ABSTRACT
Background: Immune reconstitution inflammatory syndrome (IRIS) is a rapid inflammatory response with immune recovery, most commonly observed following antiretroviral therapy initiation in people with HIV and underlying opportunistic infections. To date there is one reported case of COVID-associated IRIS in a neutropenic patient treated with granulocyte colony-stimulating factor (G-CSF). Here we describe a second case of COVID-associated IRIS in a patient with history of follicular lymphoma who received G-CSF during acute COVID-19 infection. Case: A 64-year-old woman with history of follicular lymphoma and autologous stem cell transplant one year prior presented with dyspnea, diarrhea, and fever, and tested positive for SARS-CoV-2. She had received three doses of the Pfizer BioNTech vaccine. She was admitted to the hospital for acute hypoxic respiratory failure and treated with remdesivir 100mg, dexamethasone 6mg, and 2 L/min supplemental oxygen via nasal cannula for five days. Twelve days after discharge, the patient returned with persistent diarrhea, fatigue, fever, and an oxygen saturation of 87% on room air. She again tested positive for SARS-CoV-2 by PCR. She was admitted to the intensive care unit for high-flow nasal cannula (HFNC) with oxygen at 30 L/min and 50% FiO2 and treated with methylprednisolone 1 mg/kg daily. On admission, her D-dimer was 3943 ng/mL, C-reactive protein 136 mg/L, absolute neutrophil count (ANC) 767/mcL, platelets 84/mcL. Her chest CT scan was negative for pulmonary embolism but demonstrated bilateral ground glass opacities characteristic of COVID-19 pneumonia. Her ANC reached a nadir of 186 on day 3 at which point G-CSF (filgrastim 300 mcg/day) was administered for three days with subsequent neutrophil recovery. On day 6, in light of a negative test for COVID antibodies, she received high-dose monoclonal antibodies through a compassionate use program. At that time, her oxygen requirements were stable and inflammatory markers had decreased to CRP 25 and D-Dimer 940. However, her oxygen requirements and inflammatory markers rapidly increased thereafter, with HFNC settings up to 60L/80%, D-dimer 27754, and CRP 135. After a repeat chest CT on day 8 showed worsened ground glass opacities throughout all lung fields, her steroid dose was increased to methylprednisolone 2 mg/kg daily out of concern for COVID-associated IRIS following G-CSF administration. Her oxygen requirement and inflammatory markers declined over the following 2-3 days and she was transferred out of the ICU. Discussion: We present here an unusual case of COVID-associated IRIS after G-CSF administration in a transplant patient with COVID-19 pneumonia. Given the increased risk of infection and severe illness in immunosuppressed patients despite vaccination, it is important for providers to be aware of complications associated with adjunct therapies such as G-CSF in this vulnerable population.
ABSTRACT
Background. Measuring SARS-CoV-2 antibody prevalence in spent samples at serial time points can determine seropositivity in a diverse pool of individuals to inform understanding of trends as vaccinations are implemented. Methods. Blood samples collected for clinical testing and then discarded ("spent samples") were obtained from the clinical laboratory of a medical center in Atlanta. A convenience sample of spent samples from both inpatients (medical/surgical floors, intensive care, obstetrics) and outpatients (clinics and ambulatory surgery) were collected one day per week from January-March 2021. Samples were matched to clinical data from the electronic medical record. In-house single dilution serological assays for SARSCoV-2 receptor binding domain (RBD) and nucleocapsid (N) antibodies were developed and validated using pre-pandemic and PCR-confirmed COVID-19 patient serum and plasma samples (Figure 1). ELISA optical density (OD) cutoffs for seroconversion were chosen using receiver operating characteristic analysis with areas under the curve for all four assays greater than 0.95 after 14 days post symptom onset. IgG profiles were defined as natural infection (RBD and N positive) or vaccinated (RBD positive, N negative). Single dilution serological assays for SARS-CoV-2 nucleocapsid antibodies were validated using pre-pandemic and PCR-confirmed COVID-19 patient serum and plasma samples. ELISA optical density (OD) cutoffs for seroconversion were chosen using receiver operating characteristic (ROC) analysis with areas under the curve (AUC) for all four assays greater than 0.95 after 14 days post symptom onset. Results. A total of 2406 samples were collected from 2132 unique patients. Median age was 58 years (IQR 40-70), with 766 (36%) ≥ 65 years. The majority were female (1173, 55%), and 1341 (63%) were Black. Median Elixhauser comorbidity index was 5 (IQR 2-9). 210 (9.9%) patients ever had SARS-CoV-2 detected by PCR, and 191 (9.0%) received a COVID-19 vaccine within the health system. Nearly half (1186/2406, 49.3%) of samples were collected from inpatient units, 586 (24.4%) from outpatient labs, 403 (16.8%) from the emergency department, and 231 (9.6%) from infusion centers. Overall, 17.0% had the IgG natural infection profile, while 16.2% had a vaccination profile. Prevalence estimates for IgG due to natural infection ranged from 24.0% in week 2 to 9.7% in week 5, and for IgG due to vaccine from 4.4% in week 2 to 32.0% in week 6 (Table, Figure 2). Conclusion. Estimated SARS-CoV-2 IgG seroprevalence among patients at a medical center from January-March 2021 was 17% by natural infection, and 16% by vaccination. Weekly trends likely reflect community spread and vaccine uptake.
ABSTRACT
Purpose : Coronavirus disease (COVID-19) has escalated to a global pandemic with increasing reports of ophthalmic disease. We report ophthalmic observations of hospitalized COVID-19 patients and correlate retinal disease findings with clinical and laboratory data. Methods : Retrospective review of COVID-19 patients who underwent ophthalmic exam during hospitalization within Emory Healthcare between April-July 2020. Results : Thirty-seven patients were examined with 23 (62%) females and a mean age of 54 years. 35 patients were admitted to the ICU. Ophthalmic manifestations included conjunctival injection in 12 eyes (17%), chemosis in 8 (11%) and retinopathy in 20 eyes (27%) with bilateral retinopathy in 6 patients (16%). No difference in baseline comorbidities or COVID-19 complication development was observed between patients with and without retinopathy. However, patients with retinopathy required ICU care for 1 week longer than those without retinopathy (27.6 vs 19.9 days p=0.19). The mean sequential organ failure assessment score at ICU admission was 6.18. All patients with retinopathy required both mechanical ventilation and vasopressors, while in patients without retinopathy, 15 (65%) and 12 (52%) required mechanical ventilation and vasopressors respectively (p=0.015, p=0.002). 6 patients with retinopathy required extracorporal membrane oxygenation compared to 1 without retinopathy (p=0.0070). While the mean peak D-Dimer was elevated at 18477, in the entire cohort, the peak D-Dimer was higher in patients with retinopathy (28,971 vs 12,575, p=0.0298). The fibrinogen nadir during hospitalization was on average 338 for the entire cohort, and reduced in patients with retinopathy (262 vs 381, p=0.029). Peak D-dimer analyses with a threshold of 16,508 showed an odds ratio of 16.7 (95% CI 3.11-89.3) for retinopathy. Fibrinogen nadir with a threshold of 367 showed odds ratio of 0.06 (95% CI 0.01-0.53) with 0.75 concordance. Conclusions : Retinopathy was the most common ophthalmic manifestation in a critically ill COVID-19 population, exceeding 25% of patients. Elevated D-dimers and a lower fibrinogen nadir in patients with retinopathy suggest a pathogenic relationship between coagulation pathways and retinal microangiopathy.
ABSTRACT
Introduction: COVID-19 has been associated with venous and arterial thrombotic complications. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events. Methods: COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer). For this analysis we excluded patients on outpatient anticoagulation therapy preceding admission. Prespecified endpoints monitored during hospitalization included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke and access line thrombosis. Results: During the study period, 276 patients were included in the analysis cohort (mean age 59 ± 6.3 years, 47% female, 83% non-white race). Arterial and venous thrombotic events occurred in 43 (16%) patients (see Table). Each coagulation marker was independently associated with the composite endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities was associated with the composite endpoint (OR 3.1, 95% CI 1.2-8.3), ICU admission (OR 3.2, 95% CI 1.8-5.5) and intubation (OR 2.8, 95% CI 1.5-5.5). Admission MOCHA with < 2 abnormalities (26% of the cohort) had sensitivity of 88% and a negative predictive value of 93% for an in-hospital endpoint. Conclusion: Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at risk for a thrombotic event, ICU admission and intubation while < 2 abnormalities identified a subgroup of patients who were at low risk for thrombotic events. Our results suggest that an admission MOCHA profile can be useful to risk stratify COVID-19 patients. Further studies are needed to determine whether an admission MOCHA profile can guide anticoagulation therapy and improve overall clinical outcomes.(Figure Presented).