key: cord-0877338-jhr6s2fk authors: Colebunders, Robert title: COVID-19: The African enigma date: 2021-04-24 journal: Colombia medica DOI: 10.25100/cm.v52i2.4816 sha: 64a44a2bb2c2ca9308477db925d4457240623d64 doc_id: 877338 cord_uid: jhr6s2fk nan Article: https://colombiamedica.univalle.edu.co/index.php/comedica/article/view/4613 We read with interest the paper by Guerrero et al "COVID-19: The Ivermectin African Enigma" 1 . In an ecological study they compared COVID-19 related mortality and infection rates between APOC (African Programme for Onchocerciasis Control) and non-APOC countries. After adjusting for Human Development Index (HDI) and number of performed test, COVID-19 mortality and infection rate were respectively 28% and 8% lower in non-APOC countries compared to APOC countries 1 . The authors suggested that this difference may be related to the community directed treatment with ivermectin (CDTI) programs established in APOC countries. We agree that it remains to be explained why a lower COVID-19 mortality is observed in many APOC countries compared to other parts of the world. However, we do not believe that this is related to CDTI programs. Indeed, in APOC countries ivermectin is distributed only once (most countries) or twice a year 2 . Moreover, April 1 st 2020, because of the COVID-19 pandemic, CDTI programs were interrupted and were only recently restarted 2 . Ivermectin has an in vitro anti-COVID-19 effect 3 and also certain clinical trials suggested a beneficial effect of ivermectin on COVID-19 disease outcome 4 . However, in a recent small double blind, randomized control trial in Colombia, five days of ivermectin, at a 10 times the recommended dose, did not reduce the duration of symptoms of mild COVID-19 disease compared to placebo 5 . Given the half-life of ivermectin, approximately 18h 6 , it is unlikely that CDTI, only one dose of ivermectin once or twice a year, may be able to reduce COVID-19 related mortality. Many factors could explain the lower COVID-19 mortality in APOC countries 7 . One of them could be exposure to parasitic infections and the immune response induced by these infections. For example, for P. falciparum, a parasitic infection highly prevalent in APOC countries, it has been hypothesised that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis and therefore may protect persons with a recent P. falciparum infection against severe COVID-19 disease 8 . Helminth infections, such as onchocerciasis, may down regulate immune responses 9 and potentially inactivate the inflammatory signalling pathways that may induce acute respiratory distress syndrome (ARDS), one of the causes of death in COVID-19 infected persons 10 . COVID-19: The Ivermectin African Enigma What does the COVID-19 pandemic mean for the next decade of onchocerciasis control and elimination? Ivermectin, antiviral properties and COVID-19: a possible new mechanism of action The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial The pharmacokinetics and interactions of ivermectin in humans--a mini-review Why is There Low Morbidity and Mortality of COVID-19 in Africa? Less Severe Cases of COVID-19 in Sub-Saharan Africa: Could Co-infection or a Recent History of Plasmodium falciparum Infection Be Protective? Front References COVID-19: The Ivermectin African Enigma A COVID-19 prophylaxis? Lower incidence associated with prophylactic administration of ivermectin COVID-19 in Africa: Dampening the storm? Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial