Vaccine effectiveness of CoronaVac against symptomatic and severe COVID-19 among children in Brazil during the Omicron period (preprint)

Compared to previous variants, the SARS-CoV-2 B.1.1.529 (Omicron) variant has relatively high infection rates, including among children. Even though severe COVID-19 in children is rare, this group is susceptible to the multisystem inflammatory syndrome in Children (MIS-C), long-COVID and downstream effects of COVID-19, including social isolation and education disruption. There is evidence that vaccination with an mRNA vaccine offers protection against infection and severe forms of COVID-19 for children. However, data on the effectiveness of inactivated virus vaccine, the most used platform worldwide, is scarce during the Omicron period. In Brazil, children between 6 to 11 years are eligible to receive the CoronaVac vaccine. Using a national linked database from January 21, 2022, up to April 19, 2022, during the Omicron dominant period in Brazil, we conducted a test-negative design with 194,258 tests to assess CoronaVac effectiveness against infection and severe (hospitalisation or death) outcomes among children aged 6 to 11 years. The estimated VE for symptomatic infection was 35.0% (95% CI 27.7–41.5) at 0–13 days and 41.5% (95% CI: 34.4–47.7) at ≥ 14 days post-second dose. For severe outcomes (hospitalisation or death) VE was 69.2% (95% CI: 11.7–93.6) at 0–13 days and 63.5% (95% CI: 5.8–90.0). Two doses of CoronaVac in children during the Omicron period showed low levels of protection against symptomatic infection, and modest levels against severe illness.

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals (preprint)

There are large differences in the shape and size of regional SARS-CoV-2 epidemics in Brazil. Here we tested monthly blood donation samples for IgG antibodies from March 2020 to March 2021 in eight of Brazil’s most populous cities. There was large variation in the inferred attack rate adjusted for seroreversion across cities, and seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate differed between cities and consistently increased with age. The infection hospitalisation rate (IHR) increased significantly during the gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system’s collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43–3.53). These results demonstrate large heterogeneity in epidemic spread and highlight the utility of blood donor serosurveillance to monitor SARS-CoV-2 epidemics.

Effectiveness of the CoronaVac Vaccine in Prevention of Symptomatic and Progression to Severe COVID-19 in Pregnant Women in Brazil (preprint)

Background: The effectiveness of Covid-19 inactivated vaccines in pregnant women is unknown. We estimated vaccine effectiveness (VE) of CoronaVac against symptomatic and severe Covid-19 and in preventing progression from symptomatic to severe Covid-19 in pregnant women in Brazil. Methods: We conducted a test-negative design study in all pregnant women aged 18 to 49 years in Brazil, linking records of negative and positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) tests to national vaccination records. We also linked records of test positive cases with notification of severe, hospitalized or fatal Covid-19. Using logistic regression, we estimated adjusted odds and VE against symptomatic Covid-19 by comparing vaccine status in test positive (confirmed cases) to that in subjects with a negative test result. We also calculated the odds/VE against progression by comparing vaccine status in symptomatic cases to that in severe Covid-19 cases. Results: Of 19838 tested pregnant women, 7424 (37.4%) tested positive for Covid-19 and 588 (7.9%) had severe disease. Only 83% of pregnant women who received a first dose of CoronaVac completed the vaccination scheme. A single dose of the CoronaVac vaccine was not effective at preventing symptomatic Covid-19. Effectiveness of two doses of CoronaVac was 41% (95% CI 27.1- 52.2) against symptomatic Covid-19, 85% (95% CI 59.5-94.8) against severe Covid-19 and (75%; 95% CI 27.9- 91.2) in preventing progression to severe Covid-19 among those infected. Conclusion: A complete regimen of CoronaVac in pregnant women was effective in preventing symptomatic Covid-19, and highly effective against severe illness in a setting that combines high disease burden and elevated Covid-19 related maternal deaths.Funding Information: This study is part of the VigiVac Fiocruz program, partially supported by a donation from the "Fazer o bem faz bem" program. EPS is funded by the Wellcome Trust [Grant number 213589/Z/18/Z]. Declaration of Interests: We declare no competing interests. VO, VB, MB, and MB-N are employees from Fiocruz, a federal public institution, which manufactures Vaxzevria in Brazil, through a full technology transfer agreement with AstraZenecaEthics Approval Statement: This study analysed de-identified data and was approved by the National Ethics committee (CONEP) (CAAE registration no. 50199321.9.0000.0040).

The effectiveness of Vaxzevria and CoronaVac vaccines: A nationwide longitudinal retrospective study of 61 million Brazilians (VigiVac-COVID19). (preprint)

BackgroundHigh rates of virus transmission and the presence of variants of concern can affect vaccine effectiveness (VE). Both conditions occur in low-income countries, which primarily use viral vector or inactivated virus vaccine technologies. Such countries conducted few VE analyses, and most lack the power to evaluate effectiveness in subgroups. MethodsThe present retrospective cohort study evaluated the effectiveness of Vaxzevria and CoronaVac vaccines for COVID-19-related infection in 75,919,840 Brazilian vaccinees from January 18 to July 24, 2021. Study outcomes included documented infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19-related hospitalization, ICU admission, and death. We estimated VE using Cox regression adjusted for individual demographic characteristics. ResultsVaccination with Vaxzevria or CoronaVac was effective against SARS-CoV-2 infection and highly effective against hospitalization, ICU admission, and death in individuals up to 79 years. From 80-89 years of age, Vaxzevria led to 89.9%(95CI:87.7-91.7) VE against death versus 67.2%(95CI:63.6-70.5) for CoronaVac. Above 90 years, 65.4%(95CI:46.1-77.8) protection was conferred to Vaxzevria-vaccinated individuals versus 33.6%(95CI:21.9-43.5) in CoronaVac-vaccinated individuals. Furthermore, the post-vaccination daily incidence rate shows a stepwise increase from younger to elder decades of life. ConclusionsVaxzevria demonstrated overall effectiveness against severe COVID-19 up to 89 years and CoronaVac up to 79 years of age. There is a stepwise effectiveness reduction for both vaccines for each decade of life. Our results suggest that individuals aged 80 years or older may benefit from an expedited booster dose. Ongoing evaluations, including any additional vaccines authorized, are crucial to monitoring long-term vaccine effectiveness.

Post-Acute COVID Syndrome, the Aftermath of Mild to Severe COVID-19 in Brazilian Patients (preprint)

ABSTRACT Objective To describe persistent symptoms after acute COVID-19 in different spectrum of disease severity in a population from an upper/middle income country, and identify the main clinical features impacting the quality of life. Design Cross-sectional study. Setting Outpatient clinic from a public post-COVID-19 health center (CPC) at Bahia-Brazil, a state where 80% are black or mixed race. Participants Patients admitted between August 2020 and February 2021 with symptoms at least one month after the onset of COVID-19. Main outcome measures PACS and related disorders such as hospitalization one month or later after disease onset, biochemical dysregulation and reduced quality of life (EQ-5D-5L questionnaire). Results Among 683 individuals assisted at CPC in this period, 602 were recruited. Patients had average of 52 (±14.6) years, 355 (59%) were female, 528 (88%) black/brown. Individuals were classified as mild (39.9%), moderate (27.9%) or severe (32.2%) during acute illness if outpatient, hospitalized non-UCI or UCI, respectively. Most patients reported a polysymptomatic profile, in median eight (IQR=6-9) acute symptoms. The most frequent residual symptoms were dyspnea (66%), fatigue (62%) and chest pain (43%). Women were more affected regardless disease severity at acute stage: presented more residual symptoms [4 (2-6) vs 3 (2-4)] and a higher impact in quality of life. Altered HbA1c [(184/275 (66.9%)], high CRP levels [195/484 (40.3%)] and anemia [143/545 (26.2%)] were the most common abnormalities in laboratory exams. 76 patients presented HbA1c above 6.4% although only 42 referred previous diagnosis of diabetes mellitus. After one month of disease onset, 30 patients required hospitalization, including seven cases with mild acute illness. Hospital admission after acute disease was required on 30 patients, seven (23%) were mild. Quality of life had been affected for 357/404 (88.4%) patients according to EuroQoL (EQ-5D-5L), mainly the domains of anxiety/depression [severe or extreme anxiety for 79/401 (19.7%)] and pain/discomfort [severe or extreme pain for 71/403 (17.6%)]. The median EuroQoL Global Score was 70 [IQR 50-80]. PACS symptoms such as dyspnea, chest pain, and fatigue, was associated with decreased quality of life. Conclusions PACS, such as dyspnea, chest pain and fatigue, occurred after variable degree of disease severity. Among this majority black/mixed-race patients, woman seemed to be more affected. Other consequences included post-acute hospitalization, and abnormal glucose metabolism and reduced quality of life. Summary Box Section 1: What is already known on this topic: ✓ Post-Acute COVID Syndrome (PACS) comprises a set of persistent or new-onset symptoms after illness onset. ✓ As far as we know, there are no studies describing PACS in a population principally black and mixed-race. Additionally, few studies have addressed PACS among outpatients. Section 2: What this study adds: ✓ Similar PACS were reported after mild, moderate and severe illness. Dyspnea, fatigue and chest pain were the most prevalent symptoms in this population presenting majority of black/mixed-race patients. ✓ Women presented more residual symptoms, a higher frequency of myalgia and worse score for mobility, usual activities, anxiety/depression, and pain. ✓ Hospitalization may occur one month or later after mild or moderate/severe acute infection due to respiratory and vascular disorders. Abnormal glucose metabolism was detected in the absence of previous diagnosis of diabetes mellitus.