{'fraction_non_alphanumeric': 0.027133730529035963, 'fraction_numerical': 0.01758667719474553, 'mean_word_length': 5.002585092632486, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 6, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
A call for strengthened evidence on targeted, non-pharmaceutical interventions against COVID-19 for the protection of vulnerable individuals in sub-Saharan Africa


 Since many sub-Saharan African countries started easing their lockdown measures, COVID-19 cases have been on the rise. As COVID- 19 transmission may be difficult to stop in these settings, we propose to complement the existing COVID-19 prevention strategies aiming at reducing overall transmission with more targeted strategies to protect people at risk for severe COVID-19 disease. We suggest investigating the feasibility, acceptability, and efficacy of distributing COVID-19 prevention kits to households with persons at increased risk for severe COVID-19 disease.



Introduction
A curious imbalance exists between the research and development (R&D) efforts dedicated to pharmaceutical versus non-pharmaceutical interventions in outbreak control. The scientific output as well as the associated R&D investments for pharmaceutical interventions are often a factor higher than those for non-pharmaceutical interventions, even though the latter commonly represent a cornerstone of outbreak control. This seems no different in the case of the coronavirus disease-2019 J o u r n a l P r e -p r o o f  pandemic: at the time of writing, a PubMed search indicates that the number of published peer-reviewed articles on COVID-19 and treatment/vaccination is approximately double that of COVID-19 and containment/prevention. Pharmaceutical interventions such as treatment or vaccination benefit -rightly -from calls for innovation, extensive investigations, rigorous monitoring and evaluation, and the best that evidence-based medicine has to offer. In contrast, while nonpharmaceutical interventions such as physical distancing, lockdowns, contact tracing, facemask promotion, and others have been implemented almost ubiquitously as a measure to stem COVID-19 transmission, they have tended to be implemented as a blanket approach, with limited monitoring and evaluation, and limited generation of evidence to adapt strategies as they go along. Here, we call for the generation and strengthening of evidence to guide non-pharmaceutical interventions for COVID-19, which we illustrate with a practical proposal for assessing the impact of targeted protection of at-risk individuals in settings in sub-Saharan Africa.

COVID-19 in sub-Saharan Africa
The sub-Saharan Africa region was touched relatively late by COVID-19, with the first case occurring in Nigeria in late February 2020 (Nigeria Centre for Disease Control 2020). While implementation of general preventive measures in sub-Saharan Africa may have slowed down the pandemic, it seems it cannot be stopped: by August 14 th , there were more than one million COVID-19 cases in Africa, with more than 24,000 deaths (Africa CDC 2020). As COVID-19 diagnostic capacity remains limited in the region, the reported numbers of COVID-19 cases and deaths are likely an underestimation of the true disease burden. Moreover, since many African countries are now easing lockdown measures, the number of COVID-19 cases is likely to increase rapidly. A sharp increase has already been observed in South Africa, which now accounts for more than 50% of the continent's total confirmed cases (WHO 2020).
Despite the increasing community spread of COVID-19 in sub-Saharan Africa, mortality rates reportedly remain low in most countries. This may be related to the relatively younger demographic J o u r n a l P r e -p r o o f in the region: the proportion of persons age 60 and over was estimated to be 4.7% in 2005 and is expected to rise to 5.5% in 2030 (Velkoff and Kowal 2006), compared to approximately 20% in e.g.
Western Europe currently. Nevertheless, the region is home to more than 50 million elderly (aged 60 and over) (United Nations 2019), who can be considered at elevated risk for severe  infection. Additionally, the continent has seen a steady increase in non-communicable diseases (NCD) such as diabetes (Ojuka and Goyaram 2014) and hypertension (Bigna, Noubiap et al. 2017), which have been linked to COVID-19 severity (Rastad, Karim et al. 2020, Zhou, Chi et al. 2020, and additionally carries a high burden of infectious diseases such as HIV and tuberculosis, which have been speculated to represent particular risk factors for severe COVID-19 infection as well (Davies 2020).
With COVID-19 gaining ground in sub-Saharan Africa and the sizeable population of vulnerable individuals at risk of severe COVID-19, the often already-fragile health systems in many African settings risk being dramatically outpaced by the pandemic.

Lockdowns for COVID-19 prevention
At the onset of the COVID-19 pandemic, lockdowns were swiftly recommended as strategy for COVID-19 prevention. Such interventions were typically modelled on the COVID-19 outbreaks in high-income countries and were subsequently replicated in other settings, such as sub-Saharan Africa (Hodgins and Saad 2020). Concerns have however been raised that the pandemic follows very different trajectories in different contexts, and that a "one size fits all" approach for nonpharmaceutical interventions may not be appropriate, as the risk-benefit balance of such interventions may vary across settings (Hodgins andSaad 2020, Van Damme, Dahake et al. 2020).
Although the early implementation of lockdown measures for COVID-19 control may have contributed to the (initially) low mortality observed in most sub-Saharan Africa countries, the collateral damage resulting from this strategy is becoming increasingly apparent. Lockdown measures have resulted in major economic losses, loss of jobs (Yaya, Otu et al. 2020), increase of poverty (Yaya, Otu et al. 2020), food shortages (McLinden, Stover et al. 2020), mental health problems (Guessoum, Lachal et al. 2020, Joska, Andersen et al. 2020, domestic and other forms of violence (Joska, Andersen et al. 2020), and disruption of health services through drug shortages and an overall negative impact on the quality of non-COVID-19 healthcare. Moreover, it is expected that post-lockdown, there will be an increased burden of malaria, tuberculosis (Nghochuzie, Olwal et al. 2020) and of neglected tropical diseases resulting from the suspension of control programs. In addition to the fact that lockdown measures are more detrimental to those with the least resources, they are unlikely to be sustainable for the stretch of time required to fully curtail COVID-19 transmission in the long run.
We therefore propose to complement the extant containment measures in sub-Saharan Africa with more targeted protection strategies, aiming at protecting people at risk of severe COVID-19 disease.

A targeted strategy to protect people at risk for severe COVID-19 disease
A targeted strategy may be more efficient to decrease COVID-19 related mortality and to prevent health systems from being overwhelmed by cases in need of resource-demanding intensive support.
If implemented together with the general measures to limit the spread of COVID-19 in the population such as physical distancing, universal facemask use and frequent handwashing, such a strategy may provide authorities with the means to selectively relax population-wide measures in favour of these more targeted approaches.
Protecting persons at risk of severe COVID-19 disease may however be challenging. In high-income countries, where inter-generational mixing within households is less common and where many elderly reside specifically in long-term care facilities, protection was ostensibly straightforwardhowever, few countries failed to safeguard these populations (Ecdc Public Health Emergency Team, Danis et al. 2020, Miller 2020. In sub-Saharan Africa, where elderly family members generally live together with the rest of the family or in close contact with them, this challenge may be further compounded. Additionally, one's NCD status may be less well documented in African contexts, J o u r n a l P r e -p r o o f prohibiting self-identification as vulnerable. We propose to develop and test different targeted COVID-19 prevention strategies adapted to the sub-Saharan African context. One strategy could be to distribute COVID-19 prevention kits to households with persons at increased risk for severe COVID-19 disease.

COVID-19 prevention kits
Hygiene kits or prevention kits have been used successfully in other outbreaks, commonly for fecoorally transmitted diseases such as cholera or Ebola, as stopgap measure when population-wide prevention tools. We surmise that basic kit items will include fabric facemasks, soap, water storage capacity, alcohol-based hand gel, and health education materials. These materials should ideally cover topics such as respecting at least 1.5 m distance from the person at risk for severe COVID-19 disease, always wearing a facemask when interacting with these persons, having these persons wear a facemask when in the company of others, and limiting human interactions with these persons until COVID-19 is eliminated. Moreover families could be given access to a phone help-line for more personal advice and support.
Different ways to identify families with persons at risk for severe disease should be explored.
Identification could be integrated within a contact tracing programme, whereby a symptomatic person suspected to have COVID-19 is investigated as to whether there is a person at risk for severe COVID-19 disease in her/his household. This approach may be logistically easier to implement, as it J o u r n a l P r e -p r o o f would allow centralised distribution of kits, but risks coming too late as the person at risk could already be infected. In communities where there is high ongoing COVID-19 transmission, it may be preferable but more costly to offer prevention kits to all those with a household member at risk, irrespective of any suspicion of active COVID-19 in the family, since it is becoming increasingly clear that asymptomatic infected subjects can also spread the infection. Such an approach could be aided by demographic records that indicate the ages of residents in the different households and/or medical records from local NCD programmes, and safe and efficient distribution models to realise this approach would need to be tried and tested. Another entry point for the distribution of kits could be clinics attended by persons with co-morbidities such as diabetes, hypertension, HIV and tuberculosis. In rural areas, community health workers could play a key role in identifying vulnerable persons, health education and distribution of kits.
Who should be the focus of the targeted intervention needs to be investigated in each setting taking into account the phase of the COVID-19 epidemic, the commonness and types of vulnerable people, whether they are known in the community, the ability of the local community health workers to recognise vulnerable people, the cultural context, and the financial resources. The easiest way is to consider all persons older than 60 years at risk for severe COVID-19 disease. Recently, a frailty scale was shown to be more predictive of COVID-19 disease outcome than age and co-morbidities (Hewitt, Carter et al. 2020). However, it needs to be investigated whether community health workers will be able to categorize persons using such a scale and how much resources (time, finances) this will require.
Formative research will be necessary to explore the composition of the prevention kit; this will depend on local needs and resources. The distribution of the kits will need to be pilot-tested for feasibility and acceptability. To minimize cost, we recommend large scale local production of fabric face masks. An important component of the intervention would be the counselling of the families by the community health workers. While the exact cost for the production and dissemination of the J o u r n a l P r e -p r o o f prevention kits (including the incentives for the community health workers) may be difficult to evaluate, the proposed targeted approach appears to be more cost-beneficial than all-inclusive strategies such as providing face masks to the entire population and enforcing strict contingency measures, with the associated economic backlash.
This model of targeted intervention should be compared with interventions focusing mainly on decreasing overall COVID-19 transmission. There is thus an urgent need to upscale research capacity, in order to appropriately address these questions.

Conclusion
Currently, a large proportion of the COVID-19 research funding for the prevention COVID-19 transmission is being directed towards the development of a vaccine. It is however unlikely that an effective vaccine will be available very soon in all COVID-19 transmission foci in sub-Saharan Africa.
Therefore we recommend that well-designed studies, including randomised trials, be planned and conducted in sub-Saharan Africa to identify the most cost-efficient ways to decrease the COVID-19 disease burden, while at the same time mitigating collateral damage of prevention measures.
Hygiene kits may be one such measure worthy of investigation.
In collaboration with Somalian investigators, we have submitted a research proposal for a cluster randomised trial among camps for internally displaced persons in Somalia to compare a targeted COVID-19 prevention programme to reduce severe COVID-19 related disease and mortality with a standard COVID-19 prevention program to reduce overall COVID-19 transmission. For the moment, such a targeted intervention using prevention kits in is only possible in Somalia with external funding. However, we hope that if a significant difference in severe disease and mortality is shown, governments, non-governmental organisations and funding agencies will try to scale up and sustain similar interventions in other settings.

Conflict of interest
J o u r n a l P r e -p r o o f