Modelling the unexpected dynamics of COVID-19 in Manaus, Brazil.

In late March 2020, SARS-CoV-2 arrived in Manaus, Brazil, and rapidly developed into a large-scale epidemic that collapsed the local health system and resulted in extreme death rates. Several key studies reported that ∼76% of residents of Manaus were infected (attack rate AR≃76%) by October 2020, suggesting protective herd immunity had been reached. Despite this, an unexpected second wave of COVID-19 struck again in November and proved to be larger than the first, creating a catastrophe for the unprepared population. It has been suggested that this could be possible if the second wave was driven by reinfections. However, it is widely reported that reinfections were at a low rate (before the emergence of Omicron), and reinfections tend to be mild. Here, we use novel methods to model the epidemic from mortality data without considering reinfection-caused deaths and evaluate the impact of interventions to explain why the second wave appeared. The method fits a "flexible" reproductive number R0(t) that changes over the epidemic, and it is demonstrated that the method can successfully reconstruct R0(t) from simulated data. For Manaus, the method finds AR≃34% by October 2020 for the first wave, which is far less than required for herd immunity yet in-line with seroprevalence estimates. The work is complemented by a two-strain model. Using genomic data, the model estimates transmissibility of the new P.1 virus lineage as 1.9 times higher than that of the non-P.1. Moreover, an age class model variant that considers the high mortality rates of older adults show very similar results. These models thus provide a reasonable explanation for the two-wave dynamics in Manaus without the need to rely on large reinfection rates, which until now have only been found in negligible to moderate numbers in recent surveillance efforts.

Modelling of Waning of Immunity and Reinfection Induced Antibody Boosting of SARS-CoV-2 in Manaus, Brazil.

It was reported that the Brazilian city, Manaus, likely exceeded the herd immunity threshold (presumably 60-70%) in November 2020 after the first wave of COVID-19, based on the serological data of a routine blood donor. However, a second wave started in November 2020, when an even higher magnitude of deaths hit the city. The arrival of the second wave coincided with the emergence of the Gamma (P.1) variant of SARS-CoV-2, with higher transmissibility, a younger age profile of cases, and a higher hospitalization rate. Prete et al. (2020 MedRxiv 21256644) found that 8 to 33 of 238 (3.4-13.9%) repeated blood donors likely were infected twice in Manaus between March 2020 and March 2021. It is unclear how this finding can be used to explain the second wave. We propose a simple model which allows reinfection to explain the two-wave pattern in Manaus. We find that the two waves with 30% and 40% infection attack rates, respectively, and a reinfection ratio at 3.4-13.9%, can explain the two waves well. We argue that the second wave was likely because the city had not exceeded the herd immunity level after the first wave. The reinfection likely played a weak role in causing the two waves.

New estimates of the Zika virus epidemic attack rate in Northeastern Brazil from 2015 to 2016: A modelling analysis based on Guillain-Barré Syndrome (GBS) surveillance data.

BACKGROUND: Between January 2015 and August 2016, two epidemic waves of Zika virus (ZIKV) disease swept the Northeastern (NE) region of Brazil. As a result, two waves of Guillain-Barré Syndrome (GBS) were observed concurrently. The mandatory reporting of ZIKV disease began region-wide in February 2016, and it is believed that ZIKV cases were significantly under-reported before that. The changing reporting rate has made it difficult to estimate the ZIKV infection attack rate, and studies in the literature vary widely from 17% to > 50%. The same applies to other key epidemiological parameters. In contrast, the diagnosis and reporting of GBS cases were reasonably reliable given the severity and easy recognition of the disease symptoms. In this paper, we aim to estimate the real number of ZIKV cases (i.e., the infection attack rate) and their dynamics in time, by scaling up from GBS surveillance data in NE Brazil. METHODOLOGY: A mathematical compartmental model is constructed that makes it possible to infer the true epidemic dynamics of ZIKV cases based on surveillance data of excess GBS cases. The model includes the possibility that asymptomatic ZIKV cases are infectious. The model is fitted to the GBS surveillance data and the key epidemiological parameters are inferred by using a plug-and-play likelihood-based estimation. We make use of regional weather data to determine possible climate-driven impacts on the reproductive number [Formula: see text], and to infer the true ZIKV epidemic dynamics. FINDINGS AND CONCLUSIONS: The GBS surveillance data can be used to study ZIKV epidemics and may be appropriate when ZIKV reporting rates are not well understood. The overall infection attack rate (IAR) of ZIKV is estimated to be 24.1% (95% confidence interval: 17.1%-29.3%) of the population. By examining various asymptomatic scenarios, the IAR is likely to be lower than 33% over the two ZIKV waves. The risk rate from symptomatic ZIKV infection to develop GBS was estimated as ρ = 0.0061% (95% CI: 0.0050%-0.0086%) which is significantly less than current estimates. We found a positive association between local temperature and the basic reproduction number, [Formula: see text]. Our analysis revealed that asymptomatic infections affect the estimation of ZIKV epidemics and need to also be carefully considered in related modelling studies. According to the estimated effective reproduction number and population wide susceptibility, we comment that a ZIKV outbreak would be unlikely in NE Brazil in the near future.

Simple framework for real-time forecast in a data-limited situation: the Zika virus (ZIKV) outbreaks in Brazil from 2015 to 2016 as an example.

BACKGROUND: In 2015-2016, Zika virus (ZIKV) caused serious epidemics in Brazil. The key epidemiological parameters and spatial heterogeneity of ZIKV epidemics in different states in Brazil remain unclear. Early prediction of the final epidemic (or outbreak) size for ZIKV outbreaks is crucial for public health decision-making and mitigation planning. We investigated the spatial heterogeneity in the epidemiological features of ZIKV across eight different Brazilian states by using simple non-linear growth models. RESULTS: We fitted three different models to the weekly reported ZIKV cases in eight different states and obtained an R2 larger than 0.995. The estimated average values of basic reproduction numbers from different states varied from 2.07 to 3.41, with a mean of 2.77. The estimated turning points of the epidemics also varied across different states. The estimation of turning points nevertheless is stable and real-time. The forecast of the final epidemic size (attack rate) is reasonably accurate, shortly after the turning point. The knowledge of the epidemic turning point is crucial for accurate real-time projection of the outbreak. CONCLUSIONS: Our simple models fitted the epidemic reasonably well and thus revealed the spatial heterogeneity in the epidemiological features across Brazilian states. The knowledge of the epidemic turning point is crucial for real-time projection of the outbreak size. Our real-time estimation framework is able to yield a reliable prediction of the final epidemic size.