Chemokines, soluble PD-L1, and immune cell hyporesponsiveness are distinct features of SARS-CoV-2 critical illness.

Critically ill patients manifest many of the same immune features seen in coronavirus disease 2019 (COVID-19), including both "cytokine storm" and "immune suppression." However, direct comparisons of molecular and cellular profiles between contemporaneously enrolled critically ill patients with and without severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited. We sought to identify immune signatures specifically enriched in critically ill patients with COVID-19 compared with patients without COVID-19. We enrolled a multisite prospective cohort of patients admitted under suspicion for COVID-19, who were then determined to be SARS-CoV-2-positive (n = 204) or -negative (n = 122). SARS-CoV-2-positive patients had higher plasma levels of CXCL10, sPD-L1, IFN-γ, CCL26, C-reactive protein (CRP), and TNF-α relative to SARS-CoV-2-negative patients adjusting for demographics and severity of illness (Bonferroni P value < 0.05). In contrast, the levels of IL-6, IL-8, IL-10, and IL-17A were not significantly different between the two groups. In SARS-CoV-2-positive patients, higher plasma levels of sPD-L1 and TNF-α were associated with fewer ventilator-free days (VFDs) and higher mortality rates (Bonferroni P value < 0.05). Lymphocyte chemoattractants such as CCL17 were associated with more severe respiratory failure in SARS-CoV-2-positive patients, but less severe respiratory failure in SARS-CoV-2-negative patients (P value for interaction < 0.01). Circulating T cells and monocytes from SARS-CoV-2-positive subjects were hyporesponsive to in vitro stimulation compared with SARS-CoV-2-negative subjects. Critically ill SARS-CoV-2-positive patients exhibit an immune signature of high interferon-induced lymphocyte chemoattractants (e.g., CXCL10 and CCL17) and immune cell hyporesponsiveness when directly compared with SARS-CoV-2-negative patients. This suggests a specific role for T-cell migration coupled with an immune-checkpoint regulatory response in COVID-19-related critical illness.

Self-reported reactogenicity of CoronaVac (Sinovac) compared with Comirnaty (Pfizer-BioNTech): A prospective cohort study with intensive monitoring.

OBJECTIVE: CoronaVac (Sinovac) Covid-19 vaccine has recently been approved for emergency use by the World Health Organization. However, data on its reactogenicity in real-world settings is scant. This study aimed to compare self-reported post-vaccination adverse reactions between CoronaVac and Comirnaty (Pfizer-BioNTech). METHODS: We adopted a prospective cohort study design using online surveys from the day of first-dose vaccination with intensive follow-up through two weeks after the second dose (11 time points). The primary outcome was adverse reactions (any versus none) and secondary outcomes were the sub-categories of adverse reactions (local, systemic, and severe allergic reactions). Potential effect modification across multimorbidity status, older age, and sex was examined. RESULTS: In total, 2,098 participants who were scheduled to complete the 14th-day survey were included, with 46.2% receiving Comirnaty. Retention rate two weeks after the second dose was 81.0% for the CoronaVac group and 83.6% for the Comirnaty group. Throughout the follow-up period, 801 (82.7%) of those receiving Comirnaty and 543 (48.1%) of those receiving CoronaVac reported adverse reactions. Adjusted analysis suggested that compared with Comirnaty, CoronaVac was associated with 83%-reduced odds of any adverse reactions [adjusted odds ratio (AOR) = 0.17, 95% confidence interval (CI) 0.15-0.20], 92%-reduced odds of local adverse reactions (AOR = 0.08, 95% CI 0.06-0.09), and 76%-reduced odds of systemic adverse reactions (AOR = 0.24, 95% CI 0.16-0.28). No significant effect modification was identified. CONCLUSION: This post-marketing study comparing the reactogenicity of Covid-19 vaccines suggests a lower risk of self-reported adverse reactions following vaccination with CoronaVac compared with Comirnaty.

Multimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong.

Prior research using electronic health records for Covid-19 vaccine safety monitoring typically focuses on specific disease groups and excludes individuals with multimorbidity, defined as ≥2 chronic conditions. We examine the potential additional risk of adverse events 28 days after the first dose of CoronaVac or Comirnaty imposed by multimorbidity. Using a territory-wide public healthcare database with population-based vaccination records in Hong Kong, we analyze a retrospective cohort of patients with chronic conditions. Thirty adverse events of special interest according to the World Health Organization are examined. In total, 883,416 patients are included and 2,807 (0.3%) develop adverse events. Results suggest vaccinated patients have lower risks of adverse events than unvaccinated individuals, multimorbidity is associated with increased risks regardless of vaccination, and the association of vaccination with adverse events is not modified by multimorbidity. To conclude, we find no evidence that multimorbidity imposes extra risks of adverse events following Covid-19 vaccination.

Comparing self-reported reactogenicity between adolescents and adults following the use of BNT162b2 (Pfizer-BioNTech) messenger RNA COVID-19 vaccine: a prospective cohort study.

OBJECTIVES: Although clinical data have shown that the BNT162b2 vaccine, which is widely used in many countries, is safe and effective as a protection against the SARS-CoV-2 infection, extant research in adverse reactions using real-world data of various sociodemographic characteristics is scant. METHODS: We conducted a prospective cohort study to compare age differences in self-reported reactogenicity of BNT162b2 in Hong Kong. A total of 1,516 participants were intensively followed up for two weeks following both doses of BNT162b2 vaccination, during which their basic demographic, health conditions, and medication information were collected. RESULTS: Results from the generalized mixed model showed that compared with adults aged 18 to 59 years, older adults aged 60 years or above had a lower risk of adverse reactions and adolescents aged 12 to 17 years had a moderately higher risk. CONCLUSIONS: Results of this study should be informative to parents considering BNT162b2 vaccination for their children in that moderately increased reactogenicity compared with adults is anticipated.

Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study.

BACKGROUND: Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. METHODS: We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. RESULTS: In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. CONCLUSIONS: These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.