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PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333832


BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses >=14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%;95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were >=50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%;95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%;95% CI: 85.5 to 94.7%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277339


Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a rapid increase in the incidence of acute respiratory distress syndrome (ARDS). The distinct features of pulmonary biology in COVID-19 ARDS compared to other causes of ARDS, including other lower respiratory tract infections (LRTIs), are not well understood. Methods: Tracheal aspirates (TA) and plasma were collected within five days of intubation from mechanically ventilated adults admitted to one of two academic medical centers. ARDS and LRTI diagnoses and were verified by study physicians. Subjects were excluded if they received immunosuppression. TA from subjects with COVID-ARDS was compared to gene expression in TA from subjects with other causes of ARDS (OtherARDS) or mechanically ventilated control subjects without evidence of pulmonary pathology (NoARDS). Plasma concentrations of IL-6, IL-8, and protein C also were compared between these groups. Upstream regulator and pathway analysis was performed on significantly differentially expressed genes with Ingenuity Pathway Analysis (IPA). Subgroup analyses were performed to compare gene expression in COVID to ARDS associated with other viral LRTIs and bacterial LRTIs. The association of interferon-stimulated gene expression with SARS-CoV2 viral load was compared to the same association in nasopharyngeal swabs in a cohort of subjects with mild SARS-CoV2. Results: TA sequencing was available from 15 subjects with COVID, 32 subjects with other causes of ARDS (OtherARDS), and 5 mechanically ventilated subjects without evidence of pulmonary pathology (NoARDS). 696 genes were differentially expressed between COVID and OtherARDS (Figure 1A). IL-6, IL-8, B-cell receptor, and hypoxia inducible factor-1a signaling were attenuated in COVID compared to OtherARDS. Peroxisome proliferator-activated receptor (PPAR) and PTEN signaling were higher in COVID compared to OtherARDS (Figure 1B). Plasma levels of IL-6, IL-8, and protein C were not significantly different between COVID and OtherARDS. In subgroup analyses, IL-8 signaling was higher in COVID compared to viral LRTI, but lower than bacterial LRTI. Type I/III interferon was higher in COVID compared to bacterial ARDS, but lower compared to viral ARDS (Figure 1C). Compared to nasopharyngeal swabs from subjects with mild COVID-19, expression of several interferon stimulated genes was less strongly correlated with SARS-CoV2 viral load in TA (Figure 1D). IPA identified several candidate medications to treat COVID-19, including dexamethasone, G-CSF, and etanercept. Conclusions: TA sequencing identifies unique features of the host response in COVID-19. These differentially expressed pathways may represent potential therapeutic targets. An impaired interferon response in the lung may increase susceptibility to severe SARS-COV2.

American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277310


Introduction: There has been substantial lay press interest in whether patients who die of COVID-19 are dying of COVID-19 or other underlying illnesses. We have previously described a clinician scoring system that delineates whether a patient's prognosis is driven by acute illness vs comorbidities. In this study we compared this clinician phenotyping system in patients with COVID-19 to ICU biobank patients enrolled prior to 2020. Methods: Clinician phenotyping was performed on patients enrolled into 2 Stanford ICU biobanks: (1) Patients admitted to Stanford ICU before 2020 with at least one ARDS risk factor (non-COVID-19 cohort) and (2) Patients admitted to the ICU with confirmed COVID-19 infection (COVID-19 cohort). The roles of each of the following categories in determining prognosis at time of enrollment were scored from 1-5 (1 being non-contributory and 5 being highly contributory): goals of care, comorbidities, baseline functional status, acute multi-system organ failure (MSOF), ARDS, acute neurologic injury, and terminal illness. Each patient's primary determinant of mortality was then grouped into one of four categories: (1) MSOF or ARDS (>=4 for ARDS or multi-organ failure), (2) Comorbidities (>=4 for goals of care, comorbidities, acute neurologic injury, or baseline functional status), (3) Mixed (>= 4 for both of the above), or (4) None (<4 for all categories). The odds ratio for prognostic subgroupings was compared between patient cohorts.Results: Clinician phenotyping was performed on 70 non-COVID-19 patients admitted to the ICU with at least one risk factor for ARDS, and 28 patients with COVID-19 admitted to the ICU. Compared to the general ICU population, COVID-19 patients were younger (median age 53 vs 71), more likely to be male (71% vs 54%), and more likely to identify as Hispanic (64% vs 13%). 60-day mortality was higher in the COVID-19 group (29% vs 20%). ARDS or MSOF was the primary determinant of prognosis in 64% of patients with COVID-19 compared to 31% of traditional ICU patients (OR 3.9, 95% CI 1.6-9.9, Figure 1). Only 11% of COVID-19 patients' primary determinant of prognosis was comorbidities or goals of care relative to 31% in the traditional ICU population (OR 0.26, 95% CI 0.07-0.9).Conclusion: In this study, ARDS or MSOF is far more likely to be the main risk factor for death in patients with COVID-19 than in a traditional ICU population. This suggests that most COVID-19 fatalities are attributable to acute infection with SARS-CoV-2 rather than progression of underlying disease.