A Case of Malaria Patient with SARS-CoV-2 Antibody False-Positive

Background: The SARS-CoV-2 antibody detection are used to diagnose or exclude suspected COVID-19 patients as a supplement to nucleic acid detection. False-positive results of SARS-CoV-2 antibody have been reported but rarely associated with malaria. A case of malaria patient with SARS-CoV-2 antibody false-positive is described. Case presentation: A 24 year-old male returned from Côte d’Ivoire was diagnosed Plasmodium falciparum by Malaria rapid diagnostic test. The patient had suspicious exposure to COVID-19. His SARS-CoV-2 IgM antibody was positive one day before admission and turned negative on the 18th day of admission, while the IgG antibody and nasopharyngeal swabs SARS-Cov-2 nucleic acid had been negative. Conclusion: Malaria might cause false positive for SARS-CoV-2 IgM antibody. A careful interpretation of the SARS-CoV-2 antibody result is useful to avoid wasting medical resources especially malaria-endemic areas.

Refer to Table 1 for the results of SARS-Cov-2 IgM and IgG antibodies, SARS-Cov-2 nucleic acids, malaria rapid diagnostic test and microspic exarmnation of blood lms. The SARS-Cov-2 IgM antibody has been tested positive many times and turned negative after 18 days, while the IgG antibody and nasopharyngeal swabs SARS-Cov-2 nucleic acid have been negative. Malaria rapid diagnostic test suggested P. falciparum infection. Plasmodium blood lms tested negative multiple times. The patient was diagnosed P. falciparum by Malaria rapid diagnostic test. He was treated with artesunate for 3 days (September 10 to 12, 2020), sequential dihydroartemisinin and piperaquine phospate tablets for 2 days (September 13 to 14, 2020).

Discussion
SARS-Cov-2 enters the body to cause an immune response, with IgM antibody appearing rst, and then IgG antibody. After the appearance of IgG antibody, the concentration will continue to increase, and the IgM antibody will continue to decrease until it disappears. IgG antibody will exist for a long time. By monitoring the dynamic changes of IgM and IgG antibody, it is helpful to diagnose the SARS-Cov-2 infection and judge the infection status. IgM antibody is produced by the body's initial immune response, with fast production speed and short duration, as indicator of early infection; IgG antibody is produced later than IgM and has a long duration, and can be used as indicator of infection and previous infection.
Studies have shown that after SARS-Cov-2 infects the body, antibodies can be detected usually in 5 to 10 days [2] . Guo L et [3] research showed SARS-Cov-2 speci c IgM antibodies were detected at 5 days (interquartile range [IQR], 3 to 6 days) after onset, while IgG antibodies appeared at 14 days (IQR, 10-18 days). Zhao J et [4] found over 90% of patients were seropositive for IgG antibodies after day 14 of illness. Our study showed that IgM antibody was persistent positive for 18 days, while IgG antibody and SARS-Cov-2 nucleic acid continue to be negative, so IgM antibody was judged to be false positive.
Currently, speci c antibody (IgM, IgG) detection tests mainly include colloidal gold method (lateral ow immunoassays, LFIA), enzyme-linked immunosorbent assays (ELISAs), chemiluminescence immunoassays, etc [5] . Some studies have reported false positives of SARS-Cov-2 antibodies [6,7] . The reasons are related to the following: different test kits used by various testing institutions, different settings of the positive cut-off value of the test kits, different testing instruments, differences in the level of operators, and patients situation and so on [8] .
The colloidal gold method is a rapid diagnostic test based on the principle of using colloidal gold as a tracer for immunoassay. The operation of the colloidal gold method is simple, and the qualitative analysis of IgM and IgG antibodies can be performed without additional equipment [9] , moreover the positive or negative result can be judged by visual observation without the positive cut-off value. However, SARS-Cov-2 antibody test may have false positive results due to the presence of some interfering substances in clinical samples. Interfering substances include endogenous substances and exogenous substances. Endogenous substances include: rheumatoid factor, heterophile antibodies, complement, anti-mouse Ig antibodies induced by the use of murine antibodies for treatment or diagnosis, and lysozyme, etc [6,8,10] . Exogenous substances include: specimen hemolysis, specimen storage time is too long, etc [8] . Yadouleton A et al. [11] used ELISAs to test COVID-19 cases(n = 8) and fever of unknown origin cases (as prepandemic controls, n = 60). They found < 25% false-positive results likely due to unspeci c immune responses elicited by acute malaria. The higher proportion of SARS-CoV-2 false-positive in acute malaria patients compared with likely subacute or chronic malaria patients. In our case, we also considered that malaria caused a non-speci c immune response leading to false positive for SARS-CoV-2 IgM antibody.
Conclusion SARS-CoV-2 antibody test may be useful for diagnosis, risk management and mitigating transmission. However, false-positive results lead to unnecessary quarantine and resource allocation. So in a malaria-endemic area, the results of the SARS-CoV-2 antibodies need to be interpreted carefully to avoid wasting medical resources and implementing unnecessary infection control interventions.
Declarations Figure 1 Timeline of suspicious exposure to COVID-19 and symptom Principle of SARS-Cov-2 IgM/IgG antibody-detecting rapid diagnostic tests Note: SARS-Cov-2 rapid diagnostic test is a lateral ow immunochromatographic device that detects antibody. It has two cards test device (IgM and IgG cards). A sample of blood including IgM or IgG antibody is mixed with labeled Ab (Anti-human IgM/IgG antibody). Speci c SARS-Cov-2 IgM/IgG antibody is captured by SARS-Cov-2 antigen and trapped on the test line. Other labeled antibody is trapped on the control line.