RESUMO
Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and, if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers. We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza, and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV). We demonstrate that circulating markers of complement activation (i.e., sC5b-9) are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., Ang2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials.
RESUMO
BACKGROUND: In Tamil Nadu, India, bacille Calmette-Guérin, diphtheria-tetanus-pertussis, oral poliomyelitis, hepatitis B, and measles vaccines are part of the routine immunization schedule and are available free from government health centers. All other vaccines are optional and available in the private sector at a cost to families. This study assesses immunization rates of routine and optional vaccines and examines parental attitudes toward vaccines in Pallavapuram, Tamil Nadu. METHODS: The cluster sampling method was used to estimate immunization coverage. Seven children 18 to 36 months old were selected from 30 clusters for a total sample of 210 children. Demographics and vaccination data were collected from interviews and immunization records. Predictors of vaccination status were identified with logistic regression models. In addition, 21 parents participated in semi-structured interviews regarding their attitudes toward vaccination. Interviews were analyzed qualitatively for themes. RESULTS: Eighty one percent of children were fully immunized with routine vaccines. However, only 21% received all "major" optional vaccines, defined as 3 doses of Haemophilus influenzae type b vaccine, one dose of measles, mumps, rubella vaccine, and one dose of varicella zoster virus vaccine. Birth in a private hospital (OR 5.6, 95% CI 1.3 to 22.9, P<0.01), higher income (P=0.03), and maternal completion of high school (OR 6.4, 95% CI 1.5 to 27.6, P<0.01) were significant predictors of receiving all major optional vaccines. Elucidated themes from interviews included (1) strong parental support for immunizations, (2) low concern for side effects, and (3) low uptake of optional vaccines due to high cost and lack of awareness. CONCLUSIONS: Coverage of optional vaccines is low despite positive attitudes toward immunizations. Efforts to reduce cost and increase awareness of these vaccines particularly among low-income families or to include these vaccines in the routine schedule may increase uptake and reduce morbidity and mortality from vaccine-preventable diseases.