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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 80-83

Effect of severe acute respiratory syndrome coronavirus 2 antibodies on outcomes of dengue infected children: A retrospective observational study


Department of Pediatrics, Sri Ramachandra Children's and Dental Hospital, Guntur, Andhra Pradesh, India

Date of Submission17-Jan-2022
Date of Decision09-Mar-2022
Date of Acceptance29-Mar-2022
Date of Web Publication12-May-2022

Correspondence Address:
Dr. Sravani Kolla
13-7-1, 6th Lane Gunturuvarithota, Old Club Road, Guntur - 522 001, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcc.jpcc_9_22

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  Abstract 


Background: Dengue virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) share similar antigenic properties. In some studies, it has been shown that immunological memory/antibodies to dengue virus in endemic countries reduces the severity and spread of COVID-19. It is not known whether SARS-CoV-2 antibodies reduce or augment the severity of dengue viral infections. This study aims to evaluate the effects of SARS-CoV-2 antibodies on the outcomes of dengue infection in children.
Subjects and Methods: This was a retrospective observational study conducted at the pediatric emergency and intensive care units and wards of a tertiary care teaching hospital in Andhra Pradesh, India, between August and November 2021.
Results: About 400 children with dengue infection were admitted to our hospital, of which 96 children also had SARS-CoV-2 antibody titers estimated. In 50 (52.08%) of these 96 children, SARS-CoV-2 antibodies (IgG and/or IgM) were positive. In these 96 children, clinical severity and outcomes of dengue infection were compared between the two groups, i.e., with and without SARS-CoV-2 antibody positivity.
Conclusions: The present study provides preliminary evidence that outcome and severity of dengue infection in children are not affected by the SARS-CoV-2 antibody positivity.

Keywords: Antibody-dependent enhancement, cross-reactivity, dengue virus, severe acute respiratory syndrome coronavirus 2


How to cite this article:
Kolla S, Balleda L, Thimmapuram CS. Effect of severe acute respiratory syndrome coronavirus 2 antibodies on outcomes of dengue infected children: A retrospective observational study. J Pediatr Crit Care 2022;9:80-3

How to cite this URL:
Kolla S, Balleda L, Thimmapuram CS. Effect of severe acute respiratory syndrome coronavirus 2 antibodies on outcomes of dengue infected children: A retrospective observational study. J Pediatr Crit Care [serial online] 2022 [cited 2022 May 16];9:80-3. Available from: http://www.jpcc.org.in/text.asp?2022/9/3/80/345097




  Introduction Top


Dengue virus (DENV) is a positive, single-stranded RNA virus transmitted by mosquito species Aedes aegypti or Aedes albopictus.[1] The early clinical presentation of dengue and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses is quite similar, creating a serious challenge for health-care providers to differentiate between two diseases.[2],[3],[4] Furthermore, dengue and SARS-CoV-2 share antigenic similarities which can potentially alter these two mutual disease characteristics. In general, dengue viral infection is usually mild, but reinfection with the second type of strain may have a serious presentation. This phenomenon of antibody-dependent enhancement is due to the presence of nonneutralizing antibodies.[5],[6],[7],[8],[9] It is notable that DENV antibodies were also found to bind to receptor-binding domain amino acid residues that are crucial for interaction with the human angiotensin-converting enzyme-2 receptors, important for SARS CoV 2 entry into the cells.[7],[8],[9] It is possible that SARS-CoV-2 antibodies also can have a similar effect on altering dengue outcomes. Some studies showed that preexisting immunological memory to dengue infection may have a negative impact on transmission, severity, and pathogenesis of SARS-CoV-2 infections.[10] Hence, prior DENV exposure may be one of the reasons why dengue-endemic countries such as Japan, Singapore, and South Korea could flatten the curve of SARS-CoV-2 cumulative rise of infections over time more effectively than the countries where DENV is not endemic.[11],[12] Researchers from Brazil reported that the intensity of SARS CoV 2 epidemic, in terms of number, severity, and rapidity of the spread of infections, was lower in areas where a high prevalence of dengue fever was reported in the previous season.[11],[12],[13],[14] In contrast, Nicolete et al. and[4] Isabella et al.[12] have shown that prior dengue infection is associated with increased severity of SARS-CoV-2 infection. Till now, many of the above studies provided information regarding the effect of prior dengue infection on the outcomes of SARS-CoV-2 infection. Hence, we thought that it would be prudent to study the effect of prior SARS-CoV-2 infection as evidenced by antibody positivity on the outcomes of admitted dengue cases.


  Materials and Methods Top


This was a retrospective observational study conducted at the pediatric emergency and intensive care units and wards of a tertiary care teaching hospital in Andhra Pradesh, India, between August and November 2021. About 400 cases of dengue infection were admitted to our hospital during this period. The institutional ethics committee has approved the study (No.ECR/1110/Inst/AP/2018/RR-21). Written informed consent was waived as it was retrospective analysis of case records.

All children admitted to our hospital with dengue infection (either in the form of NS1 positive/NS1 with IgM positive/NS1 with IgG positive/NS1 with IgM and IgG positive/only IgM and IgG positive/only IgM positive) along with SARS CoV2 antibodies (IgM and/or IgG positivity) were included in the study. Children with isolated dengue IgG positivity were excluded from the study.

When the records of these cases were retrospectively and systematically analyzed, it was observed that 96 children had SARS-CoV-2 antibodies measured. Few had SARS-CoV-2 antibodies estimated before admission and the rest had SARS-CoV-2 antibodies estimated during the course of admission as we were in the midst of a COVID pandemic and multisystem inflammatory syndrome (MIS-C) was a differential at the time of admission. However, MIS-C was ruled out in all cases as they did not fulfill the WHO criteria of MIS-C.

The baseline demographic and clinical data were recorded. Details of supportive care (such as oxygen support), and hospital outcome (including duration of hospital stay/pediatric intensive care unit [PICU] stay/and mortality), were recorded and analyzed. The descriptive data were collected from the case records and electronic devices of laboratory and were entered into Microsoft Excel sheet.

The presentation of the categorical variables was done in the form of numbers and percentages (%). On the other hand, the quantitative data with non normal distribution was represented as median with 25th and 75th percentiles (interquartile range). The data normality was checked using Kolmogorov-Smirnov test. In the cases in which the data were not normal, we used nonparametric tests.

The following statistical tests were applied for the results:

  1. The association of the variables which were quantitative and not normally distributed in nature was analyzed using Mann–Whitney test (for two groups)
  2. The association of the variables which were qualitative in nature was analyzed using Chi-square test. If any cell had an expected value of <5, Fisher's exact test was used.


The data entry was done in the Microsoft Excel spreadsheet and the final analysis was done with the use of Statistical Package for the Social Sciences (SPSS) software, IBM Manufacturer, Chicago, Illinois, USA, version 21.0.

For statistical significance, P < 0.05 was considered statistically significant.


  Results Top


Demographic data of the study subjects showed a male preponderance. Fifty-nine (61.5%) patients were male and 37 (38.5%) patients were female. The mean age (years) of the study subjects was 6.15 ± 4.4 with median (25th–75th percentile) of 6 (2–9).

Distribution of dengue positivity showed that majority, i.e., 66 (68.7%), of the patients had only dengue NS1 positivity followed by dengue NS1 and IgM positivity in 18 (18.7%), only dengue IgM positivity in 6 (6.2%), dengue NS1 and IgG positivity in 3 (3.1%), and dengue IgG and IgM positivity in 2 (2.1%). Dengue NS1, IgG, and IgM were positive in 1 (1.04%) out of 96 patients [Table 1].
Table 1: Association of COVID antibodies with dengue

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SARS CoV 2 IgG antibodies were positive in 47 (48.96%)cases and IgM was positive in 9 (9.3%) cases. Altogether 50 (52.1%) cases were considered SARS-CoV-2 antibody positive (IgG and/or IgM positive). In 49 (51.04%) patients, SARS-CoV-2 IgG was negative. In majority of 87 (90.6%) patients, SARS-CoV-2 IgM was negative.

Out of the total of 96 Dengue cases included in the study, 52 (54.2%) patients had dengue without warning signs, 40 (41.7%) patients had dengue with warning signs, and 4 patients (4.2%) had severe dengue.

Outcomes showed that majority of 95 (98.9%) patients were discharged. One (1.04%) child expired. The mean value of duration of fever (days), duration of hospital stay (days), and duration of respiratory support (days) of study subjects were 3.92 ± 1.92, 6.26 ± 1.78, and 1.27 ± 1.98 with median (25th–75th percentile) of 4 (3–5), 6 (5–7), and 0 (0–3), respectively.

Distribution of positive SARS-CoV-2 antibodies was comparable between all the subgroups of dengue positivity (only NS1 positive, only IgM positive, NS1 and IgG positive, IgG and IgM positive, NS1 and IgM positive, and NS1, IgG, and IgM positive, 48.5% vs. 66.7% vs. 66.7% vs. 50% vs. 61.1% vs. 0%, respectively) (P = 0.802).

Distribution of severity of dengue was comparable between negative and positive SARS-CoV-2 antibodies (dengue with warning signs: 39.1% vs. 44%, respectively, dengue without warning signs: 58.7% vs. 50%, respectively, and severe dengue: 2.2% vs. 6%, respectively) (P = 0.566). No significant association was seen in outcome parameters such as duration of fever (days) (P = 0.662), duration of hospital stay (days) (P = 0.908), and duration of respiratory support (days) (P = 0.234) with SARS-CoV-2 antibodies. The median (25th–75th percentile) of duration of fever (days), duration of hospital stay (days), and duration of respiratory support (days) in negative SARS-CoV-2 antibodies were 4 (3–5), 6 (5–7), and 0 (0–2.25), respectively, and in positive SARS-CoV-2 antibodies was 4 (3–5), 6 (5–7), and 0 (0–3.75), respectively, with no significant association between them [Table 2].
Table 2: Association of outcome parameters with SARS-CoV-2 antibodies (nonparametric variables)

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  Discussion Top


In this retrospective observational study of 96 cases of dengue, it was observed that 52.1% had SARS-CoV-2 antibody (IgG and/or IgM) positivity. In a study by Ravikumar et al.,[2] about 34% of children had SARS-CoV-2 IgG antibody positivity. Our study showed a male preponderance, of which 59 (61.5%) patients were male and 37 (38.5%) patients were female, which was similar to Ravikumar et al.'s study in which males are 61%. The mean value of age (years) of study subjects was 6.15 ± 4.4 with median (25th–75th percentile) of 6 (2–9), whereas in the study by Ravikumar et al., the median age was 96 months.

The clinical outcomes including mortality, length of PICU stay, and length of hospital stay were not different between children with and without SARS-CoV-2 antibody positivity, which was similar to the study by Ravikumar et al.[2] The median length of hospital stay was 6 days in our study, which was comparable to the study by Ravikumar et al.[2] The incidence of dengue with warning signs was 41.7% and severe dengue was 4%, which were in contrast to the study by Ravikumar et al., in which dengue with warning signs and severe dengue were 32% and 68%, respectively.

The strength of the present study lies in its newer attempt to assess the effect of recent SARS-CoV-2 exposure on dengue infection in children in contrast to the earlier studies which studied the effect of prior dengue infection on SARS-CoV-2 infection. The present study explained that the severity and outcome of DENV infection in children is not affected by the recent/prior exposure to SARS-CoV-2 infection. However, the study has a limitation of small sample size.


  Conclusions Top


Prior SARS-CoV-2 exposure does not seem to affect the outcome of dengue infection. This may suggest that SARS-CoV-2 antibodies are probably not implicated in antigen–antibody-dependent enhancement of dengue infection. However, it is pertinent to understand the antigenic similarity and antibody response between the two viruses and their clinical relevance by further larger-scale studies.

Limitation

The limitations of this retrospective study are its sample size and a single-center study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Guabiraba R, Ryffel B. Dengue virus infection: Current concepts in immune mechanisms and lessons from murine models. Immunology 2014;141:143-56.   Back to cited text no. 1
    
2.
Lorenz C, Azevedo TS, Chiaravalloti Neto F. COVID 19 and dengue fever: A dangerous combination for the health system in Brazil. Travel Med Infect Dis 2020;35:101659.   Back to cited text no. 2
    
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Tiwari L, Shekhar S, Bansal A, Kumar P. COVID 19 with dengue shock syndrome in a child: Coinfection or cross reactivity? BMJ Case Rep 2020;13:e239315.   Back to cited text no. 3
    
4.
Lustig Y, Keler S, Kolodny R, Ben Tal N, Atias Varon D, Shlush E, et al. Potential antigenic cross reactivity between severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) and dengue viruses. Clin Infect Dis 2021;73:e2444-9.  Back to cited text no. 4
    
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Ravikumar N, Randhawa MS, Nallasamy K, Angurana SK, Kumar M, Mohi GK, et al. Impact of recent SARS CoV 2 infection on the course and severity of dengue in children: A prospective observational study from North India. Am J Trop Med Hyg 2021;105:751-5.   Back to cited text no. 6
    
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Nath H, Mallick A, Roy S, Sukla S, Biswas S. Computational modelling supports that dengue virus envelope antibodies can bind to SARS CoV 2 receptor binding sites: Is pre exposure to dengue virus protective against COVID 19 severity? Comput Struct Biotechnol J 2021;19:459 66.  Back to cited text no. 7
    
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Nicolete VC, Rodrigues PT, Johansen IC, Corder RM, Tonini J, Cardoso MA, et al. Interacting epidemics in Amazonian Brazil: Prior dengue infection associated with increased coronavirus disease 2019 (COVID 19) risk in a population based cohort study. Clin Infect Dis 2021;73:2045-54.   Back to cited text no. 8
    
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Mady BJ, Erbe DV, Kurane I, Fanger MW, Ennis FA. Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors. J Immunol 1991;147:3139-44.  Back to cited text no. 9
    
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Masyeni S, Santoso MS, Widyaningsih PD, Asmara DW, Nainu F, Harapan H, et al. Serological cross-reaction and coinfection of dengue and COVID-19 in Asia: Experience from Indonesia. Int J Infect Dis 2021;102:152-4.  Back to cited text no. 10
    
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Silvestre OM, Costa LR, Lopes BV, Barbosa MR, Botelho KK, Albuquerque KL, et al. Previous dengue infection and mortality in coronavirus disease 2019 (COVID-19). Clin Infect Dis 2021;73:e1219-21.  Back to cited text no. 11
    
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Isabella M.S NT, Juliana Lott de Carvalho, LuizCláudio et al. Clinical and biochemical parameters of COVID-19 patients with prior or active dengue fever, Acta Tropica.2021;214:105782. Doi:10.1016/j.actatropica.2020.10578. PMID-33259817.  Back to cited text no. 12
    
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Tsheten T, Clements AC, Gray DJ, Adhikary RK, Wangdi K. Clinical features and outcomes of COVID-19 and dengue co-infection: A systematic review. BMC Infect Dis 2021;21:729.  Back to cited text no. 13
    
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Biswas, Subhajit & Sukla, Soumi. (2020). COVID-19 Virus Infection and Transmission are Observably Less in Highly Dengue-Endemic Countries: Is Pre-Exposure to Dengue Virus Protective Against COVID-19 Severity and Mortality? Will the Reverse Scenario Be True?. Clinical and Experimental Investigations. 1-5. 10.31487/j.CEI.2020.02.05.  Back to cited text no. 14
    



 
 
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