Did COVID-19 or COVID-19 vaccines influence the patterns of Dengue in 2021: An exploratory analysis of two observational studies from North India (preprint)

Background Dengue which is endemic in India and has been occurring for decades apparently witnessed a rise in disease burden in 2021 in specific regions of the nation. We aim to explore less studied risk factors of Dengue occurrence and severity in the post-COVID-19 and post-COVID-19 vaccination era. Methods This was an exploratory analysis involving participants from two prior observational studies conducted during the period of Feb 2021-April 2022 in a tertiary hospital in North India. Healthcare workers constituted the majority of study participants. Individuals were stratified into five groups based on COVID-19 infection and timing of vaccination: CovidNoVaccine (CNV), VaccineNoCOVID (VNC), CovidAfterVaccine (CAV), VaccineAfterCOVID (VAC) and NoVaccineNoCovid (NVNC) groups. The occurrence of lab-confirmed Dengue and severe forms of Dengue were the main outcomes of interest. We tried to predict determinants of Dengue occurrence and severity with a particular focus on COVID-19 history and vaccination status. Results A total of 1520 vaccinated individuals and 181 unvaccinated individuals were included. Of these 1701 participants, symptomatic Dengue occurred in 133 (7.8%) and was of 'severe' category in 42 (31.6%). Individuals with a history of COVID-19 in 2020 had 2 times higher odds of developing symptomatic Dengue. The VAC group had 3.6, 2- and 1.9 times higher odds of developing Dengue than the NVNC, VNC, and CAV groups. The severity of dengue was not affected by COVID-19 or COVID-19 vaccination. Conclusions COVID-19 may enhance the risk of developing symptomatic dengue. Future research dealing with long COVID should explore the propensity of COVID-19 victims towards symptomatic forms of other viral illnesses. Individuals receiving the COVID-19 vaccine after recovering from COVID-19 particularly seem to be at greater risk of symptomatic dengue and need long-term watchfulness. Possible mechanisms, such as antibody-mediated enhancement or T-cell dysfunction, should be investigated in COVID-19-recovered and vaccinated individuals. Further large-scale, multicentric, robust studies with a better enrolment of unvaccinated people will help understand the interplay of factors involved in COVID-19 and Dengue.

Persistent health issues, adverse events of significant concern, and effectiveness of COVID-19 vaccination- findings from a real-world cohort study of healthcare workers in north India (preprint)

Background: There is paucity of real-world data on COVID-19 vaccine effectiveness and safety from cohort designs. The current study aimed to evaluate vaccine performance during second wave in India. It also aimed to determine adverse events of significant concern (AESCs), and to ascertain the effect of vaccination on persistent health issues in individuals post COVID-19. Methods: A cohort study was conducted from July-2021 to December-2021 in a tertiary hospital of north India. The primary outcome was vaccine-effectiveness against COVID-19. Secondary outcomes were AESCs, and persistent health issues in those receiving vaccine. Regression analyses were performed to determine risk factors. Results: In 2760 healthcare workers (HCWs) included, 1033 COVID-19 events were reported. Around 6-17% vaccine effectiveness was observed against COVID-19 occurrence. One dose-recipients were at 1.6-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.5-times increased risk of moderate-severe COVID-19. AESCs were observed in 1.3% including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times and those receiving vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusion: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. Relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. Independent protection of prior SARS-CoV-2 infection was high and persistent health issues were common in individuals receiving vaccine post COVID-19. Recommendations of vaccinating those recovered from COVID-19 need further studies.

Patterns and predictors of COVID-19 occurrence and severity in vaccinated priority groups (preprint)

Background: Varying protection rates have been observed with approved COVID-19 vaccines post-approval, in various real-world studies. However, little data exists on the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The aim of the present study is to describe the patterns of presentation of COVID-19 in vaccinated individuals, and to determine the predictors of occurrence of COVID-19 and the predictors of severity in the vaccinated. Methods: : The study is a part of a prospective observational study ongoing since February 2021 in a tertiary teaching and research hospital of northern India. Individuals recruited in this study belong to a high-risk group comprising health care workers and elderly. COVISHIELD, based on ChAdOx1 nCoV-19 platform was the vaccine received by the participants based on policy on allocation.Primary outcomes of the study are the short term and long-term adverse events following immunization (AEFI) with COVID-19 vaccines. Secondary outcomes include the rates of occurrence of COVID-19 and severity of COVID-19. Data on these have been already reported. The clinical presentation, typical and atypical manifestations, time to symptomatic recovery and patterns of post-COVID-19 complaints were analysed in the current study. Logistic regression analysis was performed to predict the risk factors of occurrence of COVID-19 in the vaccinated and the determinants of severe forms of the disease in this group. Findings: 1500 individuals completed at least two month follow up. Of these, 418 developed laboratory confirmed or suspected COVID-19. Fever was the commonest symptom (72%), followed by features of rhinitis (41%) and cough (34%). Nearly 12% individuals had only one symptom or none. Cardiovascular involvement was seen in more than 2% of affected. Time to symptomatic recovery varied from 1-75 days and 11% had post COVID-19 complaints at two month follow up, most common being generalized weakness. Results of regression analysis showed 1.6 times higher odds of contracting the disease in females and young individuals < 40 years of age (P<0.001). Overweight individuals and those receiving only one dose were at 1.4 times and 3 times higher odds of contracting COVID-19 compared to those with normal body mass index and those who were fully vaccinated. Individuals receiving two doses at a gap of < 30 days were at 7 times higher odds of disease acquisition compared to those receiving the second dose at an extended gap of > 60 days (P=0.01).With respect to severity, males and those receiving only one dose each had 3 times higher odds of suffering from moderate to severe COVID-19 compared to females and fully vaccinated. Persons with pre-existing lung disease, such as asthma had 6 times higher odds of suffering from moderate to severe COVID-19 (P=0.024). No association with the occurrence or severity of disease was observed with any other co-morbidity or the use of renin-angiotensin-aldosterone system (RAAS) blockers. Interpretation Sex wise differences exist with respect to occurrence and severity of COVID-19. Two doses of vaccine, compared to one dose provide considerable protection against occurrence as well as severity. Full vaccination with extended dosing interval should be the optimal strategy and should be carried out when the community burden of cases is negligible. Future studies are needed to explore the sex wise differences in the propensity and severity of COVID-19. Further, the risk association of asthma phenotypes with COVID-19 needs to be investigated. Funding: The study received no funding support