We present an ensemble forecast for Wave-3 of COVID-19 in the state of Karnataka, India, using the IISc Population Balance Model for infectious disease spread. The reported data of confirmed, recovered, and deceased cases in Karnataka from 1 July 2020 to 4 July 2021 is utilized to tune the models parameters, and an ensemble forecast is done from 5 July 2021 to 30 June 2022. The ensemble is built with 972 members by varying seven critical parameters that quantify the uncertainty in the spread dynamics (antibody waning, viral mutation) and interventions (pharmaceutical, non-pharmaceutical). The probability of Wave-3, the peak date distribution, and the peak caseload distribution are estimated from the ensemble forecast. Our analysis shows that the most significant causal factors are compliance to Covid-appropriate behavior, daily vaccination rate, and the immune escape new variant emergence-time. These causal factors determine when and how severe the Wave-3 of COVID-19 would be in Karnataka. We observe that when compliance to Covid-Appropriate Behavior is good (i.e., lockdown-like compliance), the emergence of new immune-escape variants beyond Sep 21 is unlikely to induce a new wave. A new wave is inevitable when compliance to Covid-Appropriate Behavior is only partial. Increasing the daily vaccination rates reduces the peak active caseload at Wave-3. Consequently, the hospitalization, ICU, and Oxygen requirements also decrease. Compared to Wave-2, the ensemble forecast indicates that the number of daily confirmed cases of children (0-17 years) at Wave-3s peak could be seven times more on average. Our results provide insights to plan science-informed policy interventions and public health response.
