Humoral and Cellular Response and Associated Variables Nine Months following BNT162b2 Vaccination in Healthcare Workers.

In this study, we aimed to illustrate the trajectory of humoral and cellular immunity nine months after primary vaccination with the BNT162b2 mRNA vaccine among 189 healthcare workers (HCWs). Additionally, we endeavored to identify correlations between immunity parameters and a number of common variables and comorbidities. A total of 189 healthcare workers (HCWs), vaccinated against COVID-19, were finally included in the study. All of the subjects had received two doses of the BNT162b2 vaccine; had undergone antibody tests one, four and nine months post-vaccination; and had completed a medical questionnaire. Further samples taken at nine months were tested for cellular immunity. No participants had evidence of COVID-19 infection pre- or post-vaccination. An anti-S1 receptor binding domain (RBD) antibody assay was used to assess humoral response, and cellular immunity was estimated with an INF-γ release assay (IGRA). Statistical analysis was performed using STATA. We report a statistically significant antibody drop over time. Being above the age of 40 or a smoker reduces the rise of antibodies by 37% and 28%, respectively. More than half of the participants did not demonstrate T-cell activation at nine months. Female gender and antibody levels at four months predispose detection of cellular immunity at nine months post-immunization. This study furthers the qualitative, quantitative, and temporal understanding of the immune response to the BNT162b2 mRNA vaccine and the effect of correlated factors.

COVID-19 Therapeutics: Improvise-Adapt-Learn.

"In the midst of chaos, there is also opportunity"-Sun Tzu, The Art of War [...].

Diabetic Ketoacidosis Was Associated with High Morbidity and Mortality in Hospitalized Patients with COVID-19 in the NYC Public Health System

Background: COVID-19 has been associated with a higher risk of death in patients with diabetes mellitus (DM). However, there is a dearth of data regarding the effects of diabetic ketoacidosis (DKA) in these patients. We explored the in-hospital outcomes of patients who presented with COVID-19 and DKA. Methods: A propensity score-matched observational retrospective cohort study was conducted in hospitalized patients with COVID-19 in the public healthcare system of New York City from 1 March 2020 to 31 October 2020. Patients were matched, and a subgroup analysis of patients with DKA and COVID-19 and patients without COVID-19 was conducted. Results: 13,333 (16.0%) patients with COVID-19 and 70,005 (84.0%) without COVID-19 were included in the analysis. The in-hospital mortality rate was seven-fold in patients with DKA and COVID-19 compared to patients with COVID-19 and without DKA (80 (36.5%) vs. 11 (5.4%), p < 0.001). Patients with COVID-19 and DKA had a two-fold higher likelihood for in-hospital death (OR: 1.95;95% CI: 1.41–2.70;p < 0.001) after adjusting for multiple variables. Conclusions: DKA was associated with significantly higher in-hospital mortality in hospitalized patients with COVID-19.

Incidence of Stroke in Randomized Trials of COVID-19 Therapeutics: A Systematic Review and Meta-Analysis.

BACKGROUND: COVID-19 has been frequently associated with an increased risk of thrombotic complications. There have also been reports of an increased likelihood of stroke, although its true incidence in patients with COVID-19 is currently unknown. METHODS: Electronic databases PubMed and Scopus were searched from inception up to July 30, 2021 to identify randomized controlled studies in patients with confirmed COVID-19 undergoing one or more interventions. Studies were screened for eligibility using a predefined inclusion criterion and selected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model meta-analysis was conducted, and heterogeneity was assessed using I-squared test. RESULTS: Out of 3960 potentially eligible articles, 77 randomized studies (38 732 patients) were included. Mean age of the study population was 55±9.3 years. Females constituted 38% of the study population and mean duration of follow-up after study enrollment was 23±12.9 days. Cumulative incidence of stroke in the overall study population was 0.001 (95% CI, 0.001-0.002) with a total of 65 events in 38 732 patients, corresponding to an absolute incidence of 0.168%. Incidence of stroke in the inpatient population was 0.001 (95% CI, 0.001-0.002; 65 events in 37 069 patients), corresponding to an absolute incidence of 0.175%. No strokes were observed in the outpatient setting. CONCLUSIONS: The overall incidence of stroke in patients with COVID-19 appears to be lower than that reported in previous observational reports.

Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans.

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.

Remdesivir in the Treatment of COVID-19: A Propensity Score-Matched Analysis from a Public Hospital in New York City Assessing Renal and Hepatic Safety.

While the relative efficacy of remdesivir as a therapeutic agent in selected patients with COVID-19 has been established, safety concerns have been raised regarding potential nephrotoxicity and hepatotoxicity. Our main objective was to investigate the kidney- and liver-related safety outcomes in patients with COVID-19 treated with remdesivir in a public hospital in New York. A propensity score-matched retrospective study was conducted in hospitalized patients with COVID-19 from 1 June 2020 to 10 March 2021. A total of 927 patients were included in this study (remdesivir: 427, non-remdesivir: 500; women: 51.8%; median age 61 years; median BMI: 28.5 kg/m2). Matching without replacement yielded a cohort of 248 patients (124 in each group). In the matched cohort, the remdesivir group had a significantly lower rate of acute kidney injury (AKI) (12.1% vs. 21.8%, p = 0.042), a lower rate of acute liver injury (ALI) on the verge of statistical significance (7.3% vs. 14.5%, p = 0.067), and non-significantly lower death rate (13.7% vs. 16.1%, p = 0.593) compared to the non-remdesivir group. Multivariable analyses revealed that patients treated with remdesivir were found to be associated with a significantly lower likelihood for AKI (OR: 0.40; 95% CI: 0.24-0.67, p < 0.001), no association was found for ALI (OR: 0.68; 95% CI: 0.35-1.30, p = 0.241), while a trend towards an association of patients treated with remdesivir with a lower likelihood for in-hospital death was observed (OR: 0.57; 95% CI: 0.32-1.01, p = 0.053). In conclusion, no safety concerns with regards to renal and liver outcomes were raised in patients with COVID-19 treated with remdesivir. Instead, there were signals of possible nephroprotection and improved in-hospital mortality.

Statin Use in Hospitalized Patients with COVID-19: A Comprehensive Analysis of the New York City Public Hospital System.

INTRODUCTION: Statins have been commonly used for primary and secondary cardiovascular prevention. We hypothesized that statins may improve in-hospital outcomes for hospitalized patients with Coronavirus disease 2019 (COVID-19) due to its known anti-inflammatory effects. METHODS: We conducted a retrospective study at the largest municipal health care system in the United States, including adult patients who were hospitalized for COVID-19 between March 1 and December 1, 2020. The primary endpoint was in-hospital death. Propensity score matching was conducted to balance possible confounding variables between patients receiving statins during hospitalization (statin group) and those not receiving statins (non-statin group). Multivariate logistic regression was used to evaluate the association of statin use and other variables with in-hospital outcomes. RESULTS: There were 8897 patients eligible for study enrollment, with 3359 patients in the statin group and 5538 patients in the non-statin group. After propensity score matching, both the statin and non-statin groups included 2817 patients. Multivariate logistic regression analysis showed that the statin group had a significantly lower risk of in-hospital mortality (odds ratio 0.71; 95% confidence interval, 0.63-0.80; P < .001) and mechanical ventilation (OR 0.80; 95% confidence interval, 0.71-0.90; P < .001) compared with the non-statin group. CONCLUSION: Statin use was associated with lower likelihood of in-hospital mortality and invasive mechanical ventilation in hospitalized patients with COVID-19.

Obesity, Inflammation, and Mortality in COVID-19: An Observational Study from the Public Health Care System of New York City.

Severe obesity increases the risk for negative outcomes in patients with coronavirus disease 2019 (COVID-19). Our objectives were to investigate the effect of BMI on in-hospital outcomes in our New York City Health and Hospitals' ethnically diverse population, further explore this effect by age, sex, race/ethnicity, and timing of admission, and, given the relationship between COVID-19 and hyperinflammation, assess the concentrations of markers of systemic inflammation in different BMI groups. A retrospective study was conducted in hospitalized patients with COVID-19 in the public health care system of New York City from 1 March 2020 to 31 October 2020. A total of 8833 patients were included in this analysis (women: 3593, median age: 62 years). The median body mass index (BMI) was 27.9 kg/m2. Both overweight and obesity were independently associated with in-hospital death. The association of overweight and obesity with death appeared to be stronger in men, younger patients, and individuals of Hispanic ethnicity. We did not observe higher concentrations of inflammatory markers in patients with obesity as compared to those without obesity. In conclusion, overweight and obesity were independently associated with in-hospital death. Obesity was not associated with higher concentrations of inflammatory markers.

Assessment of the Association of COPD and Asthma with In-Hospital Mortality in Patients with COVID-19. A Systematic Review, Meta-Analysis, and Meta-Regression Analysis.

Together, chronic obstructive pulmonary disease (COPD) and asthma account for the most common non-infectious respiratory pathologies. Conflicting preliminary studies have shown varied effect for COPD and asthma as prognostic factors for mortality in coronavirus disease 2019 (COVID-19). The aim of this study was to explore the association of COPD and asthma with in-hospital mortality in patients with COVID-19 by systematically reviewing and synthesizing with a meta-analysis the available observational studies. MEDLINE, Scopus, and medRxiv databases were reviewed. A random-effects model meta-analysis was used, and I-square was utilized to assess for heterogeneity. In-hospital mortality was defined as the primary endpoint. Sensitivity and meta-regression analyses were performed. Thirty studies with 21,309 patients were included in this meta-analysis (1465 with COPD and 633 with asthma). Hospitalized COVID-19 patients with COPD had higher risk of death compared to those without COPD (OR: 2.29; 95% CI: 1.79-2.93; I2 59.6%). No significant difference in in-hospital mortality was seen in patients with and without asthma (OR: 0.87; 95% CI: 0.68-1.10; I2 0.0%). The likelihood of death was significantly higher in patients with COPD that were hospitalized with COVID-19 compared to patients without COPD. Further studies are needed to assess whether this association is independent or not. No significant difference was demonstrated in COVID-19-related mortality between patients with and without asthma.

Effect of Hydroxychloroquine on QTc in Patients Diagnosed with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Hydroxychloroquine or chloroquine with or without the concomitant use of azithromycin have been widely used to treat patients with SARS-CoV-2 infection, based on early in vitro studies, despite their potential to prolong the QTc interval of patients. OBJECTIVE: This is a systematic review and metanalysis designed to assess the effect of hydroxychloroquine with or without the addition of azithromycin on the QTc of hospitalized patients with COVID-19. MATERIALS AND METHODS: PubMed, Scopus, Cochrane and MedRxiv databases were reviewed. A random effect model meta-analysis was used, and I-square was used to assess the heterogeneity. The prespecified endpoints were ΔQTc, QTc prolongation > 500 ms and ΔQTc > 60 ms. RESULTS: A total of 18 studies and 7179 patients met the inclusion criteria and were included in this systematic review and meta-analysis. The use of hydroxychloroquine with or without the addition of azithromycin was associated with increased QTc when used as part of the management of patients with SARS-CoV-2 infection. The combination therapy with hydroxychloroquine plus azithromycin was also associated with statistically significant increases in QTc. Moreover, the use of hydroxychloroquine alone, azithromycin alone, or the combination of the two was associated with increased numbers of patients that developed QTc prolongation > 500 ms. CONCLUSION: This systematic review and metanalysis revealed that the use of hydroxychloroquine alone or in conjunction with azithromycin was linked to an increase in the QTc interval of hospitalized patients with SARS-CoV-2 infection that received these agents.

BMI and pneumonia outcomes in critically ill covid-19 patients: An international multicenter study.

OBJECTIVE: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19. METHODS: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively. RESULTS: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64]). CONCLUSIONS: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.

Sex-specific impact of severe obesity in the outcomes of hospitalized patients with COVID-19: a large retrospective study from the Bronx, New York.

It has been demonstrated that obesity is an independent risk factor for worse outcomes in patients with COVID-19. Our objectives were to investigate which classes of obesity are associated with higher in-hospital mortality and to assess the association between obesity and systemic inflammation. This was a retrospective study which included consecutive hospitalized patients with COVID-19 in a tertiary center. Three thousand five hundred thirty patients were included in this analysis (female sex: 1579, median age: 65 years). The median body mass index (BMI) was 28.8 kg/m2. In the overall cohort, a J-shaped association between BMI and in-hospital mortality was depicted. In the subgroup of men, BMI 35-39.9 kg/m2 and BMI ≥40 kg/m2 were found to have significant association with higher in-hospital mortality, while only BMI ≥40 kg/m2 was found significant in the subgroup of women. No significant association between BMI and IL-6 was noted. Obesity classes II and III in men and obesity class III in women were independently associated with higher in-hospital mortality in patients with COVID-19. The male population with severe obesity was the one that mainly drove this association. No significant association between BMI and IL-6 was noted.

Early and Significant Reduction in C-Reactive Protein Levels After Corticosteroid Therapy Is Associated With Reduced Mortality in Patients With COVID-19.

BACKGROUND: Corticosteroids may be beneficial in a subset of patients with coronavirus disease 2019 (COVID-19), but predictors of therapeutic response remain unknown. C-reactive protein (CRP) is a routinely measured biomarker, and reduction in its levels after initiation of therapy may predict inpatient mortality. METHODS: In this retrospective cohort study, the charts of patients who were admitted to Montefiore Medical Center between March 10, 2020, and May 2, 2020 for the management of COVID-19 were examined. Of all patients who met inclusion criteria, patients who received corticosteroid treatment were categorized as CRP responders (≥50% CRP level reduction) and CRP nonresponders (<50% CRP level reduction) based on change in CRP within 72 hours of corticosteroid treatment initiation. The outcomes of interest were two-fold: (1) CRP response after treatment with corticosteroid, and (2) differences in mortality among patients with CRP response compared those without. RESULTS: Of 2,707 patients admitted during the study period, 324 received corticosteroid treatment. Of patients who received corticosteroid treatment, CRP responders had reduced risk of death compared with risk among CRP nonresponders (25.2% vs 47.8%; unadjusted odds ratio [OR], 0.37; 95% CI, 0.21-0.65; P <.001). This effect remained strong and significant after adjustment for potential confounders (adjusted OR, 0.27; 95% CI, 0.14-0.54; P <.001). CONCLUSION: Reduction in CRP by 50% or more within 72 hours of initiating corticosteroid therapy potentially predicts inpatient mortality. This may serve as an early biomarker of response to corticosteroid therapy in patients with COVID-19.

Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients.

OBJECTIVE: To explore the possible associations of serum 25-hydroxyvitamin D [25(OH)D] concentration with coronavirus disease 2019 (COVID-19) in-hospital mortality and need for invasive mechanical ventilation. PATIENTS AND METHODS: A retrospective, observational, cohort study was conducted at 2 tertiary academic medical centers in Boston and New York. Eligible participants were hospitalized adult patients with laboratory-confirmed COVID-19 between February 1, 2020, and May 15, 2020. Demographic and clinical characteristics, comorbidities, medications, and disease-related outcomes were extracted from electronic medical records. RESULTS: The final analysis included 144 patients with confirmed COVID-19 (median age, 66 years; 64 [44.4%] male). Overall mortality was 18%, whereas patients with 25(OH)D levels of 30 ng/mL (to convert to nmol/L, multiply by 2.496) and higher had lower rates of mortality compared with those with 25(OH)D levels below 30 ng/mL (9.2% vs 25.3%; P=.02). In the adjusted multivariable analyses, 25(OH)D as a continuous variable was independently significantly associated with lower in-hospital mortality (odds ratio, 0.94; 95% CI, 0.90 to 0.98; P=.007) and need for invasive mechanical ventilation (odds ratio, 0.96; 95% CI, 0.93 to 0.99; P=.01). Similar data were obtained when 25(OH)D was studied as a continuous variable after logarithm transformation and as a dichotomous (<30 ng/mL vs ≥30 ng/mL) or ordinal variable (quintiles) in the multivariable analyses. CONCLUSION: Among patients admitted with laboratory-confirmed COVID-19, 25(OH)D levels were inversely associated with in-hospital mortality and the need for invasive mechanical ventilation. Further observational studies are needed to confirm these findings, and randomized clinical trials must be conducted to assess the role of vitamin D administration in improving the morbidity and mortality of COVID-19.

Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients.

PURPOSE: Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. The aim of this study was to systematically review and conduct a meta-analysis of the available observational studies reporting the effect of diabetes on mortality among hospitalized patients with COVID-19. METHODS: The Medline, Embase, Google Scholar, and medRxiv databases were reviewed for identification of eligible studies. A random effects model meta-analysis was used, and I2 was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed. RESULTS: A total of 18,506 patients were included in this meta-analysis (3713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared with patients without diabetes (OR 1.65; 95% CI 1.35-1.96; I2 77.4%). The heterogeneity was high. A study-level meta-regression analysis was performed for all the important covariates, and no significant interactions were found between the covariates and the outcome of mortality. CONCLUSION: This meta-analysis shows that that the likelihood of death seems to be higher in diabetic patients hospitalized with COVID-19 compared with non-diabetic patients. Further studies are needed to assess whether this association is independent or not, as well as to investigate the role of adequate glycemic control prior to infection with COVID-19.

Venous thromboembolism in the era of COVID-19.

Coronavirus disease 2019 (COVID-19) does not only affect the respiratory system but appears to be a systemic disease. Venous thromboembolism is a common manifestation in hospitalized patients with COVID-19 with a reported incidence that is significantly higher compared to other acute viral infections. The pathophysiology mechanisms have not been fully explored and autopsy studies might enhance our understanding on this topic. Microthrombi formation occurs mainly in the pulmonary vasculature but can also occur in other organs. The high inflammatory burden related to COVID-19 seems to be associated with the coexisting coagulopathy. Concomitant manifestations of COVID-19, such as severe pneumonia, which has similar clinical presentation with pulmonary embolism (PE), and barriers related to strict isolation protocols are the two main reasons why PE diagnosis might be more challenging in patients with COVID-19. Medical societies have published guidance reports suggesting the administration of prophylactic anticoagulant therapy in hospitalized patients with COVID-19, but several questions regarding the optimal acute and long-term treatment of these patients remain unanswered.

Severe obesity is associated with higher in-hospital mortality in a cohort of patients with COVID-19 in the Bronx, New York

Background & Aims New York is the current epicenter of Coronavirus disease 2019 (COVID-19) pandemic. The underrepresented minorities, where the prevalence of obesity is higher, appear to be affected disproportionately. Our objectives were to assess the characteristics and early outcomes of patients hospitalized with COVID-19 in the Bronx and investigate whether obesity is associated with worse outcomes independently from age, gender and other comorbidities. Methods This retrospective study included the first 200 patients admitted to a tertiary medical center with COVID-19. The electronic medical records were reviewed at least three weeks after admission. The primary endpoint was in-hospital mortality. Results 200 patients were included (female sex: 102, African American: 102). The median BMI was 30 kg/m2. The median age was 64 years. Hypertension (76%), hyperlipidemia (46.2%), and diabetes (39.5%) were the three most common comorbidities. Fever (86%), cough (76.5%), and dyspnea (68%) were the three most common symptoms. 24% died during hospitalization (BMI<25 kg/m2: 31.6%, BMI 25-34 kg/m2: 17.2%, BMI≥35 kg/m2: 34.8%, p= 0.03). Increasing age (analyzed in quartiles), male sex, BMI≥35 kg/m2 (reference: BMI 25-34 kg/m2), heart failure, CAD, and CKD or ESRD were found to have a significant univariate association with mortality. The multivariate analysis demonstrated that BMI≥35 kg/m2 (reference: BMI 25-34 kg/m2, OR: 3.78;95% CI: 1.45 - 9.83;p=0.006), male sex (OR: 2.74;95% CI: 1.25 - 5.98;p=0.011) and increasing age (analyzed in quartiles, OR: 1.73;95% CI: 1.13 - 2.63;p=0.011) were independently associated with higher in-hospital mortality. Similarly, age, male sex, BMI≥35 kg/m2 and current or prior smoking were significant predictors for increasing oxygenation requirements in the multivariate analysis, while male sex, age and BMI≥35 kg/m2 were significant predictors in the multivariate analysis for the outcome of intubation. Conclusions In this cohort of hospitalized patients with COVID-19 in a minority-predominant population, severe obesity, increasing age, and male sex were independently associated with higher in-hospital mortality and in general worse in-hospital outcomes.