key: cord-0810192-e5p43y3r
authors: Otitoloju, Adebayo A; Okafor, Ifeoma P; Fasona, Mayowa; Bawa-Allah, Kafilat Adebola; Isanbor, Chukwuemeka; Onyeka, Chukwudozie Solomon; Folarin, Olawale S; Adubi, Taiwo O; Sogbanmu, Temitope O; Ogbeibu, Anthony E
title: COVID-19 pandemic: examining the faces of spatial differences in the morbidity and mortality in sub-Saharan Africa, Europe and USA.
date: 2020-04-24
journal: nan
DOI: 10.1101/2020.04.20.20072322
sha: e6783cdb8fe050c1e67afc535f5d1d073781f9b7
doc_id: 810192
cord_uid: e5p43y3r

Background: COVID-19, the disease associated with the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently a global pandemic with several thousands of confirmed cases of infection and death. However, the death rate across affected countries shows variation deserving of critical evaluation. Methods: In this study, we evaluated differentials in COVID-19 confirmed cases of infection and associated deaths of selected countries in Sub-Sahara Africa (Nigeria and Ghana), South Africa, Europe (Italy, Spain, Sweden and UK) and USA. Data acquired for various standard databases on mutational shift of the SARS-CoV-2 virus based on geographical location, BCG vaccination policy, malaria endemicity, climatic conditions (temperature), differential healthcare approaches were evaluated over a period of 45 days from the date of reporting the index case. Results: The number of confirmed cases of infection and associated deaths in Sub-Sahara Africa were found to be very low compared to the very high values in Europe and USA over the same period. Recovery rate from COVID-19 is not correlated with the mutational attributes of the virus with the sequenced strain from Nigeria having no significant difference (p>0.05) from other geographical regions. Significantly higher (p<0.05) infection rate and mortality from COVID-19 were observed in countries (Europe and USA) without a current universal BCG vaccination policy compared to those with one (Sub-Sahara African countries). Countries with high malaria burden had significantly lower (p<0.05) cases of COVID-19 than those with low malaria burden. A strong negative correlation (-0.595) between mean annual temperature and COVID-19 infection and death was observed with 14.8% variances between temperature and COVID-19 occurrence among the countries. A clear distinction was observed in the COVID-19 disease management between the developed countries (Europe and USA) and Sub-Sahara Africa. Conclusions: The study established that the wide variation in the outcome of the COVID-19 disease burden in the selected countries are attributable largely to climatic condition (temperature) and differential healthcare approaches to management of the disease. We recommend consideration and mainstreaming of these findings for urgent intervention and management of COVID-19 across these continents.

Coronavirus disease 2019 is the disease associated with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Characterising COVID-19 as a pandemic is an acknowledgement that the coronavirus disease 2019 (COVID- 19) outbreak, which started in the Hubei province of China in 2019, has now spread to all continents, affecting most countries around the world including African countries (Cucinotta and Vanelli, 2020). Since the outbreak of COVID-19, it has spread through different countries and continents, but with differential impacts and peculiarities. The European region has recorded about 1.05 million confirmed cases and 93,000 deaths; Regions of Americas -743,000

confirmed cases and 33,000 deaths; Western Pacific Region -127,000 confirmed cases and 5558 deaths; Eastern Mediterranean Region -115,000 confirmed cases and 5,600 deaths;

South-east Asia region -23,000 confirmed cases and 1000 deaths; and Africa 12,000

confirmed cases and 500 deaths (WHO, 2020).

It has been anticipated that the impacts of Covid-19 outbreak in African countries and many developing countries would be very devastating because of several reasons including poor state of health infrastructure, poverty concerns, unfavourable living conditions in the cities, population densities and prevalence of underlying disease conditions like lower respiratory infection, malaria, diarrheal, HIV/AIDS and tuberculosis (The World Bank, 2020). In addition, many West African countries have poorly resourced health systems, rendering them unable to quickly scale up responses to disease outbreaks (Baker, 2020) . Most countries in the region have fewer than five hospital beds per 10,000 of the population and fewer than two medical doctors per 10,000 of the population. In contrast to Italy and Spain with 34 and 35 hospital beds respectively per 10,000 of the population and about 41 medical doctors per 10,000 of the population (Martinez-Alvarez, 2020). According to UNECA (2020), Africa could see 300,000 deaths from the coronavirus this year even under the best-case scenario.

Under the worst-case scenario with no interventions against the virus, Africa could see 3.3 million deaths and 1.2 billion infections. The fears being expressed by many of these genuine observers of potential dangers that may occur in Africa as a result of the COVID-19 epidemic are therefore well-founded because all the metrics point to a very catastrophic outcome as it is currently being recorded in some countries in Latin America with similar level of development and poor healthcare system (AFP News Agencywww.aljazeera.com).

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020 Despite all the concerns of poor healthcare systems and underlying poor conditions, the outbreak of COVID-19 in some parts of Africa has not resulted in the largely anticipated huge spike in the number of confirmed cases and deaths. This surprisingly low number after a thirty (30) to forty-five (45) day period of the COVID-19 outbreak in some of the African countries is raising a lot of research questions in order to understand the true situation of the epidemic in these countries and also provide lessons learnt or to be learnt around the world (Ebenso and Otu, 2020; Vaughan, 2020) .

It is therefore pertinent to investigate the trend in the spread of this disease, establish similarities or disparities among countries and attempt to determine the underlying reasons for the observed variations. Furthermore, there is an urgent demand to ensure that adequate preventive measures are put in place to ensure that the disease does not spread among very vulnerable populations where the healthcare system is at best weak and may not be capable of coping with the epidemic, unlike the more robust healthcare systems in Europe and America (Gilbert et. al., 2020) .

The main objectives of this paper are to compare COVID-19 confirmed cases and deaths data in some countries in Africa (Nigeria, Ghana and South Africa) with those reported in the more developed countries (Italy, Spain, UK, Sweden and USA) with better healthcare systems. There is therefore the need to evaluate several underlying factors in the spatial differences observed with incidence and disease burden of COVID-19. Specific factors examined in this paper are: mutational shift of the SARS-CoV-2 virus based on geographical location, BCG vaccination policy of the countries, malaria endemicity, climatic conditions (temperature), differential healthcare approaches as dictated by cultural norms, practice and unfettered access to prescription drugs.

The geographical location and basic climatic conditions of the eight study countries are as follow:

i. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 24, 2020. Mean Temperature data for 50 years (1962 to 2012) for all the study countries was sourced from the archive of the Stat World (https://stat.world/biportal/?allsol=1). The temperature data were summarized for long-term spatial and temporal means.

Information on healthcare approaches were obtained from anecdotal data, reviews of literature and statistic websites like www.nairametrics.com and www.healthdata.org. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 24, 2020. These data were analysed for significant relationships between time, confirmed cases of infection and deaths using simple linear correlation and regression models with the purpose of developing predictive equations to establish future trend and projection in each country.

Multivariate statistics using similarity indices and hierarchical cluster analysis were performed to identify similarities or disparities among countries in terms of the chosen parameters -confirmed cases and reported deaths (Hammer et al., 2001; Ogbeibu, 2014) .

Mann-Whitney test and Spearman's rank correlation were done to determine relationship between BCG vaccination, malaria endemicity and climatic condition (temperature) with level of occurrence of COVID-19 confirmed cases and deaths in study countries. Level of significance is set at 5% (p<0.05).

The SARS-CoV-2 sequences from different geographical locations were properly edited using a bio-edit tool software, as gaps within the sequence were deleted. A sequence alignment analysis was conducted using the Clustal W, which is a multiple sequence alignment program that uses seeded guide trees and HMM profile-profile techniques to generate alignments between three or more sequences, then utilizing the UPGMA/Neighbor-joining method to generate a distance matrix. The program also uses the BLOSUM scoring matrix, as default settings of gap penalty at 5, gap open penalty at 15 and finally, gap penalty cost at 6.66 per element.

An automated tree was generated after the consistent alignments. The tree was rendered using the RaxML bootstrap (Stamatakis, 2006 ). The resulting clustering shows the relationships between the countries.

The results of the daily trend of confirmed cases of infections and deaths over a 45 day period for Nigeria, Ghana, South Africa, Italy, Spain, UK, USA and Sweden are presented in . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 24, 2020. (Fig. 1) . For the recorded number of deaths from COVID-19, Italy has the highest number of deaths from the disease followed by Spain, USA, UK, Sweden, Ghana and Nigeria (least) over the 45 days period (Fig. 2) . 

In order to understand and monitor the daily trend in cases of infection and death, using available data, regression and correlation analysis were performed to establish relationships and generate predictive regression equations for each country. The higher the coefficient of determination R 2 , the higher the proportion of confirmed cases of infection and deaths accounted for by time. On the basis of the analysis, a severity classification index was derived to establish the timeinfection (confirmed cases) ( Table 2 ) and timedeath relationships for the countries (Table 3) .

For the number of confirmed cases, Nigeria and Ghana were projected to be VERY LOW, South Africa and Sweden as LOW, United Kingdom (UK) as HIGH, while USA, Italy and Spain were projected to be VERY HIGH (Table 2) .

. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. For the number of deaths, Nigeria, Ghana and South Africa were projected to be VERY LOW, Sweden as LOW, United Kingdom (UK) and USA as HIGH, while Italy and Spain were projected to be VERY HIGH (Table 3) .

In order to establish the relationship between confirmed cases and death numbers, using available data, regression and correlation analysis were performed to establish the relationships in reported values. On the basis of the analysis, a classification index was derived and used to classify relationship of confirmed cases of COVID-19 infection and deaths over time for the countries. On the basis of the derived indices, the relationship for Nigeria, Ghana, South Africa, USA and Sweden were classified as LOW while time-death relationships for Italy, Spain and UK were classifies as HIGH (Table 4 ).

In order to group the countries on the basis of similarity in trends of confirmed cases and deaths, Similarity and distance indices (Bray Curtis and Euclidean) were computed among countries. These indices were further supported with hierarchical cluster analysis.

The results of the similarity and distance indices for the confirmed cases of COVID-19 infection are presented in Tables 5 -6 CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04.20.20072322 doi: medRxiv preprint grouping of the other countries was also established with USA, Italy and Spain in a subgroup, South Africa and Sweden in another sub-group while UK was a standalone, although more associated with SA-Sweden sub-group (Figs. 3 -4).

The results of the similarity and distance indices for the number of death cases are presented in Tables 7 -8 is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. 

The number of base pairs is approximately the same for all of the retrieved genome. They were within the range of 29417 bp-29903 bp. The retrieved sequence from the Nigerian population had the least genomic content of 29417 bp, while the South African population had the highest genomic content of 29902 bp. The multiple sequence alignment showed that majority of the genomic regions were highly conserved with little or no polymorphic attributes across the entire genome (Fig. 7) . This was further validated from the obtained phylogenetic tree bootstrap value, which revealed that the mutational rate is less significant, with little or no change across the population groups. The bootstrap scores were relatively zero, showing no significant change in the viral genome. The conservation scores for the entire sequence alignment was 98%.

For the phylogenetic analysis, an automated tree was generated after the consistent alignments. The resulting clustering based on phylogenetic analysis shows the relationships between the countries (Fig. 8) . 

Information collected on BCG vaccination policy in the selected African countries (Nigeria,

Ghana and South Africa) showed that all the countries have a current universal BCG vaccination policy, which is administered at birth. Nigeria has a multiple BCG vaccination policy while South Africa has a single vaccination policy. All the developed countries . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. Table 9 ).

showed that there is a significantly (p<0.05) higher infection rate in countries that do not have a current universal BCG vaccination policy compared to those countries with a vaccination policy (Figure 9 ). The percentage death due to COVID-19 is also significantly (p < 0.05) higher in countries without the BCG vaccination policy compared to countries with existing BCG policy ( Figure 10 ). However, there was no significant (p > 0.05) difference in infections rates in countries which had a universal vaccination policy in the past compared to countries that never had a universal vaccination policy ( Figure 11 ).

The results of the assessment of the relationship between malaria endemicity in sub-Saharan

Africa and occurrence of COVID-19 are presented in Table 10 and Figure 12 . The result shows there is a statistically significant (p<0.05) difference in the occurrence of COVID-19 cases between countries with high malaria endemicity compared to countries with low malaria endemicity. Countries with high malaria burden had significantly (p<0.05) lower cases of COVID-19 than those with low malaria burden. Spearman's rank correlation was also strong. As the number of malaria cases increased, the number of COVID-19 cases decreased (r = -0.08).

The influence of climatic condition depicted by temperature pattern on the COVID-19

infection was examined among the study countries. Figure 12 shows the computed spatial long-term mean temperature and Figure 13 shows the temporal mean monthly temperature . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. Figure 13 ). . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. Result of findings on healthcare approaches to management of COVID-19 in some African countries compared to the Europe and USA indicates a clear distinction in approach to management of the disease. Across the developed world, the preferred treatment approach has been to test, voluntary isolation at home, hospitalise for observation and treat, however, in Sub-Saharan Africa, the approach is basically test, mandatory isolation and treat (Table   11 ). 

The outcome of the analysis of COVID-19 data for the confirmed cases of infection and recorded deaths from the index case reporting to forty-five days study period indicates a clear cut division between the different countries being assessed. In particular, countries such as Nigeria and Ghana in sub-Saharan Africa were found to have consistently different pattern of confirmed cases of COVID-19 infection and recorded death cases compared to countries with more robust and well-resourced healthcare systems in Europe (Italy, Spain and UK) and

USA. During the study period, the number of confirmed cases of infection and associated deaths in sub-Saharan Africa were found to be very low (confirmed casesrange from 318 to 408; Deaths -6 to 10) compared to the exceeding high values (confirmed casesrange from . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. al. (2020) also reported that no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020) and suggested that immune targeting of these epitopes may potentially offer protection against this novel virus. Our observation therefore provides a bit of relief, as regarding the lesser mutation . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. Current guidance from the World Health Organisation (WHO) is that there is no known cure for this virus with 100% certainty however, research for vaccinations and cure continues fervently. In the interim, official guidance from global public health authorities is to test, test and test as many individuals of the population, practise social distancing, washing of hands with soap, use of hand sanitizers and then to proceed with caution when adopting any of the speculative treatment options. This very loose guidance has led to differential healthcare approaches to management of COVID-19 in different countries across the world. The outcome of our findings has revealed that fundamental differences exist between the healthcare systems of sub-Saharan Africa and those of Europe and America. In Europe and America, the preferred treatment approach has been to test, voluntary isolation at home, hospitalise for observation and treat, however, in sub-Saharan Africa, the approach is basically test, mandatory isolation and treat (see Table 11 ). So while the developed countries are concentrating on testing, the sub-Saharan African countries seem to be concentrating more on treating the diseases with some of the speculative re-purposed drugs.

Although there seems to be no basis for comparison in terms of resources and organisation between the healthcare systems in Europe and USA with that of sub-Saharan Africa, the outcomes with regards to number of recorded deaths or recovery rate of COVID-19 patients is staggering and very baffling. While a more resourced healthcare system in Europe and America has an outcome of 4064 (USA), 1789 (UK), 8464 (Spain) and 12428 (Italy) deaths after 44 days of reporting the 1 st index case, a country like Nigeria recorded 10 deaths after 44 days (www.worldodometer.com). So it does appear that something must be amiss because . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 24, 2020. . https://doi.org/10.1101/2020.04. 20.20072322 doi: medRxiv preprint Page 27 of 32 the numbers simply do not follow basic logic. It therefore seems that there may be a need to review the current healthcare approaches or guidance the mentioned developed countries have adopted to managing the COVID-19 illness. The outcomes in terms of the substantial huge number of recorded deaths seem to indicate a weakness in the healthcare approach. It may just be time to learn a lesson or two from the approach which the less developed countries have adopted to manage the disease in this time of emergency.

In Europe and America, the healthcare system is largely centrally controlled; public sector based and with rampant initiation of professional consequences if a wrong call is made. Also, there is controlled access to many drugs. However, in sub-Saharan Africa countries like Nigeria, the healthcare system is predominantly private, with lesser occurrence of initiation of professional consequences. The inability or difficulty of the healthcare workers in the more developed countries to adapt rapidly and explore the use of speculative drugs during this emergency maybe attributable to the stringent medical guidance, professional consequences and exposure to lawsuits associated with medical care in the countries. However, the differential outcomes from the two approaches in the management of this pandemic between the selected countries is indicative that in the enactment of emergency legislations for disease outbreaks, the congress or legislative bodies need to consider inclusion of clauses which are aimed at shielding the healthcare professionals of potential litigations that may arise from some decisions taking in their attempts to save lives during this type of novel disease outbreaks.

Apart from healthcare approach to management of the disease, a curious look at the healthcare systems in the different countries points to major obvious differences. Aside from the substantial differences in funding and manpower availability, there is almost unfettered access to most types of prescription drugs. Therefore, it is very possible that a large number of COVID-19 positives in Africa would have reached out to the pharmacist for different treatment sessions before eventually going for COVID-19 test. So could this early treatment occasioned by easy access to prescription drugs be a factor in the lowering death numbers being recorded in countries like Nigeria and Ghana? There is little doubt that in an emergency situation like the COVID-19 pandemic, the somewhat informal nature of healthcare practice in sub-Saharan Africa probably gives the healthcare professionals more room to operate by prescribing without formal guidance, certain drugs which have been reported in several media as being effective for the treatment of COVID-19, without . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 24, 2020. Emergency Operation Centre riding on facilities put in place during the Ebola crisis (Nature Medicine, 2020). There is no doubt that when another epidemic arises again, the experiences of the COVID-19 pandemic will make a lot countries to act differently and possible swiftly, which might affect the overall disease burden.

As the covid-19 pandemic is still unfolding, this paper has examined several factors in spatial differences associated with the disease over a 46 period of observation. The patterns and trends are still evolving and by the time the paper is published, significant changes could have occurred. The wide variation in the number of COVID-19 testing being carried out by the different countries will also have a major impact on the actual number of reported confirmed cases of infection. The number of deaths associated with COVID-19 during the period of study is however likely to follow the same trend as reported. A few selected countries have been chosen for evaluation and this may limit generalizability of findings. The findings however cuts across continents and this will provide scientific basis for detailed and more targeted research.

This study has revealed compelling spatial differences in the incidence and deaths from COVID-19 in selected countries in sub-Saharan Africa compared to Europe and USA over a 46-day observation period. The major factors attributed to the wide variation in the outcome of the COVID-19 disease burden in the countries examined are BCG vaccination policy, malaria endemicity, climatic condition (temperature) and differential healthcare approaches to management of the disease. The need to consider inclusion of clauses in national emergency legislations aimed at protecting healthcare professionals from lawsuits that can . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 24, 2020. .

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The authors acknowledge the opportunity to serve as volunteers of the UNILAG Consult COVID-19 Advisory Group (UCCAG).

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Page 29 of 32 arise from decisions taking in their attempts to save lives during this type of novel disease outbreaks was proffered. Further research is needed to confirm whether the spatial differences in incidence and deaths are sustained when the pandemic is resolved globally.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This study did not involve human or animal experimentation. All data sources are cited and acknowledged throughout the manuscript.

The authors have contributed equally to the publication.