Impact of previous SARS-CoV-2 infection on the rate of mortality in dengue. A preliminary report from Pakistan

Dear Editor,

An interesting article recently published in this journal offers an insightful overview of the COVID-19 and alarming dengue outbreak in Pakistan [1]. To this aim, an elegant parallel is also made with dengue mortality in patients previously exposed to SARS-CoV-2 infection.

The outbreak of SARS-CoV-2 spread rapidly across the globe resulting in unprecedented public health problems worldwide. As of 23 November 2021, over 258 million cases and over 5 million deaths have been reported around the world. Similarly, in Pakistan, the toll of confirmed COVID-19 cases reached 12,82,510 including 28,668 deaths since 26 February 2020 [2].

On the other hand, the incidence of dengue has grown dramatically around the world in recent decades. It is estimated that 390 million dengue infections and 40,000 related deaths occurred per year with 70% of the world's dengue burden being in Asia. Out of 390 million dengue cases, only 24% manifest clinical symptoms, and the other 76% remain asymptomatic. The total number of dengue cases reported to WHO increased over 10 fold from 0.5 million cases in 2000 to over 5.2 million in 2019 [3]. In 2021, 1 316 518 dengue cases have been reported, the majority of the cases are from Brazil, India, Vietnam, Peru Philippines, Pakistan, Bangladesh, Nepal and Colombia [4].

Unfortunately, dengue is endemic in Pakistan since 1994, when the first laboratory-confirmed dengue outbreak occurred in Karachi city of Sindh province. From 1994 to 2009 localized dengue outbreaks with 8549 cases including 215 deaths were reported in Karachi, Pakistan. During the last decade 2010–2020, yearly outbreak of dengue has more frequent and expanded to every corner of the country with 144,855 cases including 625 deaths. In Pakistan the largest ever dengue outbreak was reported in 2019, infecting over 52,485 individuals with 75 related deaths [5].

During the current year, sporadic dengue cases were detected since February 2021. However, this dengue outbreak gets intensified during the post moon soon season from September to November 2021. As of 23 November 2021, a total of 2,36,773 suspected and 50,120 confirmed dengue cases including 227 deaths have been reported in Pakistan. 50% (25,000/50,120) of the total cases were reported from Punjab province. Province-wide distribution of dengue cases showed that over 85% of total cases reported by each province are from the highly populous cities such as Lahore, Karachi, Peshawar, Quetta, Islamabad, and Muzaffarabad, which are considered as the hotspot for dengue outbreaks for the last many years. It is speculated that the actual number of dengue cases and deaths might be high than reported as most dengue cases remain asymptomatic and become a source of infection for the community. According to the current data, the rate of mortality due to dengue is very high as compared to previous dengue outbreaks. It is already reported that the dengue infection provides the protective immunity against the same serotype and increases the severity of the infection if infected by the other serotype due to the antibodies dependent enhancement (ADE). We closely observed and reviewed the data and recent lab results of dengue virus serotypes circulating in Pakistan. Previous and current serotyping data showed that the dengue virus serotype-2 (DENV-2) is circulating as a dominant strain in Pakistan since 2017 [5,6,7]. During the current dengue outbreak over 500 samples covering almost all regions of the country were screened for the identification of dengue serotypes at the department of Virology, National Institute of Health Islamabad and DENV-2 was detected from all positive samples (NIH unpublished data 2021). In the presence of a single serotype from the last five years, the unprecedented rise (33%, 75/227) in dengue-related deaths in 2021 as compared to 2019 showed that the previous COVID-19 infection increases the risk of severe dengue and dengue-related deaths due to the ADE, Fig. 1 . We thoroughly reviewed the hospital medical records of deceased dengue patients and dengue NS1 positive lab reports were available for all 201 patients. However, 71% (162/227) of patients who died due to dengue had a history of pre-exposure to SARS-CoV-2 infection. COVID-19 PCR and IgG positive reports were found in the hospital records for 59 patients; however, only PCR positive reports were available for 103 patients. We are unable to trace the COVID-19 PCR or serology results for the other 65 patients who died due to dengue virus infection. Out of total deceased dengue patients, 63% (143/227) were male and the other 37% (84/227) were female patients. Most deceased dengue patients belonged to the 35–75 year of age group. The cross-reactivity of COVID-19 and dengue antibodies has already been reported [8]. In our previous study, we have already reported the co-infection of dengue and COVID-19 with unfavorable outcomes. A recently published study in the journal of clinical infectious diseases also reported that the previous dengue infection increases the risk of severe COVID-19 due to the cross-reactivity of non-neutralizing antibodies [9]. If the previous infection of dengue increases the risk of severe COVID-19 and the previous exposure to covid-19 ultimately increases the risk of severe dengue as indicated by the results of the present study. Both COVID-19 and dengue are significant public health problems, especially in dengue-endemic countries. The present study explored the preliminary observational evidence that the previous COVID-19 infection might increase the risk of mortality due to dengue virus infection. The Bidirectional impact of ADE in COVID-19 versus dengue is a growing concern. This phenomenon is enormously important not only for the understanding of viral pathogenesis but also for developing antiviral strategies such as vaccines for COVID-19 and dengue. Rigorous research work on deep cellular and immunological aspects from dengue-endemic countries is needed to further elucidate the effect of antibodies cross-reactivity in patients having pre or post exposure to COVID-19 and dengue

Fig. 1.

Dengue reported case counts and deaths from 2012 to 2021.

Declaration of Competing Interest

The authors declared that there is no conflict of interest.