Unintended consequences of implementing non-pharmaceutical interventions for the COVID-19 response in Africa: experiences from DRC, Nigeria, Senegal, and Uganda.

INTRODUCTION: The coronavirus (COVID 19) pandemic is one of the most terrifying disasters of the twenty-first century. The non-pharmaceutical interventions (NPIs) implemented to control the spread of the disease had numerous positive consequences. However, there were also unintended consequences-positively or negatively related to the nature of the interventions, the target, the level and duration of implementation. This article describes the unintended economic, Psychosocial and environmental consequences of NPIs in four African countries. METHODS: We conducted a mixed-methods study in the Democratic Republic of Congo (DRC), Nigeria, Senegal and Uganda. A comprehensive conceptual framework, supported by a clear theory of change was adopted to encompass both systemic and non-systemic interventions. The data collection approaches included: (i) review of literature; (ii) analysis of secondary data for selected indicators; and (ii) key informant interviews with policy makers, civil society, local leaders, and law enforcement staff. The results were synthesized around thematic areas. RESULTS: Over the first six to nine months of the pandemic, NPIs especially lockdowns, travel restrictions, curfews, school closures, and prohibition of mass gathering resulted into both positive and negative unintended consequences cutting across economic, psychological, and environmental platforms. DRC, Nigeria, and Uganda observed reduced crime rates and road traffic accidents, while Uganda also reported reduced air pollution. In addition, hygiene practices have improved through health promotion measures that have been promoted for the response to the pandemic. All countries experienced economic slowdown, job losses heavily impacting women and poor households, increased sexual and gender-based violence, teenage pregnancies, and early marriages, increased poor mental health conditions, increased waste generation with poor disposal, among others. CONCLUSION: Despite achieving pandemic control, the stringent NPIs had several negative and few positive unintended consequences. Governments need to balance the negative and positive consequences of NPIs by anticipating and instituting measures that will support and protect vulnerable groups especially the poor, the elderly, women, and children. Noticeable efforts, including measures to avoid forced into marriage, increasing inequities, economic support to urban poor; those living with disabilities, migrant workers, and refugees, had been conducted to mitigate the negative effects of the NIPs.

Area-specific covid-19 effects on health services utilization in the Democratic Republic of the Congo using routine health information system data.

BACKGROUND: Since March 2020, the COVID-19 pandemic has shocked health systems worldwide. This analysis investigated the effects of the pandemic on basic health services utilization in the Democratic Republic of the Congo (DRC) and examined the variability of COVID effects in the capital city Kinshasa, in other urban areas, and in rural areas. METHODS: We estimated time trends models using national health information system data to replicate pre-COVID-19 (i.e., January 2017-February 2020) trajectories of health service utilization, and then used those models to estimate what the levels would have been in the absence of COVID-19 during the pandemic period, starting in March 2020 through March 2021. We classified the difference between the observed and predicted levels as the effect of COVID-19 on health services. We estimated 95% confidence intervals and p-values to examine if the effect of the pandemic, nationally and within specific geographies, was statistically significant. RESULTS: Our results indicate that COVID-19 negatively impacted health services and subsequent recovery varied by service type and by geographical area. COVID-19 had a lasting impact on overall service utilization as well as on malaria and pneumonia-related visits among young children in the DRC. We also found that the effects of COVID-19 were even more immediate and stronger in the capital city of Kinshasa compared with the national effect. Both nationally and in Kinshasa, most affected services had slow and incomplete recovery to expected levels. Therefore, our analysis indicates that COVID-19 continued to affect health services in the DRC throughout the first year of the pandemic. CONCLUSIONS: The methodology used in this article allows for examining the variability in magnitude, timing, and duration of the COVID effects within geographical areas of the DRC and nationally. This analytical procedure based on national health information system data could be applied to surveil health service disruptions and better inform rapid responses from health service managers and policymakers.

The Politics of the Second Vaccine: Debates Surrounding Ebola Vaccine Trials in Eastern Democratic Republic of the Congo

Two experimental Ebola vaccines were deployed during the tenth Ebola epidemic (2018–20) in the Democratic Republic of the Congo (DRC). The first, the Ervebo vaccine manufactured by Merck, was used as part of a ring vaccination in the epicentre of the epidemic in North Kivu. In 2019, the prime- (Ad26.ZEBOV) and boost- (MVA-BN-Filo) vaccine manufactured by Johnson & Johnson (J&J) became the second vaccine against Ebola, deployed by the DRC-EB-001 vaccine trial in Goma, North Kivu. There was international debate as to the value and ethics of testing a second vaccine in an epidemic context. This article examines how this debate unfolded among actual and potential DRC-EB-001 trial participants in Goma. Drawing on ethnographic observation, interviews and focus groups, it explores how the trial was perceived and contested on the ground and situated in broader debates about the ethics of clinical trials, especially during the COVID-19 pandemic. We illustrate how debates around the ethics of clinical research are not simply centred on bioethical principles but are inseparable from local political dynamics and broader contests about governance, inequality and exclusion.

Seroprevalence of COVID-19 infection in a densely populated district in the eastern Democratic Republic of Congo.

Data on coronavirus disease 2019 (COVID-19) prevalence in the Democratic Republic of Congo are scarce. We conducted a cross-sectional study to determine the seroprevalence of antibodies against anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the slum of Kadutu, city of Bukavu, between June and September 2021. The survey participants were all unvaccinated against SARS-CoV-2. The crude seroprevalence rate was adjusted to the known characteristics of the assay. Participants aged 15-49 years old made up 80% of the population enrolled in the study (n = 507; 319 women and 188 men). The overall crude and adjusted seroprevalence rates of antibodies for COVID-19 were 59.7% (95% CI 55.4-63.9%) and 84.0% (95% CI 76.2-92.4%), respectively. This seroprevalence rate indicates widespread dissemination of SARS-CoV-2 in these communities. COVID-19 symptoms were either absent or mild in more than half of the participants with antibodies for COVID-19 and none of the participants with antibodies for COVID-19 required hospitalisation. These results suggest that SARS-CoV-2 spread did not appear to be associated with severe symptoms in the population of these settlements and that many cases went unreported in these densely populated locations. The relevance of vaccination in these communities should be thoroughly investigated.

Using Population Mobility Patterns to Adapt COVID-19 Response Strategies in 3 East Africa Countries.

The COVID-19 pandemic spread between neighboring countries through land, water, and air travel. Since May 2020, ministries of health for the Democratic Republic of the Congo, Tanzania, and Uganda have sought to clarify population movement patterns to improve their disease surveillance and pandemic response efforts. Ministry of Health-led teams completed focus group discussions with participatory mapping using country-adapted Population Connectivity Across Borders toolkits. They analyzed the qualitative and spatial data to prioritize locations for enhanced COVID-19 surveillance, community outreach, and cross-border collaboration. Each country employed varying toolkit strategies, but all countries applied the results to adapt their national and binational communicable disease response strategies during the pandemic, although the Democratic Republic of the Congo used only the raw data rather than generating datasets and digitized products. This 3-country comparison highlights how governments create preparedness and response strategies adapted to their unique sociocultural and cross-border dynamics to strengthen global health security.

Conflict, epidemic and faith communities: church-state relations during the fight against Covid-19 in north-eastern DR Congo.

BACKGROUND: Understanding and improving access to essential services in (post)-conflict settings requires paying particular attention to the actors who occupy the space left 'empty' by weak or deficient State institutions. Religious institutions often play a fundamental role among these actors and typically benefit from high trust capital, a rare resource in so-called 'fragile' states. While there is a literature looking at the role faith organisations play to mobilise and sensitise communities during emergencies, our focus is on a different dimension: the reconfiguration of the relationship between religion and health authorities impelled by health crises. METHODS: We analyse observations, interviews, and focus group discussions with 21 leaders from eight different religious groups in Ituri province in 2020-2021. RESULTS: Faith institutions handled the Covid-19 lockdown period by using and redeploying structures at the grassroots level but also by responding to health authorities' call for support. New actors usually not associated with the health system, such as revivalist churches, became involved. The interviewed religious leaders, especially those whose congregations were not previously involved in healthcare provision, felt that they were doing a favour to the State and the health authorities by engaging in community-level awareness-raising, but also, crucially, by 'depoliticising' Covid-19 through their public commitment against Covid-19 and work with the authorities in a context where the public response to epidemics has been highly contentious in recent years (particularly during the Ebola outbreak). The closure of places of worship during the lockdown shocked all faith leaders but, ultimately, most were inclined to follow and support health authorities. Such experience was, however, often one of frustration and of feeling unheard. CONCLUSION: In the short run, depoliticization may help address health emergencies, but in the longer run and in the absence of a credible space for discussion, it may affect the constructive criticism of health system responses and health system strengthening. The faith leaders are putting forward the desire for a relationship that is not just subordination of the religious to the imperatives of health care but a dialogue that allows the experiences of the faithful in conflict zones to be brought to the fore.

The State of Pharmaceutical Manufacturing in the Democratic Republic of Congo: The Journey so Far.

Despite a population of over 89 million people, the Democratic Republic of Congo (DRC) has just 30 local pharmaceutical manufacturers (DRC) with the majority of manufacturers based in Kinshasa, the capital city. Of the total number of pharmaceutical products sold in the DRC, just 10% accounts for those manufactured locally. The DRC remains dependent on other countries such as China and India for the supply of active pharmaceutical ingredients (APIs) -thus, local pharmaceutical manufacturing is therefore reliant on imported commodities and industrial machinery. Given the relevance of the pharmaceutical industry, it is vital to pay careful attention to the problems affecting it. Here, we assess the current situation of pharmaceutical manufacturing in the DRC, examine current challenges, and provide solutions for future development.

Challenges to COVID-19 vaccine introduction in the Democratic Republic of the Congo - a commentary.

COVID-19 vaccination in the Democratic Republic of the Congo (DRC) began in April 2021. A month later, most COVID-19 vaccine doses were reallocated to other African countries, due to low vaccine uptake and the realization that the doses would expire before use. Based on data available on 13 August 2022, 2.76% of the DRC population had been fully vaccinated with last dose of primary series of COVID-19 vaccine, placing the country second to last in Africa and in the last five in global COVID-19 vaccination coverage. The DRC's reliance on vaccine donations requires continuous adaptation of the vaccine deployment plan to match incoming COVID-19 vaccines shipments. Challenges in planning vaccine deployments, vaccinating priority populations, coordinating, and implementing the communications plan, disbursing funds, and conducting supervision of vaccination activities have contributed to low COVID-19 vaccine coverage. In addition, the spread of rumors through social media and by various community and religious leaders resulted in high levels of vaccine hesitancy. A strong risk communication and community engagement plan, coupled with innovative efforts to target the highest-risk populations are critical to increase vaccine uptake during the next phase of COVID-19 vaccine introduction.

"Are You Sure It's Not the Corona Vaccine?" An Ebola Vaccine Trial During COVID-19 in DRC.

The COVID-19 pandemic began as an Ebola epidemic was unfolding in the Democratic Republic of the Congo. In this article, we examine how COVID-19 influenced experiences of an Ebola vaccine trial and attitudes towards medical research in Goma. First, critical debates about vaccine research became a forum in which to contest ineffective local governance and global inequality. Second, discussions about new COVID-19 therapeutics reignited critique of Western biomedical colonialism. Third, rumors were made powerful through everyday observations of the unexpected adaption of Ebola trial procedures in the pandemic. This illustrates the difficulties of maintaining participants' trust, when circumstances dictate protocol alterations mid-trial.

Understanding the Broader Impacts of COVID-19 on Women and Girls in the DRC through Integrated Outbreak Analytics to Reinforce Evidence for Rapid Operational Decision-Making

Whilst men and boys account for more COVID-19 cases and deaths, the secondary impacts of the outbreak on women and girls in the Democratic Republic of the Congo are cross-cutting and far-reaching. School closures put girls at increased risk of adolescent pregnancy, sexual violence and early marriage;more women working in the informal sector have lost jobs and been affected by closures of markets and borders;and frequent restrictions on sexual and reproductive healthcare have impacted access to services for women. Lessons learnt from previous health crises can help to highlight the extent of these issues. However, a lack of sex disaggregated data around COVID-19 morbidity and mortality in the DRC means that it is impossible to fully measure and understand the impact of the outbreak on women and girls or develop and implement appropriate interventions. This article presents a meta-synthesis of existing and ongoing analyses to highlight the broader impacts of COVID-19 on women and girls in the country.

Drivers of Routine and Outbreak Vaccination Uptake in the Western Democratic Republic of Congo: An Exploratory Study in Ten Health Zones.

We performed a cross-sectional survey on vaccination-related knowledge, attitudes, and practices (KAP) among randomly selected parents of <5 years-old children, elderly populations (aged ≥ 55 years), and health care workers (HCWs) in 10 health zones from 4 provinces of the Democratic Republic of Congo (DRC). Questionnaires targeted both routine (BCG, measles, polio) and outbreak-related (cholera, Ebola, COVID-19) vaccinations. In total, 2751 participants were included, 1165 parents, 1040 elderly, and 546 HCWs. In general, KAP expressed were supportive of vaccination uptake, although concerns regarding side effects and feelings of being insufficiently informed were more prevalent among parents and the elderly. Vaccine acceptance was lower for outbreak vaccinations (57%) than for routine vaccinations (90%). HCWs expressed the highest vaccine acceptance. Problems with the vaccine supply chain were reported by 20% of respondents. Despite a high level of positive KAP towards vaccination, parents and the elderly expressed a need to be better informed and had concerns regarding vaccine side-effects. A high acceptance for routine vaccinations was reported by participants, but somewhat less for outbreak vaccinations. In conclusion, HCWs in the communities could play a key role in the increased uptake of routine vaccinations and in optimizing uptake during outbreaks, provided that the supply chain is functioning well.

Ignorance and Global Health. Strategies and actors of the Covid-19 response in so-called Global South' countries

The Covid-19 pandemic provides a novel opportunity to study the production of knowledge in the face of an 'unknown but knowable' global disease, particularly in the settings favored by 'global health' interventions: the so-called developing countries. This article focuses on the responses of fifteen African and Asian countries (with particular attention to India and the DRC). These responses fall into three broad categories: denial of the existence of the virus, replication of foreign or historical measures, and 'recycling' of local experiences. We also document the specific actors and tools that contribute to the production of ignorance about Covid-19, notably the construction and mobilisation of health data and the Covid-19 "taskforces", the emergency groups that constitute the forum for disseminating knowledge and/or producing ignorance about the pandemic.

Turning mobile big data insights into public health responses in times of pandemics: Lessons learnt from the Democratic Republic of the Congo

In low-income countries like the Democratic Republic of the Congo (DRC)—where data is scarce and national statistics offices often under-resourced—aggregated and anonymised mobile operators’ data can provide vital insights for decision-makers to promptly respond to both prevailing and new pandemics, such as COVID-19. Yet, while research on possible applications of mobile big data (MBD) analytics for COVID-19 is growing, there is still little evidence on how such use cases are actually being adopted by governmental authorities and how MBD insights can effectively be turned into informed public health actions in times of crises. This four-part commentary paper aims to bridge such literature gaps, by sharing lessons learnt from the DRC, whereby Congolese public health authorities, through a steep learning curve, have initiated a public–private sector dialogue with local mobile network operators (MNOs) and their ecosystem partners to leverage population mobility insights for COVID-19 policy-making. After having set the scene on the policy relevance of MBD analytics in the context of the DRC in the first section, the paper will then detail four key enablers that contributed, since March 2020, to accelerate Congolese authorities’ uptake of MBD, thus effectively increasing preparedness for future pandemics. Thirdly, we showcase concreate use-cases where “readiness-to-use” has actually translated into actual “usage” and “adoption” for decision-making, while introducing other use cases currently under development. Finally, we explore challenges when harnessing telco big data for decision-making with the ultimate aim to share lessons to replicate the successes and steer the development of MBD for social good in other low-income countries.

High Prevalence of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (Anti-SARS-CoV-2) Antibodies After the First Wave of Coronavirus Disease 2019 (COVID-19) in Kinshasa, Democratic Republic of the Congo: Results of a Cross-sectional Household-Based Survey.

BACKGROUND: In October 2020, after the first wave of coronavirus disease 2019 (COVID-19), only 8290 confirmed cases were reported in Kinshasa, Democratic Republic of the Congo, but the real prevalence remains unknown. To guide public health policies, we aimed to describe the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies in the general population in Kinshasa. METHODS: We conducted a cross-sectional, household-based serosurvey between 22 October 2020 and 8 November 2020. Participants were interviewed at home and tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins in a Luminex-based assay. A positive serology was defined as a sample that reacted with both SARS-CoV-2 proteins (100% sensitivity, 99.7% specificity). The overall weighted, age-standardized prevalence was estimated and the infection-to-case ratio was calculated to determine the proportion of undiagnosed SARS-CoV-2 infections. RESULTS: A total of 1233 participants from 292 households were included (mean age, 32.4 years; 764 [61.2%] women). The overall weighted, age-standardized SARS-CoV-2 seroprevalence was 16.6% (95% CI: 14.0-19.5%). The estimated infection-to-case ratio was 292:1. Prevalence was higher among participants ≥40 years than among those <18 years (21.2% vs 14.9%, respectively; P < .05). It was also higher in participants who reported hospitalization than among those who did not (29.8% vs 16.0%, respectively; P < .05). However, differences were not significant in the multivariate model (P = .1). CONCLUSIONS: The prevalence of SARS-CoV-2 is much higher than the number of COVID-19 cases reported. These results justify the organization of a sequential series of serosurveys by public health authorities to adapt response measures to the dynamics of the pandemic.

Crisis responses, opportunity, and public authority during Covid-19's first wave in Uganda, the Democratic Republic of Congo, and South Sudan.

Discussions on African responses to Covid-19 have focused on the state and its international backers. Far less is known about a wider range of public authorities, including chiefs, humanitarians, criminal gangs, and armed groups. This paper investigates how the pandemic provided opportunities for claims to and contests over power in Uganda, the Democratic Republic of the Congo, and South Sudan. Ethnographic research is used to contend that local forms of public authority can be akin to miniature sovereigns, able to interpret dictates, policies, and advice as required. Alongside coping with existing complex protracted emergencies, many try to advance their own agendas and secure benefits. Those they seek to govern, though, do not passively accept the new normal, instead often challenging those in positions of influence. This paper assesses which of these actions and reactions will have lasting effects on local notions of statehood and argues for a public authorities lens in times of crisis.

A new high-content screening assay of the entire hepatitis B virus life cycle identifies novel antivirals.

BACKGROUND & AIMS: Chronic hepatitis B is an incurable disease. Addressing the unmet medical need for therapies has been hampered by a lack of suitable cell culture models to investigate the HBV life cycle in a single experimental setup. We sought to develop a platform suitable to investigate all aspects of the entire HBV life cycle. METHODS: HepG2-NTCPsec+ cells were inoculated with HBV. Supernatants of infected cells were transferred to naïve cells. Inhibition of infection was determined in primary and secondary infected cells by high-content imaging of viral and cellular factors. Novel antivirals were triaged in cells infected with cell culture- or patient-derived HBV and in stably virus replicating cells. HBV internalisation and target-based receptor binding assays were conducted. RESULTS: We developed an HBV platform, screened 2,102 drugs and bioactives, and identified 3 early and 38 late novel HBV life cycle inhibitors using infectious HBV genotype D. Two early inhibitors, pranlukast (EC50 4.3 µM; 50% cytotoxic concentration [CC50] >50 µM) and cytochalasin D (EC50 0.07 µM; CC50 >50 µM), and 2 late inhibitors, fludarabine (EC50 0.1 µM; CC50 13.4 µM) and dexmedetomidine (EC50 6.2 µM; CC50 >50 µM), were further investigated. Pranlukast inhibited HBV preS1 binding, whereas cytochalasin D prevented the internalisation of HBV. Fludarabine inhibited the secretion of HBV progeny DNA, whereas dexmedetomidine interfered with the infectivity of HBV progeny. Patient-derived HBV genotype C was efficiently inhibited by fludarabine (EC50 0.08 µM) and dexmedetomidine (EC50 8.7 µM). CONCLUSIONS: The newly developed high-content assay is suitable to screen large-scale drug libraries, enables monitoring of the entire HBV life cycle, and discriminates between inhibition of early and late viral life cycle events. LAY SUMMARY: HBV infection is an incurable, chronic disease with few available treatments. Addressing this unmet medical need has been hampered by a lack of suitable cell culture models to study the entire viral life cycle in a single experimental setup. We developed an image-based approach suitable to screen large numbers of drugs, using a cell line that can be infected by HBV and produces large amounts of virus particles. By transferring viral supernatants from these infected cells to uninfected target cells, we could monitor the entire viral life cycle. We used this system to screen drug libraries and identified novel anti-HBV inhibitors that potently inhibit HBV in various phases of its life cycle. This assay will be an important new tool to study the HBV life cycle and accelerate the development of novel therapeutic strategies.

Intimate Partners Violence against Women during a COVID-19 Lockdown Period: Results of an Online Survey in 7 Provinces of the Democratic Republic of Congo.

Intimate Partners' Violence (IPV) is a public health problem with long-lasting mental and physical health consequences for victims and their families. As evidence has been increasing that COVID-19 lockdown measures may exacerbate IPV, our study sought to describe the magnitude of IPV in women and identify associated determinants. An online survey was conducted in the Democratic Republic of Congo (DRC) from 24 August to 8 September 2020. Of the 4160 respondents, 2002 eligible women were included in the data analysis. Their mean age was 36.3 (SD: 8.2). Most women (65.8%) were younger than 40 years old. Prevalence of any form of IPV was 11.7%. Being in the 30-39 and >50 years' age groups (OR = 0.66, CI: 0.46-0.95; p = 0.026 and OR = 0.23, CI: 0.11-048; p < 0.001, respectively), living in urban setting (OR = 0.63, CI: 0.41-0.99; p = 0.047), and belonging to the middle socioeconomic class (OR = 0.48, CI: 0.29-0.79; p = 0.003) significantly decreased the odds for experiencing IPV. Lower socioeconomic status (OR = 1.84, CI: 1.04-3.24; p = 0.035) and being pregnant (OR = 1.63, CI: 1.16-2.29; p = 0.005) or uncertain of pregnancy status (OR = 2.01, CI: 1.17-3.44; p = 0.011) significantly increased the odds for reporting IPV. Additional qualitative research is needed to identify the underlying reasons and mechanisms of IPV in order to develop and implement prevention interventions.

Atypical respiratory distress in eastern Democratic Republic of the Congo prior to the COVID-19 pandemic. A case report.

BACKGROUND: Predictions have been made that Africa would be the most vulnerable continent to the novel Coronavirus disease 2019 (COVID-19). Interestingly, the spread of the disease in Africa seems to have been delayed and initially slower than in many parts of the world. Here we report on two cases of respiratory distress in our region before the official declaration of the disease in December 2019, cases which in the present times would be suspect of COVID-19. CASE PRESENTATION: These two cases (one 55-year-old man and one 25-year-old woman) of acute respiratory distress secondary to atypical pneumonia were seen in Bukavu, in Eastern Democratic Republic of the Congo (DRC), between September and December 2019. One patient had returned from China and the other had close contacts with travellers from China in the 2 weeks prior to the onset of symptoms. In either case, the aetiology could not be accurately determined. However, the two cases presented a clinical picture (progressive dyspnoea, preceded by dry cough and fever) and laboratory changes (procalcitonin within the normal range, slight inflammation, and lymphopenia) compatible with a viral infection. The chest X-ray series of the first patient showed lesions (reticulations, ground glass, and nodules ≤6 mm) similar to those currently found in COVID-19 patients. In addition, unlike the 25-year-old female patient who had no comorbidity, the 55-year-old male patient who had hypertension as comorbidity, developed a more severe acute respiratory distress which progressed to death. CONCLUSION: These cases bring to the attention the fact that COVID-19-like syndromes may have already been present in the region months before the official beginning of the pandemic. This also brings to question whether a prior presence of the disease or infections with related virus may account for the delayed and less extensive development of the pandemic in the region.

Analysis, modeling and optimal control of COVID-19 outbreak with three forms of infection in Democratic Republic of the Congo.

This paper deals with modeling and simulation of the novel coronavirus in which the infectious individuals are divided into three subgroups representing three forms of infection. The rigorous analysis of the mathematical model is provided. We provide also a rigorous derivation of the basic reproduction number R 0 . For R 0 < 1 , we prove that the Disease Free Equilibium (DFE) is Globally Asymptotically Stable (GAS), thus COVID-19 extincts; whereas for R 0 > 1 , we found the co-existing phenomena under some assumptions and parametric values. Elasticity indices for R 0 with respect to different parameters are calculated with baseline parameter values estimated. We also prove that a transcritical bifurcation occurs at R 0 = 1 . Taking into account the control strategies like screening, treatment and isolation (social distancing measures), we present the optimal control problem of minimizing the cost due to the application of these measures. By reducing the values of some parameters, such as death rates (representing a management effort for all categories of people) and recovered rates (representing the action of reduction in transmission, improved screening, treatment for individuals diagnosed positive to COVID-19 and the implementation of barrier measures limiting contamination for undiagnosed individuals), it appears that after 140 - 170 days, the peak of the pandemic is reached and shows that by continuing with this strategy, COVID-19 could be eliminated in the population.

The potential of BEN815 as an anti-inflammatory, antiviral and antioxidant agent for the treatment of COVID-19.

Background: The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective antiviral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough, it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal. Purpose: Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves (Psidium guajava), green tea leaves (Camellia sinensis), and rose petals (Rosa hybrida), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19. Study design: We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells. Methods: The principal active ingredients in BEN815 were determined and quantified using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining. Results: BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major constituents of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells. Conclusion: BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19.