Regular Use of Ivermectin as Prophylaxis for COVID-19 Led Up to a 92% Reduction in COVID-19 Mortality Rate in a Dose-Response Manner: Results of a Prospective Observational Study of a Strictly Controlled Population of 88,012 Subjects.

Background We have previously demonstrated that ivermectin used as prophylaxis for coronavirus disease 2019 (COVID-19), irrespective of the regularity, in a strictly controlled citywide program in Southern Brazil (Itajaí, Brazil), was associated with reductions in COVID-19 infection, hospitalization, and mortality rates. In this study, our objective was to determine if the regular use of ivermectin impacted the level of protection from COVID-19 and related outcomes, reinforcing the efficacy of ivermectin through the demonstration of a dose-response effect. Methods This exploratory analysis of a prospective observational study involved a program that used ivermectin at a dose of 0.2 mg/kg/day for two consecutive days, every 15 days, for 150 days. Regularity definitions were as follows: regular users had 180 mg or more of ivermectin and irregular users had up to 60 mg, in total, throughout the program. Comparisons were made between non-users (subjects who did not use ivermectin), and regular and irregular users after multivariate adjustments. The full city database was used to calculate and compare COVID-19 infection and the risk of dying from COVID-19. The COVID-19 database was used and propensity score matching (PSM) was employed for hospitalization and mortality rates. Results Among 223,128 subjects from the city of Itajaí, 159,560 were 18 years old or up and were not infected by COVID-19 until July 7, 2020, from which 45,716 (28.7%) did not use and 113,844 (71.3%) used ivermectin. Among ivermectin users, 33,971 (29.8%) used irregularly (up to 60 mg) and 8,325 (7.3%) used regularly (more than 180 mg). The remaining 71,548 participants were not included in the analysis. COVID-19 infection rate was 49% lower for regular users (3.40%) than non-users (6.64%) (risk rate (RR): 0.51; 95% CI: 0.45-0.58; p < 0.0001), and 25% lower than irregular users (4.54%) (RR: 0.75; 95% CI: 0.66-0.85; p < 0.0001). The infection rate was 32% lower for irregular users than non-users (RR: 0.68; 95% CI: 0.64-0.73; p < 0.0001). Among COVID-19 participants, regularusers were older and had a higher prevalence of type 2 diabetes and hypertension than irregular and non-users. After PSM, the matched analysis contained 283 subjects in each group of non-users and regular users, between regular users and irregular users, and 1,542 subjects between non-users and irregular users. The hospitalization rate was reduced by 100% in regular users compared to both irregular users and non-users (p < 0.0001), and by 29% among irregular users compared to non-users (RR: 0.781; 95% CI: 0.49-1.05; p = 0.099). Mortality rate was 92% lower in regular users than non-users (RR: 0.08; 95% CI: 0.02-0.35; p = 0.0008) and 84% lower than irregular users (RR: 0.16; 95% CI: 0.04-0.71; p = 0.016), while irregular users had a 37% lower mortality rate reduction than non-users (RR: 0.67; 95% CI: 0.40-0.99; p = 0.049). Risk of dying from COVID-19 was 86% lower among regular users than non-users (RR: 0.14; 95% CI: 0.03-0.57; p = 0.006), and 72% lower than irregular users (RR: 0.28; 95% CI: 0.07-1.18; p = 0.083), while irregular users had a 51% reduction compared to non-users (RR: 0.49; 95% CI: 0.32-0.76; p = 0.001). Conclusion Non-use of ivermectin was associated with a 12.5-fold increase in mortality rate and a seven-fold increased risk of dying from COVID-19 compared to the regular use of ivermectin. This dose-response efficacy reinforces the prophylactic effects of ivermectin against COVID-19.

The Importance of Radiological Patterns and Small Airway Disease in Long-Term Follow-Up of Postacute COVID-19: A Preliminary Study.

Postacute COVID-19 has become a relevant public health problem, and radiological and pulmonary function tests are tools that help physicians in decision-making. The objectives of this study are to characterize the findings and patterns on a chest radiograph (CXR) and computed tomography (CT) that are most important in the postacute phase and to evaluate how these changes correlate with clinical data, spirometry, and impulse oscillometry (IOS). This was a retrospective study of 29 patients who underwent CXR, CT, spirometry, and IOS. The inclusion criteria were age >18 years and persistent respiratory symptoms after four weeks. The exclusion criteria were radiological exams with low technical quality and non-COVID-19 acute lung diseases. The inferential analysis was carried out with the chi-square (χ 2) or Fisher's exact test to evaluate the interrelationships between the clinical and COVID-19 variables according to spirometry, IOS, CT, and CXR. In our sample, 19 patients were women (65.5%). The predominance of abnormal spirometry was associated with CT's moderate/severe degree of involvement (p = 0.017; 69.2%, CI 95%: 44.1%-94.3%). There was no significant association between IOS and tomographic and radiographic parameters. A significant association was found between the classifications of the moderate/severe and normal/mild patterns on CT and CXRs (p = 0.003; 93.3%, CI 95%: 77.8%-100%). Patients with moderate/severe impairment on CXR were associated with a higher frequency of hospitalization (p = 0.033; 77.8%, CI 95%: 58.6%-97.0%) and had significantly more moderate/severe classifications in the acute phase than the subgroup with normal/mild impairment on CXR (p = 0.017; 88.9%, CI 95%: 74.4%-100%). In conclusion, the results of this study show that CXR is a relevant examination and may be used to detect nonspecific alterations during the follow-up of post-COVID-19 patients. Small airway disease is an important finding in postacute COVID-19 syndrome, and we postulate a connection between this pattern and the persistently low-level inflammatory state of the lung.

Correction: Ivermectin Prophylaxis Used for COVID-19: A Citywide, Prospective, Observational Study of 223,128 Subjects Using Propensity Score Matching.

[This corrects the article DOI: 10.7759/cureus.21272.].

Ivermectin Prophylaxis Used for COVID-19: A Citywide, Prospective, Observational Study of 223,128 Subjects Using Propensity Score Matching.

BACKGROUND: Ivermectin has demonstrated different mechanisms of action that potentially protect from both coronavirus disease 2019 (COVID-19) infection and COVID-19-related comorbidities. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of ivermectin, a citywide prevention program using ivermectin for COVID-19 was implemented in Itajaí, a southern city in Brazil in the state of Santa Catarina. The objective of this study was to evaluate the impact of regular ivermectin use on subsequent COVID-19 infection and mortality rates. MATERIALS AND METHODS: We analyzed data from a prospective, observational study of the citywide COVID-19 prevention with ivermectin program, which was conducted between July 2020 and December 2020 in Itajaí, Brazil. Study design, institutional review board approval, and analysis of registry data occurred after completion of the program. The program consisted of inviting the entire population of Itajaí to a medical visit to enroll in the program and to compile baseline, personal, demographic, and medical information. In the absence of contraindications, ivermectin was offered as an optional treatment to be taken for two consecutive days every 15 days at a dose of 0.2 mg/kg/day. In cases where a participating citizen of Itajaí became ill with COVID-19, they were recommended not to use ivermectin or any other medication in early outpatient treatment. Clinical outcomes of infection, hospitalization, and death were automatically reported and entered into the registry in real time. Study analysis consisted of comparing ivermectin users with non-users using cohorts of infected patients propensity score-matched by age, sex, and comorbidities. COVID-19 infection and mortality rates were analyzed with and without the use of propensity score matching (PSM). RESULTS: Of the 223,128 citizens of Itajaí considered for the study, a total of 159,561 subjects were included in the analysis: 113,845 (71.3%) regular ivermectin users and 45,716 (23.3%) non-users. Of these, 4,311 ivermectin users were infected, among which 4,197 were from the city of Itajaí (3.7% infection rate), and 3,034 non-users (from Itajaí) were infected (6.6% infection rate), with a 44% reduction in COVID-19 infection rate (risk ratio [RR], 0.56; 95% confidence interval (95% CI), 0.53-0.58; p < 0.0001). Using PSM, two cohorts of 3,034 subjects suffering from COVID-19 infection were compared. The regular use of ivermectin led to a 68% reduction in COVID-19 mortality (25 [0.8%] versus 79 [2.6%] among ivermectin non-users; RR, 0.32; 95% CI, 0.20-0.49; p < 0.0001). When adjusted for residual variables, reduction in mortality rate was 70% (RR, 0.30; 95% CI, 0.19-0.46; p < 0.0001). There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001). After adjustment for residual variables, reduction in hospitalization rate was 67% (RR, 0.33; 95% CI, 023-0.66; p < 0.0001). CONCLUSION: In this large PSM study, regular use of ivermectin as a prophylactic agent was associated with significantly reduced COVID-19 infection, hospitalization, and mortality rates.

Chest computed tomography in COVID-19 pneumonia: a retrospective study of 155 patients at a university hospital in Rio de Janeiro, Brazil.

OBJECTIVE: To define diagnostic criteria for coronavirus disease 2019 (COVID-19) on computed tomography (CT); to study the correlation between CT and polymerase chain reaction (PCR) testing for infection with severe acute respiratory syndrome coronavirus 2; and to determine whether the extent of parenchymal involvement and the need for mechanical ventilation are associated with the CT findings and clinical characteristics of patients with COVID-19. MATERIALS AND METHODS: This was a retrospective study of 155 patients with COVID-19 treated between March and May 2020. We attempted to determine whether the CT findings correlated with age and clinical variables, as well as whether the need for mechanical ventilation correlated with the extent of the pulmonary involvement. RESULTS: On average, the patients with COVID-19 were older than were those without (mean age, 54.8 years vs. 45.5 years; p = 0.031). The most common CT finding (seen in 88.6%) was ground-glass opacity, which correlated significantly with a diagnosis of COVID-19 (p = 0.0001). The CT findings that correlated most strongly with the need for mechanical ventilation were parenchymal bands (p = 0.013), bronchial ectasia (p = 0.046), and peribronchovascular consolidations (p = 0.012). The presence of one or more comorbidities correlated significantly with more extensive parenchymal involvement (p = 0.023). For the diagnosis of COVID-19, CT had a sensitivity of 84.3%, a specificity of 36.7%, and an accuracy of 73.5% (p = 0.012 vs. PCR). CONCLUSION: The patterns of CT findings are useful for the diagnosis of COVID-19 and the evaluation of disease severity criteria. The presence of any comorbidity is associated with greater severity of COVID-19.

OBJETIVO: Definir os critérios diagnósticos da COVID-19 na tomografia computadorizada (TC), estudar a concordância entre a TC e o PCR e determinar a associação da extensão do envolvimento parenquimatoso e ventilação mecânica com os achados tomográficos e características clínicas da amostra. MATERIAIS E MÉTODOS: Estudo de 155 pacientes com COVID-19 atendidos entre março e maio de 2020. Tentamos determinar se os achados da TC se correlacionavam com a idade e variáveis clínicas, bem como se a necessidade de ventilação mecânica se correlacionava com a extensão do envolvimento pulmonar. RESULTADOS: A faixa etária dos pacientes com COVID-19 (54,8 anos) foi maior do que a dos pacientes sem a doença (45,5 anos) (p = 0,031). Opacidades em vidro fosco foram as alterações mais frequentes (88,6%; p = 0,0001). Bandas parenquimatosas (p = 0,013), ectasia brônquica (p = 0,046) e consolidações peribroncovasculares (p = 0,012) foram mais frequentes nos pacientes que necessitaram de ventilação mecânica. Pacientes com comorbidades apresentaram envolvimento parenquimatoso mais extenso (p = 0,023). A TC apresentou sensibilidade de 84,3%, especificidade de 36,7% e acurácia de 73,5% (p = 0,012). CONCLUSÃO: Os padrões de TC são úteis para o diagnóstico de COVID-19 e avaliação dos critérios de gravidade da doença. Pacientes com comorbidades estão associados a condições clínicas mais graves.