key: cord-0888070-l7wx4pun authors: Kangbai, Jia Bainga; Babawo, Lawrence Sao; Kaitibi, Daniel; Sandi, Anthony A.; George, Angela Magdalene; Sahr, Foday title: Re-reading ACT, BCG, and Low COVID-19 in Africa date: 2021-01-12 journal: SN Compr Clin Med DOI: 10.1007/s42399-020-00704-3 sha: c7b5b95de333ea7ad2ed550cf0e723808a9076a3 doc_id: 888070 cord_uid: l7wx4pun October 11, 2020, marks the seventh month since the World Health Organization (WHO) officially declared COVID-19 a pandemic. Unlike other coronavirus diseases, there is a geographically disproportionate distribution of the incidence of COVID-19 cases around the world. We observed a significantly high COVID-19 cases and deaths in countries and territories with no or very small number of malaria cases or no or low national TB cases in 2018. We speculate that the high incidence of COVID-19 cases and deaths in countries less affected by malaria is partly due to overexposure to malaria which led to the regular use of the artemisinin anti-malaria drugs as well as the regular use of bacillus Calmette-Guérin (BCG) vaccine for TB prevention. The vaccine produced an almost life-long immunity to TB and meningitis to its recipients. We are thus calling for a COVID-19 containment and clinical management protocol that will incorporate the use of the anti-malaria ACT drug cocktail and BCG vaccine on compassionate ground. million TB-related deaths globally in 2018, a reduction of 2 and 5%, respectively, from 2017. Two-thirds of the global TB cases were in eight countries: India (27%), China (9%), Indonesia (8%), Philippines (6%), Nigeria (4%), Bangladesh (4%), and South Africa (3%) [2] . Of those countries and territories with > 11,000 COVID-19 cases as of October 12, 2020, only Andora (399 malaria cases per million) and Brazil (320 malaria cases per million) recorded comparatively high incidence of malaria in 2018 [2] . We observed a significantly high COVID-19 cases and deaths in countries and territories with no or very small number of malaria cases. For 1 (per million at risk), the COVID-19 incidence rate decrease by 10.00 (per million at risk). Additionally, holding the number of malaria cases in the model constant, as the TB cases increase by 1 (per million at risk), the COVID-19 incidence rate decreases by 9.90 (per million at risk). The AUC for the ROC curve analysis was 89.5%, which shows that COVID-19 incidence rate was a good classifier for malaria-free countries or those countries with limited malarial infections (4 or less malaria cases per 1 million at risk). We speculate that the low incidence of COVID-19 cases and deaths in countries highly affected by malaria is partly due to overexposure to malaria which led to the regular use of the artemisinin anti-malaria drugs, as well as the use of BCG vaccination for TB. Our speculation is based on the fact that several African countries that are endemic to malaria continue to record very low COVID-19 [4, 5] incidence rates compared to non-Africa countries that are not endemic to malaria. We do not go along with the idea that the low COVID-19 incident rates among black people may be due to genetic susceptibility since COVID-19 severity among African-Americans in the USA is very high. Additionally, we are also speculating that the low COVID-19 incidence rates recorded by malaria endemic countries may be due to anti-malaria immunity produced by antibodies (IgG) following exposure to plasmodium-specific antigens. Overexposure to a particular pathogen ensures a huge stockpile of antigen-specific antibodies for that pathogen. One study reported that people who have antibodies to different pathogens are known to be protected against COVID-19 [6] . The IgG that is produced by plasmodiumspecific antigens can recognize the different COVID-19 glycoproteins (GPs) including membrane GPs such as spike GPs and GPs that have acetyl esterase and hemagglutination properties [7] , thereby either providing protection against COVID-19 or producing a much milder infection [8] . Another possible explanation of the low transmission of COVID-19 in countries endemic with malaria is the wide use of the anti-malaria artemisinin drug. Unlike chloroquine that was withdrawn in the late 1990s due to growing resistance to it by the plasmodium pathogen [9] [10] [11] [12] , most (n = 65/67, 97%) malaria endemic countries including 41 Africa countries adopted artemisinin combine terapy (ACT) as their first line of treatment for uncomplicated malaria in 2000 [13] . One study has demonstrated in vitro the clinical effectiveness of artemisinin in the treatment of COVID-19 [14] . The low COVID-19 incidence rates in countries with high TB cases as reported in 2018 may be associated with the wide use of the bacillus Calmette-Guérin (BCG) vaccine which offers protection against both TB and meningitis. BCG vaccine is most commonly administered to persons below 35 years and who are at high risk of becoming infected with TB in their life time. The vaccine produced an almost life-long immunity to TB and meningitis recipients. However, there have been opposing views whether BCG can offer protection from COVID-19 infection [15] [16] [17] . We are also aware that Africa's low COVID-19 cases may have been due to the limited COVID-19 testing as well as the limited COVID-19 testing data coming from the continent. With such limitations, it is still difficult to conclude whether the spread of COVID-19 in Africa is minimal. We also agree with those who are claiming that Africa population may have been spared the full brunt of the pandemic because of the continent's high youthful population, low prevalence of cardiovascular diseases, limited international connectivity, and the continent's strong public health systems. The Africa continent with 54 countries, different infrastructures, and diverse health policies is yet characterized by having a youthful population. One paper pointed out that having a large youthful population may mean many infected COVID-19 patients not displaying symptoms thereby placing many other people at risk than would symptomatic individuals [18] . In one Chinese study, only 1% of the 44,672 COVID-19 cases were below 10 years [19] , while another study reported that children just like adult got infected and that community transmission of COVID-19 may be link to pediatric COVID-19 cases [20] . Comparatively to Europe and North America, Africa continent has lower prevalence of noncommunicable diseases (NCD) such as cardiovascular diseases, cancer, and diabetes, all of which places COVID-19 patients at high mortality risk. According to the World Health Organization, 17.9 million people died annually from cardiovascular diseases, 9.0 million died from cancers, and 3.9 million people died annually from respiratory diseases, while 1.6 million people died from diabetes [21] . There has been a rising trend in the prevalence of NCD in Africa, but the continent is still trailing Europe and North America in terms of NCD morbidity and mortality; the burden of disease in Africa is still dominated by infectious diseases [22] . We are thus calling for a COVID-19 containment and clinical management protocol that will incorporate the use of the anti-malaria ACT drug cocktail and BCG vaccine on compassionate ground. Additionally, future studies regarding the clinical effectiveness of ACT and BCG vaccine on COVID-19 infection will be desirable. World Malaria report 2019″ report at a glance. World Health Organisation World Health Organisation Incidence of coronavirus disease (COVID-19) and countries affected by malarial infections Comparative analysis revealed reduced spread of COVID-19 in malaria endemic countries. medRxiv preprint Safety recommendations and medical liability in ocular surgery during the COVID-19 pandemic: an unsolved dilemma Coronavirus disease 2019 (COVID 19) and malaria have anti glycoprotein antibodies a role? Med Hypotheses Autoimmunity, phospholipid-reacting antibodies and malaria immunity Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi Return of chloroquine antimalarial efficacy in Malawi Adoption of the new antimalarial drug policy in Tanzania-a cross-sectional study in the community Increasing antimalarial drug resistance in Uganda and revision of the national drug policy A major transition in malaria treatment: the adoption and deployment of artemisinin-based combination therapies Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: in vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate Lack of evidence for BCG vaccine protection from severe COVID-19 BCG vaccine protection from severe coronavirus disease 2019 (COVID-19) BCG vaccination induced protection from COVID-19 Are children less susceptible to COVID-19? Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention Epidemiology and transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts Noncommunicable diseases and mental health Burden of non-communicable diseases in sub-Saharan Africa, 1990-2017: results from the global burden of disease study Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Competing Interests All authors declare they have no competing interest.