Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda

Abstract

Background The potential effects of SARS-CoV-2 and Plasmodium falciparum co-infection on host susceptibility and pathogenesis remain unknown. We aimed to establish the prevalence of malaria and describe the clinical characteristics of SARS-CoV-2 and P falciparum co-infection in a high-burden malaria setting. Methods This was an exploratory prospective, cohort study of patients with COVID-19 who were admitted to hospital in Uganda. Patients of all ages with a PCR-confirmed diagnosis of SARS-CoV-2 infection who had provided informed consent or assent were consecutively enrolled from treatment centres in eight hospitals across the country and followed up until discharge or death. Clinical assessments and blood sampling were done at admission for all patients. Malaria diagnosis in all patients was done by rapid diagnostic tests, microscopy, and molecular methods. Previous P falciparum exposure was determined with serological responses to a panel of P falciparum antigens assessed using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation, and serum biochemistries. The main outcome was overall prevalence of malaria infection and malaria prevalence by age (including age categories of 0–20 years, 21–40 years, 41–60 years, and >60 years). The frequency of symptoms was compared between patients with COVID-19 with P falciparum infection versus those without P falciparum infection. The frequency of comorbidities and COVID-19 clinical severity and outcomes was compared between patients with low previous exposure to P falciparum versus those with high previous exposure to P falciparum . The effect of previous exposure to P falciparum on COVID-19 clinical severity and outcomes was also assessed among patients with and those without comorbidities. Findings Of 600 people with PCR-confirmed SARS-CoV-2 infection enrolled from April 15, to Oct 30, 2020, 597 (>99%) had complete information and were included in our analyses. The majority (502 [84%] of 597) were male individuals with a median age of 36 years (IQR 28–47). Overall prevalence of P falciparum infection was 12% (95% CI 9·4–14·6; 70 of 597 participants), with highest prevalence in the age groups of 0–20 years (22%, 8·7–44·8; five of 23 patients) and older than 60 years (20%, 10·2–34·1; nine of 46 patients). Confusion (four [6%] of 70 patients vs eight [2%] of 527 patients; p=0·040) and vomiting (four [6%] of 70 patients vs five [1%] of 527 patients; p=0·014] were more frequent among patients with P falciparum infection than those without. Patients with low versus those with high previous P fal...

The immunological nature of the pathological effects of SARS-CoV-2 and other pathogens

“…The observation in the African nation of Uganda that patients with low versus those with high previous Plasmodium falciparum exposure have an increased frequency of severe or critical COVID-19, which was presented in a study that highlights the importance of understanding the potential clinical and therapeutic implications of overlapping co-infections, 16 when viewed in the light of the results of our investigation, leads us to the conclusion that malaria is one of the diseases in the immunological spectrum to which COVID-19 belongs. The consequence of this conclusion is that those who have survived despite high previous Plasmodium falciparum exposure are more likely to be exposed to conditions that permit immune mechanisms to reduce the severity of the diseases in that spectrum by blocking the pathway through which they are produced by the gravity-like unobservable in response to their different causes and therefore more likely to be those in whom the frequency of severe or critical manifestations of such diseases will be lowest.…”

Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

“…This presence has been related to a lower COVID-19 morbidity/mortality in this populations [42] , [43] . Plasmodium and human immunodeficiency virus (HIV), both microorganisms being endemic in Africa, have been shown to induce in patients nNAbs that can cross-react with SARS-CoV-2, but these antibodies do not correlate with more severe forms of COVID-19 disease [44] , [45] , [46] . Polyclonal plasma from HIV-infected children cross-reacts with SARS-CoV-2 but, to our knowledge, there are no data in the literature on their possible involvement in ADE [47] .…”

Clinical characteristics, complications, and predictors of outcome of hospitalized adult Sudanese patients with COVID‐19 and malaria coinfection in Sudan: A multicenter retrospective cross‐sectional study

“… 39 And regarding comparison with other co‐infection studies, the overall mortality among our coinfected participants was 40.4% ( n = 63), in contrast to a cohort study done in Uganda that showed a mortality rate among COVID‐19 and malaria coinfected patients of only 3%. 40 We believe that coinfection has a vital role prompting a high mortality rate due to the increased inflammatory response; also, we assume the mortality rate in our study to be inflated due to other factors; such as the lack of fundamental resources (lifesaving resources and adequate staff). P. falciparum overall mortality is difficult to obtain due to scarcity of data; but as stated in a study, P. falciparum mono infection overall mortality in Sudan, was approximately 0.13% in 2019.…”

“…Our findings align with a study done in Uganda, where fever (21%, n = 70) and shortness of breath (19%, n = 70) were the second and fourth most common symptoms among COVID‐19 and malaria coinfected patients, respectively. 40 Although both symptoms are considered among the most to occur, there is a substantial difference between the prevalence of occurrence among the two studies. This might be due to the treatment‐seeking behavior of our patients, as many individuals wait until symptoms arise before seeking treatment.…”