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Two hundred days after the first confirmed case of COVID-19 in Brazil, the epidemic has rapidly spread in metropolitan areas and advanced throughout the countryside. We followed the temporal epidemic pattern at São Paulo State, the most populous of the country, the first to have a confirmed case of COVID-19, and the one with the most significant number of cases until now. We analysed the number of new cases per day in each regional health department and calculated the effective reproduction number (Rt) over time. Social distance measures, along with improvement in testing and isolating positive cases, general population mask-wearing and standard health security protocols for essential and non-essential activities, were adopted and impacted on slowing down epidemic velocity but were insufficient to stop transmission. Background and epidemiology Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Brazil on 25 February 2020, in São Paulo [1]. The most populous city of Latin America was the route for COVID-19 importation, mainly from the USA and Italy [2]. It took 17 days for Brazil to reach a hundred cases, mainly reported in the capitals highly connected by airports and with an intensive flux of people. Two hundred days after the first confirmed case, the epidemic rapidly spreads across the country, and the disease advances through the interior. São Paulo implemented state-wide quarantine measures quite early in the epidemic course. On 24 March, the government adopted a social distance recommendation for all people associated with closing trade and non-essential services. The decree suggested that people’s movement should be limited to the immediate needs for food and health care. Despite the enforces, adherence to safety protocols was more significant in the capital, and COVID-19 took the inner route in São Paulo State [3]. Two patterns of disease dispersion were described by Fortaleza et al. [4]: one by contiguity, in which the virus spreads through areas of conurbation, and another hierarchical (long-distance spread through elementary spatial structures, such as highways, to cities with several degrees of connectivity). São Paulo State is divided into 17 health departments with respect to epidemiological control, each one represented by a major city: Araraquara, Araçatuba, Baixada Santista, Barretos, Bauru, Campinas, Franca, São Paulo Metropolitan Area, Marília, Piracicaba, Presidente Prudente, Registro, Ribeirão Preto, São João da Boa Vista, São José do Rio Preto, Sorocaba and Taubaté. COVID-19 was introduced in different moments and behaved in different ways in each one of these Regional Health Departments (DRS, in Portuguese). We aimed to study COVID-19 advance in all these regions by analysing new confirmed cases per day (after the first case of COVID-19 in Brazil) and calculating the effective reproduction number (Rt) of SARS-CoV-2 over time. Also, daily new cases of Severe Acute Respiratory Illness (SARI) and its Rt number were estimated as an alternative way to follow the temporal evolution of the disease in a country still struggling to increase testing capacity [5]. Since 27 May, São Paulo State adopted a plan of quarantine measures (‘Plano São Paulo’), which can be more restrictive or more flexible, considering the growth rate of COVID-19 cases and deaths, and bed occupancy rates in each DRS. All cities belonging to a DRS are ruled by the same quarantine measures, which were called phases. Phase 1 (red phase) is considered a contamination phase, in which the rates of spread of the disease are high and, the capacity of the health system is close to its limit, with permission only for essential services. Phase 2 (orange phase) is considered an attention phase, with the possibility of some services opening. For commerce, limit to maximum occupancy 20% of the location’s capacity, with reduced hours: 4 h in a row on all days of the week or 6 h in a row on 4 days of the week, always adopting standard and sector-specific protocols. Food courts are still banned in this phase. Phase 3 (yellow) is considered a controlled phase, with some flexibilisation. For example, commerce may open with maximum occupancy limited to 40% of total capacity and reduced hours (8 h). Finally, phase 4 (green), a partial opening phase, in which all services are allowed to open, respecting the limit of 60% of capacity and maintaining all specific protocols. Bars, restaurants, beauty salons and barbershops will only be open from phases 3 and 4, yellow and green.