COVID-19 Antibody Research Articles

Monoclonal antibodies that are effective against all COVID-19 -related viruses

All licensed COVID-19 antibody treatments become ineffective over time as new mutants emerge. We isolated antibodies from an individual who recovered from SARS-1 and received the COVID vaccine, that work against all COVID-related viruses including the latest Omicron variants. These broad-targeting antibodies could make future-proof therapeutics to counter the continual evolution of coronaviruses.

Timing of Maternal COVID-19 Vaccine and Antibody Concentrations in Infants Born Preterm

COVID-19 vaccine-derived antibodies in pregnant people may protect infants from severe infection in the first 6 months of life via transplacental antibody transfer. Few data exist on maternally derived SARS-CoV-2 antibodies in preterm compared with full-term infants in association with vaccination timing. To compare SARS-CoV-2 anti-Spike (anti-S) antibody levels in preterm and full-term infants in the context of vaccine dose timing before delivery. This prospective cohort study enrolled pregnant individuals and collected paired maternal and cord blood samples at delivery at the University of Washington between February 1, 2021, and January 31, 2023. Participants who had received at least 2 doses of a messenger RNA COVID-19 vaccine before delivery and did not have a history of prior COVID-19 infection or detectable anti-SARS-CoV-2 nucleocapsid antibodies were included. Timing of the last vaccine dose and preterm or full-term gestational age at delivery. Paired maternal and cord samples were tested for anti-S antibody, and linear regression was used to evaluate associations between preterm delivery and anti-S antibody levels. Covariates included timing of last dose, number of doses, insurance status, and immunosuppressing medications. A total of 220 participants (median [IQR] age, 34 [32-37] years; 212 [96.4%] female) with 36 preterm and 184 full-term deliveries were studied. Before delivery, 121 persons received 2 vaccine doses and 99 persons received 3 or more vaccine doses. The geometric mean concentration of maternal anti-S antibodies was 674 (95% CI, 577-787) after 2 doses and 8159 (95% CI, 6636-10 032) after 3 or more doses (P < .001). The cord anti-S antibody geometric mean concentration was 1000 (95% CI, 874-1144) after 2 doses and 9992 (95% CI, 8381-11 914) after 3 or more doses (P < .001). After adjustment for vaccine timing and number of doses before delivery, no association was found between preterm delivery and cord anti-S antibody levels (β = 0.44; 95% CI, -0.06 to 0.94). In this prospective cohort study of pregnant individuals with preterm and full-term deliveries, receipt of 3 or more compared with 2 doses of COVID-19 vaccine before delivery resulted in 10-fold higher cord anti-S antibody levels. Maternal antibody concentration appeared more important than delivery gestational age in determining cord anti-S antibody levels. The number of doses and timing considerations for COVID-19 vaccine in pregnancy should include individuals at risk for preterm delivery.

Further accelerating biologics development from DNA to IND: the journey from COVID-19 to non-COVID-19 programs.

The Coronavirus Disease (COVID-19) pandemic has spurred adoption of revolutionary initiatives by regulatory agencies and pharmaceutical industry worldwide to deliver therapeutic COVID-19 antibodies to patients at unprecedented speed. Among these, timeline of chemistry, manufacturing and control (CMC), which involves process development and manufacturing activities critical for the assurance of product quality and consistency before first-in-human clinical trials, was greatly reduced from typically 12-15months (using clonal materials) to approximately 3months (using non-clonal materials) in multiple cases. In this perspective, we briefly review the acceleration approaches published for therapeutic COVID-19 antibodies and subsequently discuss the applicability of these approaches to achieve investigational new drug (IND) timelines of ≤10months in over 60 COVID-19 and non-COVID-19 programs performed at WuXi Biologics. We are of the view that, with demonstrated product quality and consistency, innovative approaches used for COVID-19 can be widely applied in all disease areas for greater speed to clinic.

COVID-19 Antibody Levels among Various Vaccination Groups, One-Year Antibody Follow-Up in Two University Hospitals from Western and Central Turkey.

Various clinical outcomes, reinfections, vaccination programs, and antibody responses resulted from the COVID-19 pandemic. This study investigated the time-dependent changes in SARS-CoV-2 antibody responses in infected and/or vaccinated and unvaccinated individuals and to provide insights into spike and nucleocapsid antibodies, which fluctuate during infectious and non-infectious states. This cohort study was carried out at the Ege University Faculty of Medicine hospital in İzmir (western Turkey) and the Erciyes University Faculty of Medicine hospital in Kayseri (central Turkey) between December 2021 and January 2023, which coincided with the second half of COVID-19 pandemic. The study included 100 COVID-19 PCR-positive patients and 190 healthcare workers (HCWs). Antibody levels were followed up via quantitative anti-SARS-CoV-2 spike and qualitative anti-nucleocapsid immunoassays (Elecsys™). Antibody levels declined after infection but persisted for at least 6-8 months. Individuals who had received only CoronaVac had higher anti-nucleocapsid antibody levels in the early months than those who received mixed vaccination. However, anti-spike antibodies persisted longer and at higher levels in individuals who had received mixed vaccinations. This suggests that combining two different vaccine platforms may provide a synergistic effect, resulting in more durable and broad-spectrum immunity against SARS-CoV-2. The study provides information about the vaccination and antibody status of healthcare workers in the second half of the pandemic and provides valuable insights into the dynamics of antibody responses to COVID-19 infection and vaccination.

The Polk COVID-19 and Flu Response clinical trial: COVID-19 antibody positivity higher in Black EMS workers

This study reports on a countywide assessment of COVID-19 positivity among emergency medical services workers. Participants completed a short survey of demographic factors and co-morbidities prior to obtaining COVID-19 and influenza testing to analyze the prevalence of these two respiratory viruses that EMS workers, being the first on the scene, are at special risk for, especially in the early days of the pandemic. A total of 7% had a positive COVID-19 antibody test. Although Black EMS personnel only comprised 9% of the cohort, they were significantly more likely to test positive for COVID-19 (P=0.0012). Black race remained a statistically significant predictor in a multivariate model that included the age, sex, BMI, number of hours of direct patient contact, whether the medic was symptomatic, presence of co-morbidities and whether or not the medic had received a flu shot prior (P=0.0008, 95% CI 0.0621-0.2354). This clinical trial (NCT04682132) ) was registered at clinicaltrials.gov, a resource provided by the U.S. National Library of Medicine.

SARS-CoV-2 Antibody Prevalence in Unvaccinated Children and Change in Antibody Levels Between 2020-2022

After the declaration of the COVID-19 pandemic by the World Health Organization (WHO), various restrictions were implemented, and face-to-face education was suspended in schools. In some countries, COVID-19 vaccines emergency use authorization has been granted for the pediatric age group. This study aimed to investigate COVID-19 antibody level in children who have not been vaccinated against COVID-19. A total of 1,000 pediatric patients aged 0-12 years, unvaccinated against COVID-19, admitted to Necmettin Erbakan University Medical Faculty Hospital Pediatrics clinics with different symptoms between October 2020 and April 2022 were included in this study. SARS-CoV-2 S total antibody levels were tested by ELISA method from the sera samples of these children. Of the children included in the study, 535 (53.5%) were male and 465 (46.5%) were female. Anti-SARS-CoV-2 S total Ig positivity rates were 75.9% in girls and 78.5% in boys and the difference between them was not statistically significant (p&gt;0.05). When the anti-SARS-CoV-2 S total Ig positivity rates of children were evaluated according to years, 23 (43.4%) in 2020, 183 (60%) in 2021, and 567 (88.3%) in 2022 was found positive. The difference between antibody results by years was found to be statistically significant (p&lt;0.001). Median value of SARS-CoV-2 antibody levels of patients with positive antibody test in 2020 46 AU/ml (min 5, max: 214 AU/ml), in 2021 130 AU/ml (min:1, max: 250 AU/ml), and in 2022 it was found to be 250 AU/ml (min:1, max: 250 AU/ml). When the antibody levels of patients with anti-SARS-CoV-2 S Ig total positive were evaluated, the difference between years was found to be statistically significant (p&lt;0.05). In our study, it was determined that the rate of SARS-CoV-2 S total antibody positivity reached 90% in unvaccinated children aged 12 and younger. Determining the SARS-CoV-2 antibody status of children aged 12 and under who unvaccinated against COVID-19 in our country will both give information about immunization by natural immunity and will be effective in deciding and planning the need for COVID-19 vaccination for children.

Allogenic Stem Cell Transplantation and COVID-19 Antibodies: Mechanistic Insights and Recipient Concerns

Allogenic Stem Cell Transplantation and COVID-19 Antibodies: Mechanistic Insights and Recipient Concerns

Single ChAdOx1 nCoV-19 dose elicits stronger immune response in previously infected individuals than in SARS-CoV2 naive persons.

Current vaccines against COVID-19 effectively reduce morbidity and mortality and are vitally important for controlling the pandemic. Between December 2020 and February 2021, adenoviral vector vaccines such as ChAdOx1 (AstraZeneca-Oxford) were put in use. Recent reports demonstrate robust serological responses to a single dose of messenger RNA vaccines in individuals previously infected with SARS-CoV-2. We aimed to study the association between previous COVID-19 infection and antibody levels after a single dose of ChAdOx1 nCoV-19. This cross-sectional study was conducted on 657 individuals who were either convalescent or SARS-CoV-2 naive and had received one dose of ChAdOx1 (AstraZeneca). A questionnaire was used to collect data on age, sex, and self-reported history of COVID-19 infection. We then compared the average levels of immunoglobulin G (IgG) between the previously infected and COVID-19-naive participants. We compared the antibody responses of individuals with confirmed prior COVID-19 infection with those of individuals without prior evidence of infection. The mean antibody levels in those who reported no history of COVID-19 infection were substantially lower than in those who were previously infected, in both males and females. Sex-related differences were observed when we compared antibody levels between men and women. In males, anti-S IgG antibody levels were higher in those who had been previously infected (156.1 vs. 87.69 AU/mL, p = .009), compared with the same pattern was observed in females (113.5 vs. 90.69 AU/mL, p = .005). Previous COVID-19 infection is associated with higher levels of SARS-CoV-2 antibodies following ChAdOx1 (AstraZeneca) vaccination. Our finding supports the notion that a single dose of ChAdOx1 nCoV-19 administered post-SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen for previously infected individuals.

COVID-19-induced Neonatal Acute Aortic Thrombosis

Abstract Venous thromboembolism is a well-recognized, common complication of a severe COVID-19 disease. Arterial thrombosis is a less known complication, now being reported increasingly, mostly in the form of myocardial infarction and stroke, but acute aortic occlusion is infrequent. Neonatal acute aortic thrombosis as a sequelae of COVID-19 disease has far uncommon incidence with no literature-based evidence till date. A 10-day-old male child presented to the emergency department with informant being his mother with complaints of black discoloration of his right foot for 4 days noticed first on his toes. No history of trauma, no history of fever, and no history of umbilical artery catheterization at birth was noted. Birth history-full term normal vaginal delivery, small for gestational age baby, cried immediately after birth, birth weight – 2.45 kg with no additional birth events. No history of neonatal intensive care unit stay, immunized at birth. Baby was 3rd by order of birth with no congenital anomalies noted in previous siblings. On examination, the baby was alert, afebrile, heart rate – 138/min, blood pressure – 90/60 mmHg, and SpO2 98% on room air. Local examination of the right lower limb revealed black discoloration of the right lower limb from toes up to mid-calf, CRT-delayed in the right thigh (7 s), right femoral pulsations absent, left lower limb – pink, warm, CRT – 6 s, feeble pulsations of left femoral artery and popliteal artery, absent pulsations of left anterior tibial artery, and posterior tibial artery. A Doppler study revealed the presence of partial lumen occluding thrombus (hyperechoic) in abdominal aorta below the level of renal arteries, absent flow in right lower limb, and monophasic flow in left femoral artery. A prothtrombotic screen was performed and COVID-19 antibody test was found to be positive. A systemic thrombolysis with injection reteplase was performed which showed mild improvement in circulation with propagation of clot up to origin of superior mesentric artery on a Doppler scan. An abdominal aortic embolectomy was performed, with retrieval of a long segment thrombus from distal abdominal aorta and bilateral femoral arteries following good proximal inflow and good distal backflow. Bilateral limb perfusion improved postoperatively though the gangrenous right lower limb could not be saved and a right below knee amputation was performed for the same. This case adds to the growing list of potential sites and consequences of thrombosis in COVID-19 infection. We speculate that this case of aortic thrombosis was a result of direct COVID-19-induced vascular damage in the context of a hypercoagulable state with a possibility of vertical transmission of the disease.

Evaluation of COVID-19 antibody levels in emergency department healthcare workers

Evaluation of COVID-19 antibody levels in emergency department healthcare workers

COVID-19-Associated Neurological Complications in Children.

Neurological manifestations of Severe Acute Respiratory Syndrome coronavirus-2 have been well documented in adults during and after infection with the virus as well as after vaccination. The incidence of severe neurological symptoms among children is very low. This study aimed to analyze the varied neurological manifestations after COVID-19 infection among children and give a report on a single-center experience with these severe neurological symptoms. Case records of patients less than 18 years admitted between July 2021 to December 2022 with neurological manifestations and COVID-19 infection or with elevated COVID-19 antibodies after exclusion of other etiological diagnosis were analyzed. There were 10 cases in the age range of 1-15 years. All the cases had elevated COVID-19 antibodies with history of contact 2-3 weeks prior except one who was positive for COVID-19 infection. Two cases presented with acute ascending paralysis suggestive of Guillain-Barre syndrome. Four cases presented with features of encephalopathy with clinical presentation fulfilling the criteria of Multisystem inflammatory syndrome in children. One case presented with fever and focal seizures with MRI showing sagittal sinus thrombosis, and one presented with fever and altered sensorium with MRI showing leukoencephalopathy. One child had cerebral mucormycosis without any evidence of immunosuppression. There was one child with features of encephalopathy with active COVID-19 infection. The varied presentation highlights the central and peripheral nervous system involvement by the virus in the pediatric population. It also emphasizes the need to investigate for COVID-19 in children presenting with these complaints during the pandemic.

Elevated Interleukin-6 (IL-6) Levels with Ig (G &amp; M) Antibodies in the Recovery Phase of Patients with COVID-19: Indication of Cytokine Storm and Re-infection

The innate immune response to coronavirus disease (COVID-19) by inflammatory cytokines, such as interleukin 6 (IL-6), has been described as an early response, followed by an adaptive immune response with the production of antibodies. IL-6 is produced in response to viral infections and is crucial for the activation of T cells and the differentiation of B cells, which produce antibodies. Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are produced during the initial acute period of infection and the recovery period from the period of onset of symptoms. There has been some relationship between the innate response of the cytokine and the adaptive response of the antibodies in patients with COVID-19 infection. There has been a positive correlation between IL-6 levels and the presence of COVID-19 antibodies, suggesting that higher IL-6 levels may be associated with a stronger immune response and studies have confirmed that patients with higher IL-6 levels have a higher antibody response. High IL-6 levels on admission observed within 2 weeks after onset of symptoms were positively correlated with high concentrations of IgG seen 5 weeks after onset of symptoms. We have previously described elevated IL-6 levels in the sera of 68% of COVID-19 convalescent patients (40–93 days) post-onset of symptoms (recovery phase). In this study we decided to investigate whether there was some relationship between the IL-6 levels in patients 40–93 days post-onset of symptom in the recovery phase and their antibody response using a wide range of antibody assays (iCHROMA IgG, GOLD IgG &amp; IgM, Abbott SARS-CoV-2 IgG II Quant-test (Abbott S IgG), Diasorin Liaison SARS-CoV-2 S1/2 (Diasorin S1/2 IgG). The patients were divided into two groups, those with normal IL-6 levels (&lt;7 pg/ml) and those with elevated IL-6 levels (&gt;7 pg/ml). All patients (100%) had positive IgG antibodies, only 8 out the 28 patients (29%) were positive for IgM antibodies. The mean antibodies concentrations of the patients (n = 9) with normal IL-6 levels (&lt;7 pg/ml) for iCHROMA IgG (20.0 Units), GOLD IgG (34.4 AU/mL), Abbott IgG (4175 AU/mL), Diasorin Liaison IgG (75.8 AU/mL) and GOLD IgM (4.7 AU/mL), respectively. The mean antibodies concentrations of the patients (n = 19) with elevated IL-6 levels (&gt;7 pg/ml) for iCHROMA IgG (20.9 Units), GOLD IgG, (34.9 AU/mL), Abbott IgG (2287 AU/mL), Diasorin Liaison IgG (121.7 AU/mL) and GOLD IgM (11.2 AU/mL), respectively. The antibodies of the patients with the elevated IL-6 levels were significantly higher for Diasorin Liaison IgG (p = 0.02) and GOLD IgM (p = 0.003) but lower for Abbott IgG (p = 0.02). In conclusion, this study using a panel of antibody assays highlights that increased levels of IL-6 in the convalescent phase (recovery phase) indicate an active immune response leading to higher concentrations of antibodies especially IgM, suggesting that cytokine storms and re-infection occur in the recovery phase.

Prevalence of COVID-19 antibodies in employees of St. Jacob Hospital in Bardejov.

The COVID-19 disease caused by the SARS-CoV-2 virus belongs to the group of highly infectious diseases with increased mortality and morbidity in the population. Finding the presence of antibodies plays an important role while finding the number of individuals who overcame the disease or were vaccinated. A total of 250 employees of St. Jacob Hospital with Polyclinic, Bardejov, participated in our study, the blood samples were drawn from the index finger and processed with the help of the rapid Ag test for the detection of antibodies and venous blood using the ELISA method. The health workers (doctors, nurses, medical laboratory technicians, laboratory diagnosticians) tested during September and October 2022 participated in our study. Our experimental study shows the presence of IgG antibodies in 215 (86%) of employees, who get them from overcoming the COVID-19 disease or getting vaccinated. In 17 (6.8%) of employees were detected IgG and IgM antibodies. The biggest number of IgG antibodies was found in 36 (78%) employees of the Surgical Department, 28 (84%) employees of Rehabilitation Department and 25 (89%) employees of the Internal Department, when compared with the Department of Laboratory Medicine 9 (30%) employees and Radiology Department 4 (44%) employees. Multiple prevalence of COVID-19 disease were found in employees of the internal, surgical and rehabilitation departments in whom we detected a higher presence of IgG antibodies. In department of laboratory medicine workers were proven lower levels of IgG antibodies, mainly for the limited contact with the positive covid patients and working with only their biological material, compared to the first-line employees exposed to direct contact with the patients.

Differences Of COVID-19 Antibody Titer In The Group After The Two Sinovac Vaccine And The Three Moderna Of Prodia Employees Yogyakarta

This study compared antibody levels in individuals after receiving the second dose of the Sinovac vaccine and the third dose of the Moderna vaccine. Sinovac, developed in China, uses the inactivated virus method, meaning it contains no live virus. In contrast, the Moderna vaccine, created in the United States, is an mRNA vaccine that prompts the immune system to produce spike proteins, leading to antibody production without using a live virus. Conducted on Prodia employees in Yogyakarta, this observational research used a cross-sectional approach to measure antibody titers after vaccination. The results, analyzed using the Wilcoxon signed test, showed a significant difference in COVID-19 antibody levels between the two groups.

Faradaic Impedimetric Immunosensor for Label-Free Point-of-Care Detection of COVID-19 Antibodies Using Gold-Interdigitated Electrode Array.

Label-free electrochemical biosensors have many desirable characteristics in terms of miniaturization, scalability, digitization, and other attributes associated with point-of-care (POC) applications. In the era of COVID-19 and pandemic preparedness, further development of such biosensors will be immensely beneficial for rapid testing and disease management. Label-free electrochemical biosensors often employ [Fe(CN)6]-3/4 redox probes to detect low-concentration target analytes as they dramatically enhance sensitivity. However, such Faradaic-based sensors are reported to experience baseline signal drift, which compromises the performance of these devices. Here, we describe the use of a mecaptohexanoic (MHA) self-assembled monolayer (SAM) modified Au-interdigitated electrode arrays (IDA) to investigate the origin of the baseline signal drift, developed a protocol to resolve the issue, and presented insights into the underlying mechanism on the working of label-free electrochemical biosensors. Using this protocol, we demonstrate the application of MHA SAM-modified Au-IDA for POC analysis of human serum samples. We describe the use of a label-free electrochemical biosensor based on covalently conjugated SARS-CoV-2 spike protein for POC detection of COVID-19 antibodies. The test requires a short incubation time (10 min), and has a sensitivity of 35.4/decade (35.4%/10 ng mL-1) and LOD of 21 ng/mL. Negligible cross reactivity to seasonal human coronavirus or other endogenous antibodies was observed. Our studies also show that Faradaic biosensors are ~17 times more sensitive than non-Faradaic biosensors. We believe the work presented here contributes to the fundamental understanding of the underlying mechanisms of baseline signal drift and will be applicable to future development of electrochemical biosensors for POC applications.

Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents

ABSTRACT Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

Case 324.

A 69-year-old right-handed man with a history of substance use disorder, hypertension, and diabetes presented to the emergency department in an unresponsive state. Upon examination, apart from tachycardia (heart rate, 108 beats per minute), vital signs were within normal ranges (blood pressure, 134/102 mm Hg; temperature, 97.9°F [36.6°C]; respiratory rate, 16 breaths per minute; oxygen saturation, 96%). He had a Glasgow coma scale score of 8. Otherwise, the physical examination revealed no abnormalities. His prior psychiatric and surgical histories were unremarkable. There was no history of recent travel, camping, hiking, or vaccination. No family history could be obtained. Laboratory work-up revealed an elevated creatine kinase level (49 006 U/L [818.4 μkat/L]; normal reference range, 10-205 U/L [0.17-3.42 μkat/L]). An electrocardiogram showed sinus tachycardia without evidence of cardiac ischemia. An echocardiogram was unremarkable. Alanine aminotransferase (126 U/L [2.10 μkat/L]; normal reference range, 0-40 U/L [0-0.67 μkat/L]) and aspartate aminotransferase (488 U/L [8.15 μkat/L]; normal reference range, 3-44 U/L [0.05-0.74 μkat/L]) levels were elevated. Polymerase chain reaction results were negative for HIV-1, HIV-2, syphilis treponemal, and COVID-19 antibodies. The rest of the routine laboratory work-up findings were within normal limits. Urine drug screening was positive for cocaine, marijuana, fentanyl, and benzodiazepines. Naloxone was administered, but the patient remained unresponsive. Intubation was performed for airway protection. Noncontrast and contrast-enhanced CT of the head (Fig 1) and CT angiography were performed in the emergency department to rule out an acute intracranial abnormality. Multisequence MRI of the brain with administration of intravenous contrast material was ordered for further assessment (Figs 2-4). CT of the abdomen and pelvis was unremarkable (images not shown).

527. A Descriptive, Retrospective Analysis of COVID-19 Antibody Therapy and its Effects on Morbidity and Mortality in Patients Receiving B-cell Depleting Therapies

Abstract Background Patients receiving B-cell-depleting therapies (BCDT) are at an increased risk for severe COVID-19. Passive antibody therapy (PAT), including COVID-19 convalescent plasma (CCP) and monoclonal antibodies (MAB), is hypothesized to be an effective treatment in this population. However, real-world data on their effectiveness is limited. Methods We conducted a retrospective chart review of patients who contracted COVID-19 within a year from their last BCDT treatment and later received PAT (Table 1). Response to treatment was assessed by 90-day COVID-related mortality and all-cause morbidity, defined through number of hospitalizations (Figure 1).Table 1.Inclusion and exclusion criteria.Figure 1.Patient flow. Sixty-five patients met initial criteria. Five were excluded from analysis due to non-COVID related death within 90 days from COVID diagnosis. Cause of death was established in the chart and confirmed by review of two investigators. Results From 60 included patients, the majority were Caucasians (97%), females (57%), and vaccinated (67%) (Table 2). Most patients received rituximab (53%) for treatment of a hematological malignancy (37%) or multiple sclerosis (37%) (Figure 2). Overall morbidity (3/39, 7.7%) and mortality (3/60, 5%) were low. All hospitalized and deceased patients were elderly Caucasian males receiving rituximab for underlying hematological malignancy. All deceased patients received inpatient treatment, 2 with CCP and one with MAB (Figure 3).Table 2.Basic characteristics of passive antibody therapy recipients. Demographics, vaccination status and number of comorbidities excluding the condition which is the indication for B-cell depleting therapy.Figure 2.Type of B-cell depleting therapy and indication for use.Evaluated B-cell depleting therapies are rituximab (n=32), ocrelizumab (n=21), obinutuzumab (n=6), ofatumumab (n=1). Evaluated underlying indications for B-cell depleting therapy are hematological malignancy (n=22), multiple sclerosis (n=22); rheumatoid arthritis (n=9) and others (n=7). Others include scleroderma (n=1), systemic lupus (n=2), granulomatosis with polyangiitis (n=4).Figure 3:Treatment location and type of passive antibody therapy.All patients treated outpatient (39) received monoclonal antibodies. Of inpatients (21), 14 received COVID-19 convalescent plasma. Of patients treated as outpatient, 3 were hospitalized, with only 1 hospitalized for a COVID-related illness. Conclusion COVID-19 patients undergoing BCDT and treated with PAT had low morbidity and mortality in our study, suggesting a possible benefit of PAT in this patient population. All deaths occurred in patients hospitalized at the time of treatment with PAT, implying advanced COVID-19 infection and highlighting the importance of early PAT administration. All deceased patients and 2/3 hospitalized patients were receiving rituximab, suggesting that rituximab may be a risk factor for severe COVID (Figure 4). All deceased and hospitalized patients had an underlying hematological malignancy, suggesting that the presence of hematologic malignancy may impact the outcome of COVID-19. In our study, elderly Caucasian males with multiple medical comorbidities and underlying hematological malignancy treated with BCDT, particularly rituximab, may have an increased risk for severe COVID-19. Early PAT administration may improve outcomes in this group of patients, and they should be prioritized for treatment when access to PAT is limited.Figure 4:Type of B-cell depleting therapy and mortality. All deaths were among patients being treated with rituximab for hematological malignancy. Disclosures All Authors: No reported disclosures

546. COVID-19 Monoclonal Antibody Use at a Stand Alone Children’s Hospital

Abstract Background Texas Children’s Hospital (TCH) implemented an outpatient clinic for eligible patients to receive infusions when COVID monoclonal antibodies (mAbs) were approved for use in non-hospitalized, high-risk patients with mild to moderate COVID-19. There are limited data evaluating the use of outpatient COVID mAbs in pediatric patients. We describe the clinical characteristics and outcomes of the patients treated with COVID mAbs at TCH. Methods Patients that were referred to receive COVID mAbs from 12/1/2020 to 5/5/2022 were included. Information collected included demographics, comorbidities, refusal reason, adverse events, emergency center (EC) visits or admission within 14 days after final dose, and EC visit or admission within 14 days of referral if patients did not receive COVID mAbs. Chi-square was used to determine differences between the groups. Results There were 262 patients referred during the study period. The median age of all referred patients was 15.8 years (IQR 14-17.4 years). Majority of referrals were for treatment of COVID-19 infection rather than post-exposure prophylaxis (92.8% vs 7.2%). Of the 262 referrals, 134 patients received COVID mAbs (51.2%) while 128 patients were not treated. Majority of the patients received casirivimab-imdevimab (73.9%). The comorbidities of all patients are shown in Figure 1. The most common reasons for patients to not receive COVID mAbs were no drug available or not listed, and the full list of reasons are listed in Figure 2. The median time from reported symptom onset to infusion was 4 days (IQR 2-6 days). Of the 134 infused patients, 8 patients (6%) visited the EC within 14 days from infusion, and 6 (4.5%) were admitted while 4 patients (3.1%) that did not receive an antibody visited the EC resulting in 3 admissions (2.3%) (EC visits p=0.27; admissions p=0.34). There were 11 patients (8.2%) that experienced adverse events from their infusion, which led to 5 of the 8 EC visits. Comorbidities were similar across the infused and non-infused groups (p=0.16). Number of high-risk conditions represented by all referred, high-risk patients Number of patients for each reason for not receiving a COVID-19 antibody infusion Conclusion COVID mAb treatments were well tolerated among pediatric patients. Majority of patients in both groups did not require EC visit or hospitalization. More data are needed to determine the clinical efficacy of mAbs patients. Disclosures Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB Lisa Forbes Satter, MD, ADMA: Advisor/Consultant|CsL Behring: Advisor/Consultant|Grifols: Advisor/Consultant|incyte: Advisor/Consultant|Pharming: Advisor/Consultant|Takeda: Advisor/Consultant

The Influence of Comorbidities, General Health Status, and Self-Care Self-Efficacy on COVID-19 Symptoms During the Omicron Wave.

Background The emergence of the less virulent COVID-19 strains such as Omicron and its subvariants shifted the paradigm of COVID-19 treatment from inpatient treatment to regular outpatient care. The individual health determinants affecting COVID-19 disease severity among vulnerable adults treated in outpatient settings are an under-researched area. Methods This study conducted in an outpatient COVID-19 antibody infusion center employed a cross-sectional survey design to explore the impact of comorbidities, general health status, and self-care self-efficacy on COVID-19 symptom severity. We recruited 120 COVID-19-positive participants over 40 years of age, of which 117 completed the study with 87 providing complete data. After the screening and consenting process, the participants completed the following surveys in a secure REDCap survey software (Vanderbilt University, Nashville, USA)on an iPad (Apple Inc., Cupertino, USA): 1) sociodemographic questionnaire, 2) Charlson Comorbidity Index (CCI) to capture comorbidities, 3)Medical Outcomes Study Short-Form (SF-12) to assess general health including physical (PCS) and mental (MCS) health subscales, 4) Self-Care Self-Efficacy Scale (SCSES) to measure self-care self-efficacy, and 5) the COVID-19 Symptom rating scale (COVID-19 SRS). Statistical analysis used were Chi-square and Pearson correlations. Results As evidenced by CCI, the top five comorbidities were hypertension (42%), diabetes mellitus (31%), pulmonary disease (19%), depression (14%), and solid tumors (11%). Age was statistically significantly correlated to comorbidity burden(p<0.0001). Severe COVID-19 symptoms reported were fatigue, myalgia, cough, runny nose, and sore throat. The general health status measure (SF-12) subscales showed that the patient's mental component summary (MCS) was more statistically significant to COVID-19 symptom severity than the physical component summary (PCS). The MCS demonstrated a statistically significant correlation with fatigue and myalgia (p<0.0001), headache and breathing difficulties (p<0.001), nausea/vomiting (p<0.01), and abdominal pain/diarrhea (p<0.05). The PCS showed a lesser statistically significant correlation with fatigue, myalgia, headaches (p<0.01), fever/chills, cough, congestion/runny nose, night sweats, breathing difficulties, nausea/vomiting, and abdominal pain/diarrhea (p<0.05). Interestingly, the 'loss of smell' which is the hallmark symptom of COVID-19 was the only symptom that showed a statically significant correlation with the Charlson Comorbidity Index (p<0.05), and it did not show any association with either mental (SF-12 MCS) or physical (SF-12 PCS) health status. The SF-12 MCS also showed a statistically significant correlation with a diagnosis of depression (p< 0.01), validating it as a true measure of mental health among vulnerable adults. The SCSES was not correlated with any of the COVID-19 symptoms. Conclusions The patient's general health status, especially mental health was more statistically significant to COVID-19 symptoms. The COVID-19 hallmark symptom of 'loss of smell' was the only symptom that showed statistical significance with comorbidities. Within the limitations of a cross-sectional survey design and convenient sampling methods, this study calls to tailor general health status, especially mental health, and cumulative comorbidity burden to risk assessment/risk stratification of COVID-19 care.