COVID-19 Spread Patterns Is Unrelated to Malaria Co-Infections in Lagos, Nigeria

Malaria and COVID-19, though caused by different organisms, share a significant number of symptoms like fever, headaches, difficulty in breathing and fatigue. Therefore, determining if a patient is positive for COVID-19 or Malaria based on symptoms alone, might be misleading, especially during pandemic response. It has been reported that an individual begins to manifest Malaria symptoms between 10 - 15 days after infection with malaria parasite, although some individuals may be asymptomatic. Some COVID-19 infected patients, like Malaria, are also asymptomatic but could contribute to transmission of SARS-CoV-2 virus. These similarities in symptoms have led to misconception about COVID-19 being real and misdiagnoses of both infections, especially in Nigeria. However, there are possibilities that Malaria and COVID-19 could co-exist in some individuals thereby leading to misma-nagement and treatment of only one infection while neglecting the possibility of the patient being infected with both diseases. We aim to determine possible correlation between Malaria and COVID-19 in a Malaria endemic country like Nigeria. This study was carried out using the qPCR molecular testing ap-proach, a gold standard for COVID-19 testing and rapid diagnostic test kits to detect Malaria parasites in 617 individuals residing in urban settings. We demonstrated that COVID-19 and Malaria infection amongst adults in urban settings are unrelated thereby focusing on symptoms alone may result in mis-diagnosis. Our findings show that Malaria is not among the underlying med-How ical conditions strongly associated with increased risk for severe COVID-19 illness amongst adults in urban settings.


Introduction
In December 2019, a viral pneumonia disease COVID-19 caused by novel coronavirus SARS-CoV-2, was discovered in Wuhan City, Hubei Province, China and has since created a global disruption in the healthcare system [1]. The disease is transmitted by people in close contact with one another and through respiratory droplets when an infected person coughs or sneezes and the droplet enters the eyes, nose, and mouth [2]. The virulent nature and transmission pattern made the COVID-19 pandemic a serious global health threat [3].
Malaria is a disease burden majorly in the tropical and subtropical region which includes sub-Saharan Africa, Asia and Latin America in which sub-Saharan Africa results in 93 percent of malaria cases and 94% cases of malaria mortality [4]. In 2018, WHO reported that 50% of the malaria cases were reported by 6 African countries: Nigeria (25%), the Democratic Republic of the Congo (12%), Uganda (5%), and Côte d'Ivoire, Mozambique and Niger (4% each). Malaria is an acute febrile illness with flu-like symptoms such as fever, chills, headaches, nausea, vomiting, fatigue and body aches [4]. However, malaria could also cause severe illness majorly by the Plasmodium falciparum, such as severe anemia, kidney failure, cardiac arrest, hypoglycemia in pregnant women (after treatment with quinine), cerebral malaria-seizures, unconsciousness, abnormal behaviour or confusion which can eventually lead to DEATH [5]. People may also develop partial immunity, thus, resulting in asymptomatic infections especially in malaria endemic areas [5]. Risk factors in malaria are majorly children under the age of 5 which is responsible for 67% (272.000) of malaria deaths [6]. About 125 million pregnant women are also vulnerable to the infection, and in sub-Saharan Africa, about 200,000 infant deaths as a result of gestational malaria have been reported [7] [8]. Medications are now available for the treatment of malaria through the use of drugs such as chloroquine (CQ), doxycycline, quinine, mefloquine, atovaquone/proguanil (Malarone), which were used to treat malaria back then [9]. The first line antimalarial medicine for uncomplicated malaria is now Artemisinin Based Combination Therapies (ACTs) including artemether/lumefantrine and artesunate/amodiaquine [10]. Anti-malaria drugs could also be used by pregnant women and visitors travelling to malaria endemic countries [11]. Malaria preventive methods such as use of insecticides treated nets and indoor spraying of insecticides could also be used [12] (Astatkie, 2010). However, at the moment, there is no specific drug for COVID-19 [13] [14]. Though [15].
CQ is still commonly prescribed in these regions. Because CQ is now one of the mainstay therapies of COVID-19 all over the world, it has been suggested to play a role through innate immunity, in prevention of COVID-19 in malaria-endemic countries [14]. Hence, our study aims to determine the association that could possibly exist between malaria and COVID-19 in malaria endemic countries like Nigeria.

Methodology
The study was a cross sectional study, seeking to determine the prevalence of malaria among COVID-19 patients in Nigeria and the role it may play in the diagnosis and management of COVID-19 patients.

Enrolment of Participants into the Study
The participant was randomly selected among individual presenting for testing at the COVID-19 Drive-through testing centre after online pre-registration and informed consent obtained.

Laboratory Analysis
Blood and Swab samples (nasopharyngeal and oropharyngeal swab samples) were taken from participants for malaria and SARS-CoV-2 analysis, respectively. 2) Patients who tested negative for malaria but tested positive for COVID-19.
3) Patients who tested positive for both malaria and COVID-19.

4)
Patients who tested positive for malaria but tested negative for COVID-19.
In addition to tests of associations, we sought to determine the factors that could contribute to the patient category. To do this, we fitted a multinomial logistic regression using the patient category as the dependent variable. The model fitted was: All descriptive and inferential analyses were based on these 4 groups. All analyses were conducted using STATA 16 and an alpha level of 0.05 used to determine significance of all test statistics.
Of the 617 participants enrolled for this study, 489 (79.3%) were negative for  More than a half (58%) of the participants were male and they were the majority across all other groups but both malaria and COVID-19 positive had a male and a female. Of all the 617 participants, 374 (61%) were married, 236 (38%) were single, 3 (0.4%) divorced and 4 (0.6%) were separated. As shown in Table 1 below.

Spread Pattern for COVID-19 and Malaria
Though the number of malaria cases were exceedingly small, further analysis showed that Malaria prevalence was highest in Alimosho (33.3%, n = 3) and Eti-Osa 3, while Ikorodu, Kosefe, Shomolu and Surulere each had 1 patient testing positive for malaria.

COVID-19 Symptoms Presented by Study Participants
More than half of the respondents (52%, n = 320) reported that they had no symptoms. However, those who had symptoms mentioned fever (29%, n = 177), sore throat (24%, n = 145) and dry cough (20%, n = 121) as the top three symptoms. Other symptoms are as shown in Table 5 below.

Tests of Associations and Correlations
In addition to correlations, we tested the association of each category with the independent variables (Table 6). There was no variable found to be significantly associated to patient categories at alpha = 0.05 as shown on the table below.

Bivariate and Multivariate Analysis
Using the multinomial logit model, we

Discussion
The emergence of SARS-CoV-2 has brought about different postulations concerning its mode of transmission, symptoms associated with its infection, mortality rate etc. One of these said postulations lay emphasis on its relationship with malaria, it's been reported that malaria and COVID-19 share similar symptoms and could lead to misleading diagnosis, some regions (especially regions having high malaria prevalence) believe COVID-19 is the same as malaria [16]. These The findings from this study support the evidence that malaria endemicity has no association with COVID-19 infection. Since our study was conducted in a malaria endemic setting where it has been reported that half of the adult population could have at least one episode of malaria annually, our findings point towards a review of malaria incidences in these settings because of the low prevalence outcome. It could be argued that malaria parasite microscopy is the gold standard for malaria diagnosis, however, the RDT test kit used has been validated using microscopy, it is the most employed in malaria diagnosis in the country due to its low cost and rapid turnaround time. It has been opined that, prevalence of malaria is low in urban settings [17]. Our study is a mixed population of both urban and rural settings with participants spread across 18 local governments in Lagos State, with results showing that there is an occurrence of low malaria prevalence. Furthermore, the rainy season is here and malaria infection is expected to rise significantly during the rainy season which coincide with the period of this study, however, the low prevalence of malaria reported in this could mean a shift in paradigm as far as malaria endemicity is concerned. In addition, malaria is prevalent among children 5 years and below, however, this population was very few in our study [18]. This could be a limitation and the reason why malaria prevalence outcome from this study is exceptionally low.
More than half of the participants in this study were asymptomatic. However, fever, sore throat and dry cough are the most experienced symptoms among participants. This correlated with data from previous reviews on similar study in which the most common presenting symptoms are the same [19]. Our findings also provide a compelling evidence that disprove the theory that COVID-19 pandemic could complicate malaria diagnosis due to similarities in symptoms such as raised body temperature, headache and body ache that characterise both diseases as the two cases with COVID-19-Malaria Co-infection reported in our study were asymptomatic. Hence there is a need to further investigate factors responsible for low malaria prevalence at the height of COVID-19 spread in the country.
Though disease outbreaks affect men and women differently, this study showed that both genders responded to testing similarly and the male population had a similar COVID-19 infection rate with the female counterpart. Though contrary to a previous report from Bowale et al. [20], this outcome conforms to the study released by the Global Health 50/50 project which states that there are similarities in the COVID-19 incidence rate in both male and female [21].

Conclusion
In conclusion, there is no significant prevalence of malaria amongst patients