Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness — United States and Puerto Rico, April 2020–March 2021

Muñoz‐Jordán, Jorge L.; Cardona, Jaime; Beltrán, Manuela; Colón, Candimar; Schiffer, Jarad; Stewart-Clark, Evelene; Zellner, Briana; Semenova, Vera; Li, Yikun; Jia, Lily T.; Maniatis, Panagiotis; Pawloski, Lucia; Adams, Laura; Paz–Bailey, Gabriela; Rivera‐Amill, Vanessa; Medina, Freddy A.

doi:10.15585/mmwr.mm7110a3

Cited by 13 publications

(16 citation statements)

References 9 publications

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“…The different reactivity profiles seen for coronavirus, HIV-1, or flavivirus antigens indicated that the SARS-CoV-2, SARS-CoV-1, and MERS-CoV responses observed among samples from Africa were not caused by high overall reactivity levels in the samples irrespective of the antigen and suggested that the responses could be coronavirus-specific. A previous report showed cross-reactivity between SARS-CoV-2 and Zika virus ( 31), but we saw no evidence of cross-reactivity against 8 Zika virus antigens tested, which aligns with another study (32). Multiple studies showed associations between SARS-CoV-2 antibody responses and malaria antigens (11,(33)(34)(35)(36).…”

Section: Discussionsupporting

confidence: 89%

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand

Li¹,

Merbah²,

Wollen-Roberts³

et al. 2022

Emerg. Infect. Dis.

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C OVID-19 clinical manifestations range from asymptomatic infection to death. Whether prior immune responses to human coronaviruses affect responses to SARS-CoV-2 remains unclear. At the population level, disparities in COVID-19 outcomes have been observed across geographic regions. For instance, countries in Africa have reported lower mortality rates than high-income countries, which can be attributed to the small percentage of persons in the oldest age groups and to underreporting (1,2). Previous responses to endemic coronaviruses also could influence how different populations responded to SARS-CoV-2.Findings conflict as to whether previous coronavirus antigen responses cross-react with SARS-CoV-2. Depending on the antigen and cohort tested, binding responses have been detected in prepandemic samples at varying frequencies, but neutralizing antibodies have been identified in fewer samples (3-8). Some studies of prepandemic samples indicated that neutralizing responses to endemic coronaviruses could protect against SARS-CoV-2 infection, but the effects of previous coronavirus responses on SARS-CoV-2 have not been clearly elucidated (6,7,9-13).To investigate coronavirus-specific antibody responses in different settings, we analyzed 2,565 samples collected during 2013 through early 2020 from persons living with HIV-1 (PLHIV) and persons without HIV in Kenya, Nigeria, Tanzania, Uganda, and Thailand. We profiled antibody binding responses to coronavirus antigens, including spike (S) and nucleocapsid (N) proteins of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and 4 endemic coronaviruses. We further evaluated a subset of samples with strong binding responses for neutralizing, antibody-dependent cellular

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Section: Discussionsupporting

confidence: 89%

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand

Li¹,

Merbah²,

Wollen-Roberts³

et al. 2022

Emerg. Infect. Dis.

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“…Another study 34 found some IgM and IgA rather IgG false-positivity for SARS-CoV-2 in febrile illness from dengue in Thailand, but the false-positivity tended to be even more frequent for febrile illness from non-dengue cases (including apparently malaria). In a study with samples from Puerto Rico and USA, 35 dengue did not induce cross-reactive antibodies to SARS-CoV-2 and the same was true in dengue samples from Indonesia, 36 Colombia 37 and travel clinics. 38 Conversely, 5 of 17 archival dengue samples from India 39 had cross-reactive antibodies to SARS-CoV-2 and another study 40 found 22% crossreactivity in samples from an Israel center (unspecified country of provenance); however, it is unknown whether any positive samples could be from patients who also had a history of malaria.…”

Section: Discussionmentioning

confidence: 76%

“…SARS-CoV-2 infection has been described to frequently produce cross-reactive antibody activity to dengue, 36,37,40 but not seen in all studies. 35 Anti-SARS-CoV-2 antibodies may also have a protective role for dengue 33 and, interestingly, reported dengue cases and deaths have declined in 2020-2022 after a peak in 2019. 41 In-silico analysis shows possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein, 40 but the evidence is again stronger for malaria, where cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein.…”

Section: Discussionmentioning

confidence: 99%

Pre-pandemic cross-reactive humoral immunity to SARS-CoV-2 in Africa: systematic review and meta-analysis

Ioannidis

Contopoulos‐Ioannidis

2022

Preprint

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Background: Low numbers of recorded COVID-19 deaths in Africa may be due to undercounting and/or protection due to demographic and/or other factors, including pre-existing immunity. Several studies have assessed pre-pandemic samples for anti-SARS-CoV-2 antibodies with heterogeneous results. Methods: We performed a systematic review and meta-analysis of studies evaluating pre-pandemic African samples for anti-SARS-CoV-2 antibody activity using pre-set assay-specific thresholds for seropositivity. Data where assay thresholds were calibrated on African populations were excluded. Searches used PubMed (September 13, 2022), reference lists of retrieved papers and citing articles (Google Scholar). Data were extracted independently by two authors on study and assay characteristics, and number of positive and tested samples. Datasets were classified according to malaria, dengue, and HIV burden. Proportions of seropositivity were combined with random effects meta-analysis. Results: 22 articles with 117 datasets were eligible, including 2,971 positives among 21,988 measurements (13.5%) with large between-dataset heterogeneity. Positivity was higher for anti-S1 (25%) and lower for anti-RBD antibodies (8%). Positivity was non-significantly higher for IgM than for IgG antibodies. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (17%, 95% CI, 15-19%) versus 1%, 95% CI 0-2% in other datasets). There were modest differences according to dengue burden (15% versus 11%). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (seropositivity 19% and 12%, respectively), and not without high malaria burden (seropositivity 2% and 0% with and without high dengue burden, respectively). There were modestly lower proportions of positivity in datasets with >10% of HIV-infected participants (8% versus 15% in others), but no association according to HIV serostatus in individual samples (summary odds ratio 0.97, 95% CI, 0.55-1.70). Interpretation: Pre-pandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity that tracks especially with malaria.

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“…As a control to eliminate the possibility of coinfection in the sera, these studies used archived sera, that is, sera obtained before the COVID-19 pandemic. These studies are summarized in Table 2 31–43 …”

Section: Resultsmentioning

confidence: 99%

Occurrence of False-Positive Tests and Cross-reactions Between COVID-19 and Dengue With Implications During Diagnosis: A Mixed Evidence Synthesis

et al. 2023

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This review aimed to assess the occurrence of false-positive serological reaction between dengue and coronavirus disease 2019 (COVID-19) and its implications for diagnosis. Evidence syntheses were conducted by systematically reviewing available literature using multiple databases, including Web of Science, PubMed, Google Scholar and medRxiv. Among a total of 16 presented cases from clinical settings, cross-reaction to COVID-19 serological tests was observed in two (12.5%) dengue-positive patients, while 14 patients (87.5%) confirmed positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showed a cross-reaction with dengue serological tests, leading to misdiagnosis and mismanagement by attending clinicians. Of 1789 SARS-CoV-2-positive sera, cross-reaction to dengue serological tests was observed in 180 sera (10%), which is higher than the cross-reaction observed for SARS-CoV-2 in archived pre-COVID-19 sera positive for a dengue infection (75 of 811, 9.2%, P = 0.674). Clinicians in tropical regions are therefore advised to interpret serological tests with caution and use a more pragmatic approach to triage these infections.

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Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness — United States and Puerto Rico, April 2020–March 2021

Cited by 13 publications

References 9 publications

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand

Pre-pandemic cross-reactive humoral immunity to SARS-CoV-2 in Africa: systematic review and meta-analysis

Occurrence of False-Positive Tests and Cross-reactions Between COVID-19 and Dengue With Implications During Diagnosis: A Mixed Evidence Synthesis

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