have any impact on the public health burden of COVID-19. At low effective transmission rates (Rt [≤] 1.2), increasing to 100 tests/100,000 people/day and allowing uncapped distribution of antivirals to LMICs (estimate = 26,000,000-90,000,000 courses/year for all LMICs), could avert up to 65% of severe cases, particularly in countries with older populations. For higher Rt, significant reductions in severe cases are only possible by substantially increasing testing rates or restricting clinical testing to those with higher risk of severe disease.

Strategies for using antigen rapid diagnostic tests to reduce transmission of SARS-CoV-2 in low- and middle-income countries: a mathematical modelling study

BackgroundIncreasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries; high-income countries=600 tests/100,000 people/day; LMICs=14 tests/ 100,000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. MethodsWe used PATAT, an LMIC-focused agent-based model to simulate COVID-19 epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from non-SARS-CoV-2 infected individuals and measured impact based on the number of infections averted due to test-and-isolate. ResultsTesting symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200-400 tests/100,000 people/day on average as symptomatic testing demand is highly influenced by non-SARS-CoV-2 infected individuals. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yields the largest additional infections averted. ConclusionsTesting strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.

Low testing rates limit the ability of genomic surveillance programs to monitor SARS-CoV-2 variants: a mathematical modelling study

The first step in SARS-CoV-2 genomic surveillance is testing to identify infected people. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (LMICs) (mean = 27 tests/100,000 people/day). We simulated COVID-19 epidemics in a prototypical LMIC to investigate how testing rates, sampling strategies, and sequencing proportions jointly impact surveillance outcomes and showed that low testing rates and spatiotemporal biases delay time-to-detection of new variants by weeks-to-months and can lead to unreliable estimates of variant prevalence even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of [~]100 tests/100,000 people/day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.

Impacts of the COVID-19 pandemic on future seasonal influenza epidemic

BackgroundDuring the first two years of the COVID-19 pandemic, the circulation of seasonal influenza viruses was unprecedentedly low. This led to concerns that the lack of immune stimulation to influenza viruses combined with waning antibody titres could lead to increased susceptibility to influenza in subsequent seasons, resulting in larger and more severe epidemics. MethodsWe analyzed historical influenza virus epidemiological data from 2003-2019 to assess the historical frequency of near-absence of seasonal influenza virus circulation and its impact on the size and severity of subsequent epidemics. Additionally, we measured haemagglutination inhibition-based antibody titres against seasonal influenza viruses using longitudinal serum samples from 165 healthy adults, collected before and during the COVID-19 pandemic, and estimated how antibody titres against seasonal influenza waned during the first two years of the pandemic. FindingsLow country-level prevalence of influenza virus (sub)types over one or more years occurred frequently before the COVID-19 pandemic and had relatively small impacts on subsequent epidemic size and severity. Additionally, antibody titres against seasonal influenza viruses waned negligibly during the first two years of the pandemic. InterpretationThe commonly held notion that lulls in influenza virus circulation, as observed during the COVID-19 pandemic, will lead to larger and/or more severe subsequent epidemics might not be fully warranted, and it is likely that post-lull seasons will be similar in size and severity to pre-lull seasons. FundingEuropean Research Council, Netherlands Organization for Scientific Research, Royal Dutch Academy of Sciences, Public Health Service of Amsterdam. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSDuring the first years of the COVID-19 pandemic, the incidence of seasonal influenza was unusually low, leading to widespread concerns of exceptionally large and/or severe influenza epidemics in the coming years. We searched PubMed and Google Scholar using a combination of search terms (i.e., "seasonal influenza", "SARS-CoV-2", "COVID-19", "low incidence", "waning rates", "immune protection") and critically considered published articles and preprints that studied or reviewed the low incidence of seasonal influenza viruses since the start of the COVID-19 pandemic and its potential impact on future seasonal influenza epidemics. We found a substantial body of work describing how influenza virus circulation was reduced during the COVID-19 pandemic, and a number of studies projecting the size of future epidemics, each positing that post-pandemic epidemics are likely to be larger than those observed pre-pandemic. However, it remains unclear to what extent the assumed relationship between accumulated susceptibility and subsequent epidemic size holds, and it remains unknown to what extent antibody levels have waned during the COVID-19 pandemic. Both are potentially crucial for accurate prediction of post-pandemic epidemic sizes. Added value of this studyWe find that the relationship between epidemic size and severity and the magnitude of circulation in the preceding season(s) is decidedly more complex than assumed, with the magnitude of influenza circulation in preceding seasons having only limited effects on subsequent epidemic size and severity. Rather, epidemic size and severity are dominated by season-specific effects unrelated to the magnitude of circulation in the preceding season(s). Similarly, we find that antibody levels waned only modestly during the COVID-19 pandemic. Implications of all the available evidenceThe lack of changes observed in the patterns of measured antibody titres against seasonal influenza viruses in adults and nearly two decades of epidemiological data suggest that post-pandemic epidemic sizes will likely be similar to those observed pre-pandemic, and challenge the commonly held notion that the widespread concern that the near-absence of seasonal influenza virus circulation during the COVID-19 pandemic, or potential future lulls, are likely to result in larger influenza epidemics in subsequent years.

Mapping the antigenic diversification of SARS-CoV-2

Large-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similar to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants-of-concern (VOCs) of a unique set of sera from patients infected with a range of VOCs. Infections with D614G or Alpha strains induced the broadest immunity, while individuals infected with other VOCs had more strain-specific responses. Omicron BA.1 and BA.2 were substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that Omicron BA.1 and BA.2 are antigenically most distinct from D614G, associated with immune escape and likely requiring vaccine updates to ensure vaccine effectiveness.

Optimal use of COVID19 Ag-RDT screening at border crossings to prevent community transmission: a modeling analysis

BackgroundCountries around the world have implemented restrictions on mobility, especially cross-border travel to reduce or prevent SARS-CoV-2 community transmission. Rapid antigen testing (Ag-RDT), with on-site administration and rapid turnaround time may provide a valuable screening measure to ease cross-border travel while minimizing risk of local transmission. To maximize impact, we developed an optimal Ag-RDT screening algorithm for cross-border entry. MethodsUsing a previously developed mathematical model, we determined the daily number of imported COVID-19 cases that would generate no more than a relative 1% increase in cases over one month for different effective reproductive numbers (Rt) of the recipient country. We then developed an algorithm- for differing levels of Rt, arrivals per day, mode of travel, and SARS-CoV-2 prevalence amongst travelers-to determine the minimum proportion of people that would need Ag-RDT testing at border crossings to ensure no greater than the relative 1% community spread increase. FindingsWhen daily international arrivals and/or COVID-19 prevalence amongst arrivals increases, the proportion of arrivals required to test using Ag-RDT increases. At very high numbers of international arrivals/COVID-19 prevalence, Ag-RDT testing is not sufficient to prevent increased community spread, especially for lower levels of Rt. In these cases, Ag-RDT screening would need to be supplemented with other measures to prevent an increase in community transmission. InterpretationAn efficient Ag-RDT algorithm for SARS-CoV-2 testing depends strongly on Rt, volume of travel, proportion of land and air arrivals, test sensitivity, and COVID-19 prevalence among travelers. FundingUSAID, Government of the Netherlands

Changes in HIV Treatment Differentiated Care Utilization During the COVID-19 Pandemic in Zambia

BackgroundDifferentiated service delivery (DSD) models aim to lessen the burden of HIV treatment on patients and providers in part by reducing requirements for facility visits and extending dispensing intervals. With the advent of the COVID-19 pandemic, minimizing patient contact with healthcare facilities and other patients, while maintaining treatment continuity and avoiding loss to care, has become more urgent, resulting in efforts to increase DSD uptake. We assessed the extent to which DSD coverage and antiretroviral treatment (ART) dispensing intervals have changed during the COVID-19 pandemic in Zambia. MethodsWe used patient data from Zambias electronic medical record system (SmartCare) for 737 health facilities, representing about 3/4 of all ART patients nationally, to compare the numbers and proportional distributions of patients enrolled in DSD models in the six months before and six months after the first case of COVID-19 was diagnosed in Zambia in March 2020. Segmented linear regression was used to determine whether the introduction of COVID-19 into Zambia further accelerated the increase in DSD scale-up. ResultsBetween September 2019 and August 2020, 181,317 patients aged 15+ (81,520 and 99,797 from September 1, 2019 to March 1, 2020 and from March 1 to August 31, 2020, respectively) enrolled in DSD models in Zambia. Overall participation in all DSD models increased over the study period, but uptake varied by model. The rate of acceleration increased in the second period for home ART delivery (152%), [≤]2-month fast-track (143%), and 3-month MMD (139%). There were significant decelerations in the increase in enrolment for 4-6-month fast-track (-28%) and other models (-19%). ConclusionsParticipation in DSD models for stable ART patients in Zambia increased after the advent of COVID-19, but dispensing intervals diminished. Eliminating obstacles to longer dispensing intervals, including those related to supply chain management, should be prioritized to achieve the expected benefits of DSD models and minimize COVID-19 risk.

Nowcasting and forecasting provincial-level SARS-CoV-2 case positivity using google search data in South Africa

Data from non-traditional data sources, such as social media, search engines, and remote sensing, have previously demonstrated utility for disease surveillance. Few studies, however, have focused on countries in Africa, particularly during the SARS-CoV-2 pandemic. In this study, we use searches of COVID-19 symptoms, questions, and at-home remedies submitted to Google to model COVID-19 in South Africa, and assess how well the Google search data forecast short-term COVID-19 trends. Our findings suggest that information seeking trends on COVID-19 could guide models for anticipating COVID-19 trends and coordinating appropriate response measures.

Serological testing in addition to PCR screening for the re-opening of American colleges and universities: potential for cost-savings without compromising pandemic mitigation

ImportanceThe addition of a serological testing could reduce the overall testing costs of a PCR-based SARS-CoV-2 testing reopening plan for colleges/universities in the United States, without compromising the efficacy of the testing plan. ObjectivesTo determine whether a college/university reopening SARS-CoV-2 testing plan that includes serological testing can be cost-saving compared to a PCR-only testing. Design, Setting, and ParticipantsWe assessed costs of serological testing in addition to PCR testing under various scenarios of university sizes (2000, 10,000, and 40,000) and epidemic conditions (initial antibody prevalence 2.5-15%; cumulative SARS-CoV-2 incidence during the school year 5-30%) of SARS-CoV-2 in the United States. We estimated total testing costs and relative percentage of cost-savings of different screening (i.e. targeted/ universal) and testing (i.e. in-sourcing/out-sourcing) scenarios between September 2020-May 2021. Main Outcomes and MeasuresTesting costs of serological testing and PCR testing, Relative percentage of cost saving by including serology testing in addition to PCR testing. ResultsIncluding baseline serology testing alongside routine regular PCR testing can reduce total test volumes and related costs throughout the school year. While the total testing cost is likely much lower if regular PCR testing is insourced compared to outsourced ($5 million vs $34 million for university size 10,000), including serologic testing could achieve the up to 20% cost-savings relative to PCR testing alone. The insourcing of serological testing when PCR testing is insourced can achieve greater cost-savings under high initial antibody prevalence (>5%) and cumulative incidence throughout the school year (>10%) at medium and large sized universities. If PCR testing is outsourced, however, the inclusion of serological testing becomes always preferred in most university sizes and epidemic conditions. Conclusions and RelevanceWhile regular PCR testing alone is the preferred strategy for containing epidemics, including serology testing may help achieve cost-savings if outbreaks are anticipated, or if baseline seropositivity is high. Key Points (96/100)O_ST_ABSQuestionC_ST_ABSCan the addition of a serological testing reduce the overall testing costs of a PCR-based SARS-CoV-2 testing reopening plan for universities in the United States? FindingsThis costing study suggested that inclusion of serological testing in addition to outsourced PCR testing as part of a university re-opening strategy could achieve cost savings of up to 20%. The amount of savings, or additional costs, is dependent on insourcing or outsourcing of testing, epidemic conditions and university size. MeaningThe relative cost-savings depend strongly on whether PCR and/or serology are being insourced or outsourced, university sizes and cumulative incidence.

Cost-effectiveness of remdesivir and dexamethasone for COVID-19 treatment in South Africa

BackgroundSouth Africa recently experienced a first peak in COVID-19 cases and mortality. Dexamethasone and remdesivir both have the potential to reduce COVID-related mortality, but their cost-effectiveness in a resource-limited setting with scant intensive care resources is unknown. MethodsWe projected intensive care unit (ICU) needs and capacity from August 2020 to January 2021 using the South African National COVID-19 Epi Model. We assessed cost-effectiveness of 1) administration of dexamethasone to ventilated patients and remdesivir to non-ventilated patients, 2) dexamethasone alone to both non-ventilated and ventilated patients, 3) remdesivir to non-ventilated patients only, and 4) dexamethasone to ventilated patients only; all relative to a scenario of standard care. We estimated costs from the healthcare system perspective in 2020 USD, deaths averted, and the incremental cost effectiveness ratios of each scenario. ResultsRemdesivir for non-ventilated patients and dexamethasone for ventilated patients was estimated to result in 1,111 deaths averted (assuming a 0-30% efficacy of remdesivir) compared to standard care, and save $11.5 million. The result was driven by the efficacy of the drugs, and the reduction of ICU-time required for patients treated with remdesivir. The scenario of dexamethasone alone to ventilated and non-ventilated patients requires additional $159,000 and averts 1,146 deaths, resulting in $139 per death averted, relative to standard care. ConclusionsThe use of dexamethasone for ventilated and remdesivir for non-ventilated patients is likely to be cost-saving compared to standard care. Given the economic and health benefits of both drugs, efforts to ensure access to these medications is paramount. 40-word summary of articles main pointThe use of remdesivir and dexamethasone for treatment of severe COVID-19 in South Africa is likely to be cost-saving relative to standard care. Enabling access to these medications should be prioritize to improve patient outcomes and reduce total costs.

Population density and basic reproductive number of COVID-19 across United States counties

The basic reproductive number (R0) is a function of contact rates among individuals, transmission probability, and duration of infectiousness. We sought to determine the association between population density and R0 of SARS-CoV-2 across U.S. counties, and whether population density could be used as a proxy for contact rates. We conducted a cross-sectional analysis using linear mixed models with random intercept and fixed slopes to assess the association of population density and R0. We also assessed whether this association was differential across county-level main mode of transportation-to-work percentage. Counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density. The effect of population density and R0 was not modified by private transportation use. Differential R0 by population density can assist in more accurate predictions of the rate of spread of SARS-CoV-2 in areas that do not yet have active cases. Article Summary LineU.S. counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density.

The role of remdesivir in South Africa: preventing COVID-19 deaths through increasing ICU capacity

Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of COVID-19 patients requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.