The study area has been endemic to vector-borne diseases for several years [11]. Both diseases, included in this study, i.e., malaria and dengue, have the potential to become fatal in many situations. Currently, the world is in the post-COVID-19 pandemic era. However, future global outbreaks of a similar nature and magnitude cannot be ruled out. Infection with COVID-19 has already been found to cause long-term immunological alterations in the human body [14]. A study by R. Ramakrishnan et al. revealed that being infected with the COVID-19 virus can cause immune exhaustion, post-viral autoimmunity, dysregulated immune metabolism, and microbial dysbiosis, contributing to the post-acute effects of COVID-19 [14]. Research has also indicated a possibility of cross-immunity between certain pathogens, suggesting that exposure to one might protect against another during a future infection. For instance, prior infection with malaria has been linked to reduced susceptibility to chikungunya [15,16,17]. Thus, there is a need for robust evidence on the impact of past COVID-19 infection on the severity of diseases like malaria and dengue. However, as noted, there is a lack of literature on how prior COVID-19 infection can affect the severity of these diseases.
Although the causative agents for dengue and malaria are different, both infections are transmitted through the bite of infected mosquitoes. Hence, the environment and host factors of both diseases are similar. Also, the pathogenesis of COVID-19 is remarkably similar to that of malaria and dengue, especially concerning the role of inflammation. In COVID-19, the virus triggers a strong inflammatory response, only to progress, in severe cases, to a cytokine storm. They continue to release inflammatory mediators, which not only harm different organs but also damage the vascular endothelium, resulting in endothelial dysfunction and structural damage. This endothelial injury further leads to hematologic derangements and plasma leakage, defining the patient’s clinical course. The convergence of these pathways- systemic inflammation followed by endothelial cell compromise and plasma leakage is also a key aspect of pathophysiology underpinning severe malaria and dengue. Furthermore, similarities have been identified in the interaction with host cells, specifically using the ACE2 receptor by the malaria parasite and the COVID-19 virus. Genetic variations in ACE1 and ACE2 have also been associated with malaria resistance, potentially impacting susceptibility to COVID-19 [18].
The present study found a significant association between a history of COVID-19 infection and the severity of dengue and malaria infections. To this effect, our study is the first to our knowledge to descriptively evaluate this association. Out of the total participants in our study, 22.9% (n = 67) reported having prior COVID-19 infections, which were mild and never progressed to severe disease.
Dengue fever can progress to dengue haemorrhagic fever and dengue shock syndrome if not monitored and managed promptly [19]. Although vaccines and newer drugs are developed and being tested for dengue infection, supportive care remains the mainstay of management in many countries [20]. Dengue virus exists in four different forms (serotypes 1–4), increasing the likelihood of repeated infections throughout a person’s life [21]. The Case fatality of dengue can vary from < 1–15%. Similarly, malaria is a potentially fatal infection with high morbidity and mortality if it reaches the stage of severe malaria. The progression of these diseases to their severe form can be different due to various factors like increasing age, gender, type of occupation and access to quality health care [22, 23]. In the current study, we focused on the severe cases at the time of data collection. Progression from mild or moderate disease to severe disease (malaria and dengue) was not captured.
The findings of our study suggest immunological interaction between the two diseases, although the route of entry and pathogenesis are different for both. Although these studies suggest similarities in the immunological reactions of the two pathogens, the exact sequelae and consequences of this interaction remain unclear, and hence, it is necessary to identify the factors that can influence the severity of vector-borne diseases, especially in endemic regions.
A review article by Harapan H. et al. in Indonesia to describe the impact of COVID-19 on dengue infection in dengue-endemic countries concluded that due to the identical early-stage symptoms and test characteristics of both illnesses, accurate diagnosis and therapy are made difficult. Moreover, some reports have shown cross-reactivity between serology testing for DENV and COVID-19 virus antibodies [24].
A study done by Wang et al. found that age, gender, socioeconomic status, occupation, and geographical location are factors that can affect the severity of malaria. They found that children, pregnant women, and the elderly are more prone to severe malaria [25]. However, our study included only adults, and it was found that those aged more than 30 years were more at risk of severe malaria infection, even though there was no statistical significance. Their finding (Wang et al.) that males have higher chances of developing severe malaria was similar to our study finding, where 72.7% of the males with malaria developed complications.
A systematic review done by Abraham Degarege et al. in 2021 reiterated that lack of education, low socio-economic status, which in turn can lead to poor housing and living conditions, are factors which increase the risk of severe malaria. This is in line with our study findings in which those aged > 30 years, males, those engaged in unskilled occupations, had education below high school and lower socio-economic classes were more at risk of developing severe malarial disease.
Socio-demographic characteristics of the participants like age, education, education, occupation, and socioeconomic status, can also determine the impact of the disease as reported by M. Rajesh Kumar Rao et al. in their study, which was carried out in the year 2018 [26]. In our study, those participants aged > 30 years had higher chances of developing severe dengue infection compared to those aged < 30 years. However, the risk was found to be more among those with a history of COVID-19 infection in the past. Also, males had more chances of developing severe malaria as compared to females, and the risk increased in participants with a history of COVID-19 infection. It was found from our study that those participants who received 3 doses of the COVID-19 vaccine had a higher chance of developing severe malaria as compared to those who received 2 doses of the vaccine. This may be due to the immune response following vaccination, which is similar to the response after an infection [26, 27].
The findings from this study could be used to follow up on those with a history of COVID-19 and assess the possibility of severe malaria or severe dengue in them. Also, when a patient with malaria/dengue is asked for a history of COVID-19 infection and vaccination as a routine practice so that progression to severe illness can be anticipated and close monitoring can be done as precautionary measure. Based on this, the policymakers can plan and implement additional precautionary measures to prevent severe malaria/dengue infection especially in endemic regions.
Although, in this study, an association was evaluated and established; however there is a need for further immunohistochemical and logitudinal studies to establish and strengthen biological plausibility. Thus, it will help in devising and revising health policies towards preventive measures towards malaria and dengue. In the backdrop of uncertainties, such evidence will help to gear up the preventive measures to malaria and dengue.
One of the study’s main limitations was that none of the participants reported a history of severe COVID-19 infection. There is also a possibility of recall bias among them about the history of COVID-19. All the participants were vaccinated against COVID-19, which can also mimic a similar immune response. Also, vaccination could mask the immunological pathway, and it could lead to indistinguishability to a certain extent. We used a sequential sampling technique in this study, considering the feasibility aspects and changing trend of the vector-borne disease burden. This could bring about some element of selection bias and generalizability issues. In addition, this study could not assess the causality and immunological markers due to feasibility and operational reasons.