Corrigendum: D-dimer trends elaborate the heterogeneity of risk in hospitalized patients with COVID-19: a multi-national case series from different waves.

[This corrects the article DOI: 10.3389/fmed.2023.1103842.].

D-dimer trends elaborate the heterogeneity of risk in hospitalized patients with COVID-19: A multi-national case series from different waves.

Introduction: Variable D-dimer trends during hospitalization reportedly result in distinct in-hospital mortality. In this multinational case series from the first and second waves, we show the universality of such D-dimer trends. Methods: We reviewed 405 patients with COVID-19 during the first wave admitted to three institutions in the United States, Italy, and Colombia, and 111 patients admitted to the U.S. site during the second wave and 55 patients during the third wave. D-dimer was serially followed during hospitalization. Results: During the first wave, 66 (15%) patients had a persistently-low pattern, 33 (8%) had early-peaking, 70 (16%) had mid-peaking, 94 (22%) had fluctuating, 30 (7%) had late-peaking, and 112 (26%) had a persistently-high pattern. During the second and third waves, similar patterns were observed. D-dimer patterns were significantly different in terms of in-hospital mortality similarly in all waves. Patterns were then classified into low-risk patterns (persistently-low and early-peaking), where no deaths were observed in both waves, high-risk patterns (mid-peaking and fluctuating), and malignant patterns (late-peaking and persistently-high). Overall, D-dimer trends were associated with an increased risk for in-hospital mortality in the first wave (overall: HR: 1.73) and stayed the same during the second (HR: 1.67, p < 0.001) and the third (HR: 4.4, p = 0.001) waves. Conclusion: D-dimer behavior during COVID-19 hospitalization yielded universal categories with distinct mortality risks that persisted throughout all studied waves of infection. Monitoring D-dimer behavior may be useful in the management of these patients.

Association between right ventricular dysfunction and in-hospital mortality in surges of SARS-CoV-2 infection attributed to the Alpha, Delta, and Omicron variants.

Background: Right ventricular (RV) dysfunction in acute COVID-19 was reported to be associated with poor prognosis. We studied the association between parameters of RV dysfunction and in-hospital mortality during the surges caused by different SARS-CoV-2 variants. Methods: In a retrospective single-center study, we enrolled 648 consecutive patients hospitalized with COVID-19 [66 (10 %) hospitalized during the alpha variant surge, 433 (67 %) during the delta variant surge, and 149 (23 %), during the omicron variant surge]. Patients were reported from a hospital with an underreported population of mostly African American and Hispanic patients. Patients were followed for a median of 11 days during which in-hospital death occurred in 155 (24 %) patients [Alpha wave: 25 (38 %), Delta Wave: 112 (26 %), Omicron wave: 18 (12 %), p < 0.001]. Results: RV dysfunction occurred in 210 patients (alpha: 32 %, 26 %, delta: 29 %, and omicron: 49 %, p < 0.001) and was associated with higher mortality across waves, however, independently predicted in-hospital mortality in the Alpha (HR = 5.1, 95 % CI: 2.06-12.5) and Delta surges (HR = 1.6, 95 % CI: 1.11-2.44), but not in the Omicron surge. When only patients with RV dysfunction were compared, the mortality risk was found to decrease significantly from the Alpha (HR = 13.6, 95 % CI: 3.31-56.3) to the delta (HR = 1.93, 95 % CI: 1.25-2.96) and to the Omicron waves (HR = 11, 95 % CI: 0.6-20.8). Conclusions: RV dysfunction continues to occur in all strains of the SARS-CoV-2 virus, however, the mortality risk decreased from wave to wave likely due to evolution of better therapeutics, increase rate of vaccination, or viral mutations resulting in decrease virulence.Registration number of clinical studies: BronxCare Hospital center institutional review board under the number 05 13 21 04.

Outcomes of Monoclonal Antibody Infusion Treatment During Delta (B.1.617.2) and Omicron (B.1.1.529) COVID 19 Variant Surges among Vaccinated and Unvaccinated Patients.

Background: Coronavirus infection of 2019 (COVID-19) is associated with significant morbidity and mortality. Vaccines supplement public health and social measures in preventing severe illness and mortality from COVID-19; however, vaccination rates remain inadequate in many regions. It is important to continuously explore the effective treatment due to the insufficient vaccination rate and increasing number of patients infected with virus. The emergence of new variants has led to multiple surges throughout the world requiring changes to treatment protocols. Method: We conducted a single-center observational study on all adult patients who received monoclonal antibody (mAb) infusion as a treatment for COVID-19 infection. Based on the predominant variant, patients were either offered Casirivimab (600 mg)/imdevimab (600 mg) or Sotrovimab (500 mg). Forty-six patients were given mAbs; 24 were vaccinated, and the remaining unvaccinated. Result: The mean age was 56 years, and the majority (63.04%) of the patients were female. Clinical symptoms of COVID-19 improved within 3 days of infusion in the majority of the patients (70%). None of the patients who received mAb showed progression of disease or required hospitalization at 30 days follow-up. There were no deaths at 30 days follow-up. Monoclonal antibodies are highly effective in reducing hospitalizations and mortality when given within 7 days of symptoms onset in patients with high-risk factors for progression to severe COVID-19 infection. The mean number of days after the onset at which the mAbs were administered to the patient was 4. Conclusion: Monoclonal antibodies should be considered in both vaccinated and unvaccinated patients with COVID-19 infection if newer antiviral agents are contraindicated. Our study highlights the effectiveness of monoclonal antibody infusions when given early in the course of COVID-19 infection regardless of vaccination status.

Role of body mass index in outcomes of patients hospitalized with COVID-19 illness.

Background: Since the start of coronavirus disease 2019 (COVID-19) pandemic, several studies have linked obesity with severity of illness as well as mortality in patients with COVID-19. Outcomes of patients with overweight or obesity, who develop critical illness, have been studied extensively over the past decade where the studies have shown conflicting results. In this study, we aimed to assess the association between the body mass index (BMI) classes and outcomes among hospitalized patients with COVID-19. Methods: This was a retrospective chart review of all adults admitted to our hospital with COVID-19 illness between 1 March 2020 and 30 June 2020. Patients were divided into four groups based on their BMI range as follows: patients with underweight (BMI < 18.5 kg/m2), patients with normal weight (BMI 18.5-24.9 kg/m2), patients with overweight (BMI 25-29.9 kg/m2), and patients with obesity (BMI ≥ 30 kg/m2). Results: 1274 patients were admitted during the study period. There were 24 (1.9%) patients with underweight, 268 (21%) patients with normal weight, 445 (34.9%) patients with overweight, and 537 (42.2%) patients with obesity. Patients with obesity were younger (p < 0.001) and there were more females among patients with underweight and patients with obesity (54% and 48% respectively, p < 0.001). There were no differences in subgroup with regards to presence of hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, and dyslipidemia. In a multivariate logistic regression model, patients with overweight and patients with obesity had higher odds of requiring mechanical ventilation. BMI class was not associated with difference in survival time in a multivariate analysis. Conclusions: In our large single-center study of hospitalized patients with COVID-19, patients with overweight and obesity had higher need for mechanical ventilation but had similar mortality when compared to patients with normal weight and underweight.

A High-Risk Patient With COVID-19 Vaccine Hesitancy Successfully Treated With Monoclonal Antibodies Through Two Major Surges.

Vaccine hesitancy remains a significant challenge in managing the current pandemic despite highly effective vaccines in the United States. Monoclonal antibodies (mAb) are an essential addition to coronavirus disease 2019 (COVID-19) treatment, along with oral antiviral agents (OAA), for non-hospitalized patients having risk factors for progression to severe COVID-19, especially in unvaccinated people. We present a case of a 74-year-old unvaccinated Hispanic woman with a history of diabetes mellitus, hypertension, coronary artery disease, obesity, and asthma who survived two episodes of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infections in January 2021 and December 2021 with exclusive use of mAb. Our case highlights the importance of using mAbs for treating high-risk patients with SARS-CoV-2 infection, especially in patients with vaccine hesitancy.

A Rare Case of Coronavirus Disease 2019 Vaccine-Associated Cerebral Venous Sinus Thrombosis Treated with Mechanical Thrombectomy.

BACKGROUND Vaccine-related thrombosis and thrombocytopenia syndrome (TTS) is a rare life-threatening syndrome reported after vaccination against COVID-19. CASE REPORT We describe a case of 56-year-old postmenopausal, obese woman with hypothyroidism and hyperlipidemia, who presented to the Emergency Department (ED) with fluctuating mental status and left-side weakness for 5 days. She received her first and second dose of mRNA-1273 vaccine (Moderna) at 12 and 8 weeks, respectively, prior to presentation. She was found to have multiple hemorrhages and infarcts on a computed tomography (CT) scan of the head. She was intubated in the ED for airway protection and mechanically ventilated. Magnetic resonance angiogram and venogram showed multiple infarcts in right frontal, parietal, and left parietal lobes, along with occlusion of left-side transverse sinus, sagittal sinuses, and left internal jugular vein, suggesting cerebral venous sinus thrombosis (CVST). Despite anticoagulation, her clinical condition continued to worsen, and she was referred for emergent endovascular thrombectomy. Her clinical condition improved after thrombectomy, and she was discharged on warfarin. At 4-month follow-up, she was able to walk with an assistive device and able to carry out activities of daily living with assistance. She is planned for further work-up for hypercoagulable state at follow-up. CONCLUSIONS This case highlights the occurrence of vaccine-related thrombosis 3 months after vaccine administration. Only 2 cases of TTS have been reported so far after mRNA-1273 vaccination (Moderna). To the best of our knowledge, this is the first reported case of CVST presenting 3 months after the first dose of COVID-19 mRNA-1273 vaccine (Moderna).

Use of Monoclonal Antibodies Therapy for Treatment of Mild to Moderate COVID-19 in 4 Patients with Rheumatologic Disorders.

BACKGROUND The use of monoclonal antibodies therapy (MAT) in early mild to moderate Coronavirus disease 2019 (COVID-19) has gained importance in recent times. However, there is limited information on the safety and efficacy of MAT in treating COVID-19 in patients with underlying rheumatologic diseases. Patients with rheumatologic diseases are usually on long-term corticosteroids and immunosuppressive therapy, which increases their risk for progressing to more severe forms of COVID-19. We report a case series of 4 patients with rheumatologic diseases who were treated with MAT for COVID-19. MATERIAL AND METHODS A retrospective observational study was conducted in our institution on patients with underlying rheumatological disorders who received MAT as per the EUA protocol of the FDA. RESULTS Two of the 4 patients were on immunosuppresive therapy at the time of receiving MAT. They recovered from COVID-19 without any adverse outcomes. No flare of underlying rheumatologic disease was noted. CONCLUSIONS MAT was observed to be a safe and effective therapy in 4 patients with rheumatological illnesses and COVID-19 treated at our hospital.

Chronic hepatitis-C infection in COVID-19 patients is associated with in-hospital mortality.

BACKGROUND: There is little evidence about the association of pre-existing hepatitis C infection (HCV) with outcomes in patients with coronavirus disease 2019 (COVID-19). AIM: To assess the prevalence of history of HCV among patients with COVID-19 and to study the relationship of in-hospital mortality in relation with other predictors of poor outcomes in the presence or absence of COVID-19 induced acute liver injury. METHODS: In a retrospective single-center study design, 1193 patients with COVID-19 infection were studied. Patients were then classified into those with and without a history of HCV, 50 (4.1%) and 1157 (95.9%) respectively. RESULTS: Multivariate cox-regression models showed that age, HCV, D-Dimer, and ferritin were the only predictors of in-hospital mortality. Acute liver injury and fibrosis score (Fib-4 score) were not different between both groups. Multivariate cox-regression model for liver profile revealed that aspartate aminotransferase/ alanine aminotransferase ratio, Fib-4 score, and HCV were predictors of in-hospital mortality. After propensity score matching HCV was the only predictor of mortality in the multivariate cox-regression model. A model including HCV was found to add predictive value to clinical and laboratory parameters. CONCLUSION: In patients with COVID-19, history of HCV infection leads to an accentuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virulence, irrespective of baseline comorbidities, admission laboratory variables, or COVID-19-induced liver injury, which may be related to extrahepatic effects of HCV leading to enhanced ACE-2/TMPRSS mechanisms of SARS-CoV-2 viral entry, baseline cytokine-mediated pro-inflammation, and endothelial dysfunction.

The Incidence and Mortality Impact of Gastrointestinal Bleeding in Hospitalized COVID-19 Patients.

BACKGROUND: Patients requiring hospitalization to critical care units are at a higher risk for gastrointestinal (GI) bleeding. Although severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is predominantly a pulmonary disease, other serious manifestations including thromboembolic phenomenon are reported. Acute respiratory distress syndrome (ARDS) requiring mechanical ventilation, use of steroids and anticoagulation are all known to increase the risk of GI bleeding significantly. AIM: To study the incidence of GI bleeding and its impact on mortality in patients admitted with SARS-CoV-2. METHODS: We retrospectively reviewed all patients admitted with SARS-CoV-2 from February 1, 2020 to April 15, 2020. We collected data including demographics, comorbid conditions, laboratory parameters, steroid and anticoagulant use. Coffee ground emesis, hematemesis, melena and hematochezia were defined as GI bleeding. All-cause mortality was reviewed for all patients included in the study. The relationship between GI bleeding and mortality was studied using logistic regression. RESULTS: We had a total of 1206 patients hospitalized with SARS-CoV-2 infection with an all-cause mortality of 34% (n = 411). The overall incidence of GI bleeding was 3.1% (n = 37) with no significant difference between the patients who survived versus died during hospitalization (1.3% vs 1.5%, p = 0.77). Logistic regression analysis did not identify GI bleeding as an independent predictor of mortality. Therapeutic doses of anticoagulation were administered in 13.3% (n = 161) of patients, of which 6.8% (n = 11) developed GI bleeding. Patients were more likely to develop GI bleeding with use of therapeutic doses of anticoagulation (29.7% vs 12.8%, p = 0.003), steroids (37.8% vs 18.5%, p = 0.003) and mechanical ventilation (48.6% vs 30.4%, p = 0.018). CONCLUSION: Patients hospitalized with SARS-CoV-2 infection are at risk of gastrointestinal bleeding. Therapeutic doses of anticoagulation, mechanical ventilation and steroid use are significant risk factors for GI bleeding. However, GI bleeding did not significantly alter the mortality rates in SARS-CoV-2-infected patients.

Anticoagulation for hypercoagulability in severe critical COVID-19: A case series of fading and fatal cycles of microthrombosis.

The pathophysiology of the COVID-19 involves a systemic hypercoagulable state and systemic micro-thrombosis which can cause fatal consequences. Despite that anticoagulation seems an intuitive therapeutic option, the US National Institute of Health has issued a warning against its use in critically ill patients. We present five cases of imaging-proven or clinically suspected hypercoagulability with hemodynamic compromise despite therapeutic anticoagulation. We describe the patients with thoughts on links between pathophysiology and the laboratory values, clinical course, and imaging studies in each case. All patients presented to the hospital with symptoms and chest imaging suggestive of COVID-19 pneumonia. All patients presented with severe hypoxia requiring mechanical ventilation, and received full anticoagulation for treatment of hypercoagulable state suggested by elevated D-dimer. All but one patient received alteplase for thrombolytic therapy of suspected massive pulmonary embolism (PE). On the basis of this case series, hypercoagulability in COVID-19 is a late manifestation of the disease that persists despite anticoagulation, is cyclic in nature based on D-dimer despite thrombolysis, and is fatal if it rebounds. The use of anticoagulation and thrombolysis in these patients seemed harmful or non-beneficial. Early intervention before D-dimer elevation and hemodynamic compromise may benefit in preventing thromboembolic burden. .

Implementation and outcomes of monoclonal antibody infusion for COVID-19 in an inner-city safety net hospital: A South-Bronx experience.

BACKGROUND: Monoclonal antibody therapy (MAT) is recommended in mild to moderate Coronavirus disease 2019 (COVID-19) patients who are at risk of progressing to severe disease. Due to limited data on its outcomes and the logistic challenges in administering the drug, MAT has not been widely used in the United States (US) despite of emergency use authorization (EUA) approval by the Food and Drug Administration (FDA). AIM: We aim to study the outcomes of MAT in patients predominantly from ethnic minority groups and the challenges we experienced in implementing the infusion therapy protocol in an inner-city safety-net-hospital in the South Bronx. METHODS AND RESULTS: We conducted a retrospective observational study of 49 patients who were offered MAT as per EUA protocol of FDA. Patient who met the criteria for MAT and received therapy were included in treatment group (n = 38) and the remaining (n = 11) who declined treatment were included in the control group. A majority of patients (76%) in the study group reported symptomatic improvement, the day after infusion. There was statistically significant reduction in COVID-19 related hospitalizations (7.8 vs 54.5%, P = < 0.001) mortality (0 vs 18.1%, P value = 0.008) in the treatment group. CONCLUSION: MAT reduced both hospitalization and mortality in this predominantly Hispanic patient population with mild to moderate COVID-19 with high risk factors for disease progression.

BNT162b2 mRNA Vaccine Interference with Co-Administration of Tdap Vaccine.

BACKGROUND It is unknown if the efficacy of the coronavirus disease-19 (COVID-19) vaccine is affected by the co-administration of other vaccines. The Centers for Disease Control and Prevention (CDC) has shifted their recommendations recently, allowing for the co-administration of the currently available COVID-19 vaccines with other vaccines. This is based on the experience with non-COVID-19 vaccines, where the immunogenicity and adverse event profiles were generally similar when vaccines are administered simultaneously or alone. CASE REPORT We present a case of a 29-year-old Asian woman who received the first dose of BNT162b2 mRNA vaccine and the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine at around the same time. BNT162b2 mRNA vaccine and Tdap vaccine were administered into the deltoid region of the left arm and right arm, respectively. We then monitored for immunogenicity. We observed a delay in the development of SARS-CoV-2 Spike (S1) protein antibodies at around 8 weeks after the second dose. CONCLUSIONS Unless warranted, it is important to adhere to current CDC recommendations with regards to the co-administration of vaccines. Although the administration of Tdap with COVID-19 vaccine in our case caused delay in immunogenicity, it did not negate the ability of the BNT162B2 mRNA vaccine to elicit an adequate immune response. The reason for delay in immune response with co-administration of COVID-19 vaccines with other vaccines is unknown and further studies are needed.

Potential predictors of outcomes among hospitalized COVID-19 patients treated with convalescent plasma: a single-center study.

Background: The coronavirus disease 2019 pandemic is a major international public health crisis, which has led to over 3 million deaths as of April 2021. Several therapeutics have been tried for this deadly illness including antivirals, immunosuppressive agents and convalescent plasma (CP). In this study, we present our inner-city safety net hospital experience with CP therapy. Methods: This was a retrospective chart review of hospitalized patients with confirmed COVID-19 who were treated with CP. Results: A total of 60 patients received CP during the study period. The mean age for patients in this study was 58.95 years. The most common presenting symptoms were shortness of breath (85%) and cough (73%). Hypertension (65%) and diabetes mellitus (55%) were the most common comorbidities in our patients. In our multivariate regression analysis, male sex, nausea and loss of appetite at presentation were associated with improvement in oxygenation after CP. Total survival time, history of obstructive airway disease, home use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers were associated with decreased survival, whereas Hispanic ethnicity showed a trend towards lower survival after CP therapy. Conclusions: Our study highlights several important characteristics of inner-city safety net hospital patient population who might benefit from CP therapy.

Impact of Prediabetes and Type-2 Diabetes on Outcomes in Patients with COVID-19.

INTRODUCTION: The true impact of prediabetes and type-2 diabetes in patients with COVID-19 remains unknown, with studies thus far providing conflicting evidence. METHODS: This is a single-center retrospective observational study involving 843 hospitalized patients with SARS-CoV-2 infection. Primary outcomes, mortality, and mechanical ventilation use were compared among the three groups: control, prediabetes, and type-2 diabetes. Binomial regression analysis was used to determine predictors of mortality and mechanical ventilation requirement. RESULTS: Age was a significant predictor of mortality. On stratifying our patients based on their age, older patients aged 55 years and above had no difference in mortality or mechanical ventilation requirement among the three groups of control, prediabetes, and type-2 diabetes. However, among the younger population aged less than 55 years, patients with type-2 diabetes had significantly higher mortality as compared with patients in control and prediabetes groups (27% vs 12.5% vs 9%, p 0.025). Additionally, newly diagnosed type-2 diabetes patients demonstrated lower mortality rate in comparison to previously known type-2 diabetes patients (18% vs 40%, p 0.005). Outcomes in the prediabetes group were similar to that in the control group. Admission hyperglycemia was associated with higher mortality regardless of diabetes status. CONCLUSION: In older patients aged 55 years and above, status of type-2 diabetes does not influence their mortality. However, in younger patients aged less than 55 years, the presence of type-2 diabetes is an important driver of mortality. Newly diagnosed type-2 diabetes, in comparison with previously diagnosed type-2 diabetes, may have better survival. Presence of prediabetes did not affect outcomes in patients with COVID-19 infection.

Diarrhea due to SARS-CoV-2-Related Exocrine Pancreatic Insufficiency.

Gastrointestinal symptoms, especially diarrhea, are common with novel coronavirus SARS-CoV-2 infection. Angiotensin-converting enzyme-2 (ACE-2) receptors are heavily expressed in enterocytes and serve as entry receptors for SARS-CoV-2. ACE-2 receptors may also be responsible for pancreatic injury in patients infected with SARS-CoV-2. Diarrhea associated with SARS-CoV-2 is usually believed to be due to viral invasion of enterocytes. However, exocrine pancreatic insufficiency resulting from SARS-CoV-2 is another plausible mechanism leading to diarrhea in such patients. We present a case series of three SARS-CoV-2-infected patients with predominant respiratory symptoms at presentation who developed diarrhea, and further fecal analysis revealed exocrine pancreatic insufficiency as the underlying mechanism.