key: cord-0714178-otmaq09i authors: El‐Qushayri, Amr Ehab; Kamel, Ahmed Mostafa Ahmed; Reda, Abdullah; Ghozy, Sherief title: Does dengue and COVID‐19 co‐infection have worse outcomes? A systematic review of current evidence date: 2022-02-25 journal: Rev Med Virol DOI: 10.1002/rmv.2339 sha: 53993130e7d5e707355cb88dfde1165c0ba30b1f doc_id: 714178 cord_uid: otmaq09i In dengue‐endemic regions, the co‐infection with SARS‐CoV‐2 and dengue is a significant health concern. Therefore, we performed a literature search for relevant papers in seven databases on 26 Spetember 2021. Out of 24 articles, the mortality rate and intensive care unit (ICU) admission were 19.1% and 7.8%, respectively. The mean hospital stay was 11.4 days. In addition, we identified two pregnancies with dengue and COVID‐19 co‐infection; one ended with premature rupture of membrane and intrauterine growth restriction fetus, while the other one ended with maternal mortality and intrauterine fetal death. COVID‐19 and dengue co‐infection had worse outcomes regarding mortality rates, ICU admission, and prolonged hospital stay. Thus, wise‐decision management approaches should be adequately offered to these patients to enhance their outcomes. Establishing an early diagnosis might be the answer to reducing the estimated significant burden of these conditions. conducted a systematic search following the recommendations of PRISMA's checklist to detect our included studies. We used the search term '(Dengue Fever OR Dengue) AND (COVID-19 OR COVID 19 OR novel coronavirus OR SARS CoV 2)' through seven databases including PubMed, Google Scholar, Scopus, Web of Science (ISI), Virtual Health Library, The New York Academy of Medicine, and System for information on Grey Literature in Europe. Our search results were collected using EndNote software, where duplications were removed. Subsequently, we moved the results to Microsoft Excel sheets, and two phases of title and abstract screening followed by full-text screening were done. Two authors screened the results independently, and we included the study upon their agreement. A senior reviewer was added to solve any discrepancy in case of disagreement. We included all articles that reported dengue and COVID-19 co-infection and excluded reviews, conference papers, and no available full texts. In addition, a manual search was performed through references of included articles and relevant articles in Google Scholar and PubMed ( Figure 1 ). We made an excel sheet containing our outcomes of interest. The characteristics of each study included (study design, sample size, country, and sex) while the patients' outcomes were (mortality, intensive care unit (ICU) admission, hospital stay length, obstetric and foetal outcomes). We calculated the prevalence of mortality and ICU admission by dividing the number of deaths and ICU admissions, respectively, by the total number of cases. The extraction was done by three reviewers separately, and the final results were considered upon consensus. A senior author was added for the discussion if needed. Moreover, we did a quality assessment for our included papers using the Joanna Briggs Institute Critical Appraisal tool for F I G U R E 1 Flow diagram or the study process 2 of 7 -EL-QUSHAYRI ET AL. case report papers and The National Institute of Health tool for cohort studies (Table S1 and S2). After screening 1318 papers, 47 papers were eligible for another phase of full text screening. Out of these, we included 18 papers together with additional 6 papers from manual search trials. Finally, we had 24 articles with a sample size of 89 patients with dengue and COVID-19 co-infection with a male prevalence of 63% (Table 1, Figure 1 ). Regarding study design, there were 22 case reports and two retrospective cohort studies. In terms of countries of patients, Peru, followed by Argentina, Saudi Arabia, and India, had the highest numbers of dengue-COVID-19 co-infected patients (Figure 2 ). Out of 89 cases identified with dengue and COVID-19 co-infection, 17 patients passed away, with a prevalence of 19.1%. In addition, the mortality rates were higher among males than females, with a prevalence of 10.1% and 9%, respectively. Seven cases needed ICU admission, assuming a prevalence of 7.8%. Twenty-one papers reported the hospital stay duration. The mean hospital stay for the included 37 patients was 11.4 days. We identified two pregnancies with dengue and COVID-19 co-infection. One ended with premature rupture of membrane (PROM) and intrauterine growth restriction (IUGR) foetus, while the other one ended with maternal mortality and intrauterine foetal death (IUFD). In the present systematic review, we mainly aimed to determine the clinical outcomes of patients suffering from dengue and COVID-19 co-infection. Our results indicated the high mortality rate among these patients (19.1%), based on cumulative evidence from relevant studies. It should be noted that this rate is remarkably higher than the estimated global rates for dengue and COVID-19 patients (1.3% and 2.04%, respectively). 8, 9 Moreover, we noted that the prevalence of co-infection and mortality was higher among males. This is consistent with previous dengue investigations, which indicated that the prevalence of dengue infection is higher among males. [10] [11] [12] [13] [14] Many reasons have been proposed for these differences, including using fully covered dresses by females, potential differences in healthcare services, and prioritising provisions of male individuals in societies where dengue is endemic. 15, 16 To the best of our knowledge, advanced age is considered one of the major risk factors in patients with dengue fever or COVID-19 infections. 17, 18 In our study, two patients from two case reports who experienced death event had an age of 59 and 60 years. 19, 20 Moreover, in the case series of Parra and colleagues, mortality rate was 28% in patients with dengue and COVID-19 co-infection whose median age was 55.5 years. 21 Due to the limited sample size in our study, we can not confirm the role of age in predicting mortality from dengue and COVID-19 co-infection. Therefore, more studies with bigger sample size and controlling of other confouders are needed for studying this association. Our results also show a high rate of ICU admissions secondary to COVID-19 and dengue infection, being 7.8%. However, it should be noted that this rate is lower than the estimated one for COVID-19 patients, being 9.8%. 22 This might be attributed to the different population characteristics and quality of care offered to both populations. The rate of patients requiring ICU admission secondary to severe dengue is also high. Previous dengue-related studies indicated that the mortality rate among patients admitted to the ICU secondary to severe dengue manifestations might be up to 23.1%. [23] [24] [25] [26] Such differences are usually attributed to the method of defining severe disease in these patients and the degree of severity of included participants, as reported among these studies. We furtherly found that our population had a mean hospital stay of 11.4 days. In the literature, the estimated median hospital stay for individual COVID-19 and dengue populations are 5 and 6 days, respectively. 27, 28 Previous dengue studies reported that hospital stay was remarkably longer among infants than children and adults. This has been attributed to the frequency of complications, which might affect this age group at a potentially higher rate secondary to the infection. 15, 29, 30 Many factors can contribute to severe COVID-19, including co-infection. [31] [32] [33] [34] [35] [36] The current literature reveals a solid association between COVID-19 and co-infection with different viruses and bacteria. As a result, these patients usually have severe outcomes due to remarkable deterioration in their health status. 31 A previous meta-analysis reported that the prevalence of bacterial co-infection with COVID-19 was 5.1%, while secondary infection accounted for 13.1%. Moreover, it has been shown that the rate of ICU admissions was significantly associated with bacterial infections among COVID-19 patients. 37 In addition, it is widely known that COVID-19 is associated with a high rate of complications that are usually lifethreatening. [38] [39] [40] Many previous studies also showed that among patients with severe dengue infection, up to 55.9% suffered from a concurrent bacterial infection. 23, 26 Dengue infection might also lead EL-QUSHAYRI ET AL. to serious morbidities such as dengue shock syndrome and dengue haemorrhagic fever, [41] [42] [43] [44] [45] [46] contributing to the estimated high rates of mortality and ICU admissions in the current study. Regarding obstetric and foetal outcomes, we only found two pregnancies with COVID-19 and dengue co-infection occurred, both of which were complicated; one with PROM and IUGR and the other with maternal mortality and IUFD. Evidence from various studies in the literature indicates that neonatal dengue infection is attributed to vertical transmission of the virus from an affected mother. Based on these investigations, the diagnosis of dengue in these neonates was related to maternal dengue infection (occurring amid delivery by 10 days). [47] [48] [49] Many relevant studies also demonstrated that dengue infection in this population is usually associated with premature birth, stillbirth, or low birth weight. 48, [50] [51] [52] [53] On the other hand, some studies suggested that vertical transmission of protective antibodies from infected mothers to their infants during placental transfer might reduce the severity of the disease and enhance the outcomes. 28 However, it has been demonstrated that these antibodies are agedependent and usually decrease with advancing age. 54 endemic is also encouraged, owing to the remarkable burden over these populations. 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Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. World Health Organization Dengue in pregnancy The global burden of dengue: an analysis from the Global Burden of Disease Study We would like to thank Abdelaziz Abdelaal (Faculty of Medicine, Tanta University, Tanta, Egypt) for his efforts and help in the current work. The authors received no funding for this study. None. Amr Ehab El-Qushayri was responsible for the idea and the study design. All authors shared in screening, extraction, and writing of the full text. Sherief Ghozy supervised all steps, and all authors approved the final version before submission. The data that supports the findings of this study are available from the corresponding author upon reasonable request.