Asymptomatic COVID-19 Infection Research Articles

Single SARS virus mutation as a possible cause of the prevalence of asymptomatic COVID-19 infection forms

To explain the prevalence of asymptomatic SARS-CoV-2 infection forms, a hypothesis on a single virus mutation that causes changes in two important factors such as virus infectiousness and pathogenicity is proposed. According to this hypothesis, susceptible and asymptomatic forms affect the rate of change in infectiousness and pathogenicity, thereby influencing the rate of infectivity and the onset of a disease and as a result, altering the ratio of asymptomatic forms to symptomatic cases. With a mathematical model, constructed based on this hypothesis and identified using data from the first wave of COVID-19 in Saint-Petersburg, a correlation between changes in microbiological parameters of the model and changes in a ratio of asymptomatic forms to symptomatic cases is verified. It is concluded that single virus mutation may affect the ratio.

Single SARS Virus Mutation as a Possible Cause of the Predominance of Asymptomatic COVID-19 Infection Forms

Single SARS Virus Mutation as a Possible Cause of the Predominance of Asymptomatic COVID-19 Infection Forms

The effect of Psidium guajava Leaves’ extract for mild and asymptomatic corona virus Disease-19

COVID-19 is an emerging disease that attacks the respiratory and systemic systems. Various treatments have been used for COVID-19, but no antiviral agents seemed to be efficacious. Many medicinal plants are commonly used for viral infections in Indonesia, including the guajava leaf. The study aimed to determine the effects of Psidium guajava extract supplementation on inflammation markers of asymptomatic and mild COVID-19 patients. The conversion time of PCR results was also evaluated. This study was an experimental, single-blinded, randomized clinical trial (ClinicalTrials.gov: NCT04810728) comparing the efficacy of P. guajava extract at the dose of 1000 mg/8h on top of standard treatment with the standard treatment only for asymptomatic and mild COVID-19 subjects. The primary endpoints were neutrophil and lymphocyte percentages as well as the neutrophil/lymphocyte ratio (NLR) on day 7 of the treatment. The secondary endpoints were high-sensitivity c-reactive protein (hs-CRP) level, PCR-based conversion time, and recovery rate at weeks 2 and 4. A total of 90 subjects were enrolled, and there were 40 subjects in the P. guajava (experimental) group and 41 subjects in the control group who completed the research. On day 7, significantly lower percentage of neutrophil (52.4% vs 58.9%, p = 0.002), higher lymphocyte percentage (35.5%, vs 29.7%, p = 0.002), and lower NLR (1.5 vs 2.1, p = 0.001) were demonstrated in the experimental versus control group. The PCR-based conversion time was shorter (14 days vs 16 days, p < 0.001), and recovery rate at 2 and 4 weeks were higher (49% vs 27%, p = 0.03 and 100% vs 82%, p = 0.003, respectively) in the experimental group. There were no differences in the baseline characteristics. P. guajava extract supplementation reduced neutrophil and increased lymphocyte percentages which led to reduced NLR, accelerated PCR-based conversion time, and increased recovery rate in subjects with mild and asymptomatic COVID-19 infection.\\

SARS-CoV-2 infection characteristics among students and staff in a large high school COVID-19 outbreak and secondary transmission in households

BackgroundSARS-CoV-2 clinical presentation is associated with the patients’ age group. Overall, young individuals present higher proportions of asymptomatic or mild COVID-19 infection, compared to adults. Data on secondary COVID-19 transmission in households, according to the cases’ age group, are accumulating. MethodsWe performed a follow-up cohort study including all COVID-19 real-time polymerase chain reaction (RT-PCR)-confirmed cases (adolescent students and school staff) diagnosed in an epidemiological investigation of a large high school outbreak. We compared the adolescent and adult groups regarding clinical symptoms, time to negative COVID-19 RT-PCR tests, and infection transmission in households. ResultsThe study population included 817 persons. The confirmed COVID-19 RT-PCR outbreak cases (n = 178) were followed (students aged 12–19 years, median age 14 years, n = 153, school staff aged 24–67 years, median age 39 years, n = 25) and the cases’ household close contacts (n = 639) were tested. The adolescents had lower symptomatic infection rates, shorter time to negative COVID-19 RT-PCR tests, and lower transmission rates to household members, compared to the adults. The general transmission rate among household contacts was 13.5%, (86/639) ranging from 8.6% in asymptomatic students’ contacts to 27.3% in symptomatic staff contacts. COVID-19 transmission rates were significantly higher in contacts of symptomatic cases compared to asymptomatic cases (odds ratio: 2.06, 95% CI 1.26–3.4) and higher in adults compared to adolescents (odds ratio: 2.69, 95% CI 1.43–4.89). ConclusionsAdolescents and adults diagnosed in an outbreak investigation differ as to COVID-19 clinical presentation and transmission. As adolescents may show mild or no symptoms, COVID-19 prevention in school settings is challenging. Implementing nonpharmaceutical measures and promoting vaccination programs in eligible staff and students should be considered.

Potent SARS-CoV2-specific T-cell response in asymptomatic hemodialysis patients with hidden COVID-19 infection history.

COVID-19-related immune responses in patients with end-stage renal disease (ESRD) are characterized in detail by the humoral response, but their cellular immunity has not been clarified. Here, we evaluated virus-specific T cells in parallel with serology-related tests. In this study, 104 ESRD patients at the hemodialysis ward of Imam Reza hospital at Tabriz (Iran) were enrolled. After blood sampling, SARS-CoV2-specific humoral and cellular immune responses were evaluated by SARS-CoV2-specific IgM/IgG ELISA and peptide/MHCI-Tetramers flow cytometry, respectively. Our results showed that 14 (13.5%) and 45 (43.3%) patients had specific SARS-CoV2 IgM and IgG in their sera, respectively. Immunophenotyping for SARS-CoV2-specific CD8+ T lymphocytes revealed that 68 (65.4%) patients had these types of cells. Among SARS-CoV2-specific CD8+ T lymphocytes positive subjects, 13 and 43 individuals had positive results for specific SARS-CoV2 IgM and IgG existence, respectively. Also, there was a relationship between specific SARS-CoV2 IgM (p=0.031) and IgG (p < 0.0001) existence and having SARS-CoV2-specific TCD8+ lymphocytes in the studied population. Despite not having clinical symptoms, a high rate of SARS-CoV2-specific T-cell response in asymptomatic ESRD patients may reveal a high burden of asymptomatic COVID-19 infection in these patients.

Real-time transcription polymerase chain reaction cycle threshold values as criteria for utilization of incidental COVID-19 positive lung donors.

Shortage of organ donors is an ongoing limiting factor in lung transplantation (LT). Despite increasing prevalence of asymptomatic COVID-19 infection, positive COVID-19 testing from a potential donor remains a contraindication at many LT centers. In this report, we present the outcomes of LT utilizing an algorithm based on donor clinical presentation, and COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) with cycle threshold (Ct) values evaluation. The Ct value threshold for organ acceptance was >35. A total of 8 COVID-positive donors were included. No donor-to-recipient transmissions of COVID-19 were observed. Short-term outcomes were comparable to those reported in pre-COVID literature. Survival-to-date is 100% with median POD of 161 days. Our findings support the safety and efficacy of utilizing our algorithm including Ct value threshold for selection of donors with incidental COVID-19 positive testing.

Filter Questions in Symptom Assessment Affect the Prevalence of (A)Symptomatic COVID-19 Cases.

It has been reported that a substantial number of COVID-19 infections are asymptomatic, with both symptomatic and asymptomatic infections contributing to transmission dynamics. Yet, the share of asymptomatic cases varies greatly across studies. One reason for this could be the measurement of symptoms in medical studies and surveys. In 2 experimental survey studies (total N > 3,000) with participants from Germany and the United Kingdom, respectively, we varied the inclusion of a filter question on whether participants who tested positive for COVID-19 had experienced symptoms prior to presenting a checklist of symptoms. We measured the reporting of asymptomatic (versus symptomatic) COVID-19 infections. The inclusion of a filter question increased the reporting of asymptomatic (versus symptomatic) COVID-19 infections. Particularly mild symptoms were underreported when using a filter question. Filter questions affect the reporting of (a)symptomatic COVID-19 cases. To account for such differences in the estimation of population infection rates, future studies should transparently report the applied question format. Both symptomatic and asymptomatic infections are important for COVID-19 transmission dynamics.In previous research, symptoms have been assessed either with or without a filter question prior to presenting a symptom list.We show that filter questions reduce the reporting of asymptomatic infections.Particularly mild symptoms are underreported when using a filter question.

Antibody response to ChAdOx1 nCoV-19 (Covishield®) vaccine in people on maintenance hemodialysis.

People on renal replacement therapy (RRT) have a high risk ofCOVID-19 infection and subsequent death. COVID-19vaccination is strongly recommended for thoseonRRT. Dataare limited on the immune response of the ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine in patientsonRRT. A prospective cohort of adult (age > 18 years),onRRTintheformof hemodialysis were included and received two intramuscular doses of Covishield®. A blood specimen of 5.0mL was collected at two time points, within a few days before administering the first dose of the vaccine and at 4-16 weeks after the second dose. According to their prior COVID-19 infection status, the participants were grouped as (i) prior symptomatic COVID-19 infection, (ii) prior asymptomatic COVID-19 infection, and (iii) no prior COVID-19 infection. A large proportion (81%) of participants had anti-spike antibodies (ASAb) before vaccination, and a reasonable proportion (30%) also had neutralizing antibodies (NAb). The titer of ASAb was relatively low (207 U/mL) before vaccination. The ASAb titer (9405 [1635-25,000] U/mL) and percentage of NAb (96.4% [59.6-98.1%]) were markedly increased following the administration of two doses of the vaccine. The participants' prior COVID-19 exposure status did not influence the rise in ASAb titer and NAb percentage. Further, administering two doses of the Covishield vaccine helps them achieve a high ASAb titer. Two doses of ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine, given 12 weeks apart, achieve a high titer of ASAb and a high percentage of NAb in people on hemodialysis.

Proactive use of QI methodology in consultation-liaison psychiatry to support the opening of a new COVID+ behavioral health inpatient unit during the omicron surge

Inpatient consultation-liaison (CL) psychiatry teams routinely facilitate the transfer of medically stable patients in behavioral health crisis from the general hospital to inpatient psychiatric units. The COVID-19 pandemic had a significant impact on this process when inpatient psychiatric units were unable to provide care for patients with asymptomatic COVID-19 infection because of infection control concerns in units unable to accommodate isolation precautions. Similar to other disrupted hospital workflows, these clinical handoffs became more complicated by requiring COVID exposed or COVID+ patients in the midst of behavioral health crisis to quarantine or isolate on general hospital units if not otherwise stable for discharge to the community. To better respond to the growing number of patients isolating in the general hospital during the 2022 Omicron surge, we used quality improvement (QI) methodology to illustrate the need to create a COVID+ unit in the inpatient psychiatric hospital to care for the growing cohort of COVID+ patients in psychiatric crisis who were otherwise unable to access traditional psychiatric hospital care because of their isolation status.

Postoperative outcomes in patients undergoing elective general surgery after recovery from Covid-19 at a tertiary care centre: A one-year case series.

Background Planned elective surgery had to be postponed for a large number of patients who tested positive for Covid-19 in the preoperative period. We aimed to assess the postoperative outcomes of patients who were operated on for elective indications, following recovery from Covid-19 infection. Methods We did a retrospective study of patients who underwent elective general surgery between 1 April 2020 and 31 March 2021, following recovery from Covid-19. The 30-day postoperative morbidity and mortality were analysed. The data relevant for the study were retrieved from the hospital's electronic medical records. Results Of the 109 patients included, 54.1% were women and the median (range) age was 49 (16-76) years; 53.2% of operations were performed for benign indications and the rest were for malignancies. Eighty-five (78%) patients underwent surgery following recovery from an asymptomatic Covid-19 infection and 23 (21.1%) patients following recovery from mild Covid-19 infection; 73.3% of the operations were performed following a planned delay of 2- 5 weeks from the diagnosis of Covid-19. The 30-day major postoperative morbidity (Clavien-Dindo grade ≥3) was 6.4%, the postoperative pulmonary morbidity was 0.9%, and there was no 30-day mortality. Conclusions Elective general surgical procedures can be done safely in patients who have recovered from asymptomatic and mild Covid-19 infection, following a minimum wait period of 2 weeks.

Impact of Covid-19 pandemic on upper gastrointestinal cancer services: Experience from an oncosurgical unit.

Background The Covid-19 pandemic continues to affect the delivery of cancer care across the world. We evaluated the impact of the pandemic on the delivery of cancer care, to patients diagnosed with upper gastrointestinal (UGI) tract malignancies, during the first 4 months of the pandemic in India. Methods We retrospectively analysed a database of patients with UGI malignancies discussed in the Multidisciplinary Tumour Board (MDTB) between 24 March and 24 July 2020. The results in the study group were compared to that of a similar group of patients from the corresponding period in 2019. Results A total of 117 and 61 patients were discussed in the MDTB in 2019 and 2020, respectively, thereby showing a 48% reduction in the number of new cases seen in 2020. The reduction in the number of new cases was huge for oesophageal cancer (53-13; 75.5% reduction), compared to gastric cancer (53-43; 18.9%). The proportion of patients with metastatic disease at presentation was significantly higher in 2020, compared to 2019 (39.3% v. 23.1%; p=0.023). In 8 (13.1%) patients, the pre-existing treatment protocol had to be modified to suit the prevailing pandemic situation. Two patients with gastric cancer acquired asymptomatic Covid-19 infection during the treatment, which delayed the delivery of further therapy. Oncosurgeries were less in 2020 compared to 2019 (25 v. 63). The rate of 30-day major postoperative complications in 2020 was comparable with that in 2019 (12% v. 6.3%; p=0.4). Conclusions The number of new patients with UGI cancer, seeking elective cancer care and the number of oncosurgical procedures reduced during the Covid-19 pandemic. Continuous delivery of UGI cancer services was ensured during the pandemic through clinical prioritization, the adaptation of specific care pathways and selective modification of protocols, to suit the prevailing local conditions.

Asemptomatik COVID-19 ve Pulmoner Emboli İlişkisi: Olgu-Kontrol Çalışması

Objective: The incidence of pulmonary embolism (PE) has increased in coronavirus disease-2019 (COVID-19) infection. The aim of study is to determine whether there is an increase in the frequency of PE in asymptomatic COVID-19 patients. Material and Methods: Patients who were diagnosed with PE our hospital, who did not have COVID-19 and who were not vaccinated against COVID-19 were included in the study group and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody levels were examined. The control group was consisted of patients who did not have PE, had not had COVID-19 and were not vaccinated and SARSCoV-2 antibody levels were examined. The antibody positivity rates, antibody titer levels of both groups were compared. Results: A total of 32 patients, 16 in the study group and 16 in the control group, were included in the study. Of all patients, 22 (68.8%) were male, 10 (31.3%) were female. While the mean age of men was 47.36±14.86, women was 51±24.463 (p=0.671). There was no statistically difference between the 2 groups in terms of mean age (p=0.346). When the groups were compared in terms of SARS-CoV-2 antibody, antibody positivity was found in 7 (43.8%) patients in both the study group and the control group (p=1.000). There wasn't difference between the groups antibody titers (p=0.275). The rate of asymptomatic COVID19 infection in patients with PE was found to be similar to the population followed with non-PE diagnoses. Conclusion: The results of study show that there is no increase in the risk of PE in patients with asymptomatic COVID-19 infection.

Impact of asymptomatic and mild COVID-19 infection on fetal growth during pregnancy

BackgroundDuring pregnancy, certain viral infections are known to significantly affect fetal development. Data regarding the impact of COVID-19 viral infection in pregnancy, specifically in asymptomatic or mild cases, remains limited. This presents a challenge in providing prenatal counseling and antepartum surveillance in pregnancies complicated by COVID-19 infection. Placenta studies have demonstrated that vascular malperfusion patterns attributed to COVID-19 appear to depend on the timing of infection. Given these placental changes, we aim to evaluate the impact of COVID-19 on fetal growth in pregnant patients with asymptomatic or mild disease, stratified by trimester of infection. We hypothesize that COVID-19 infection, especially early in pregnancy, increases the risk of fetal growth restriction (FGR).Study design.This is a single institution, retrospective cohort study of patients ages 16–55 years old with a singleton delivery between December 10, 2020, and April 19, 2021 who had not received a COVID-19 vaccination prior to delivery. COVID-19 infection during pregnancy was defined as a positive SARS-CoV-2 RT-PCR test. FGR was defined as an estimated fetal weight less than the 10th percentile for gestational age or abdominal circumference less than the 10th percentile for gestational age. Maternal and fetal characteristics, including FGR, were compared between women with versus without COVID-19 infection during pregnancy. ResultsAmong 1971 women with a singleton delivery, 208 (10.6 %) had a prior asymptomatic or mild COVID-19 infection during pregnancy. With the exception in the median prenatal BMI being significantly higher in the COVID-19 group (median, 27.5 vs 26.3, p = 0.04), there were no significant differences in demographics, baseline maternal comorbidities or gestational age between those with versus without COVID-19 infection during pregnancy, or in the proportion of their offspring with FGR (3.4 % (7/208) vs 4.8 % (84/1763), p = 0.36). When the 208 women were stratified by the timing of their COVID-19 infection, the proportion with an offspring with FGR was 8.7 % (2/23), 1.2 % (1/84), and 4.0 % (4/101), for those first diagnosed with COVID-19 during the 1st, 2nd, and 3rd trimesters, respectively (p = 0.72 Cochran-Armitage test for trend). ConclusionAsymptomatic or mild COVID-19 infection in pregnancy, regardless of timing of infection, does not appear to be associated with FGR. Routine serial fetal growth assessment may not be warranted solely for history of COVID-19 infection.

Efficacy of Anti-Sars-Cov-2 mRNA Vaccines in Adults with Severe Acquired Aplastic Anemia with or without Allograft

Introduction: Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against COVID-19 infections, especially in immunocompromised hosts. Several studies have now demonstrated a good response to SARS-CoV-2 mRNA vaccines in allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients. In the specific context of acquired severe aplastic anemia (ASAA), some data exist on post-vaccination results after treatment by horse antithymocyte globulin (hATG) and cyclosporin (CsA) while a few cases of SAA have been related to COVID-19 infection. However, as yet, no specific results are available for ASAA patients (pts) who received an Allo-HSCT. Methods: This real life monocentric observational study aimed at describing the incidence and severity of COVID 19 infections and humoral responses after anti- SARS-Cov-2 mRNA vaccines in a cohort of 27 ASAA pts who received either an allo-HSCT (n=13) or hATG+CsA (n=14) between 2012 and 2022 in our Hematology Department. Data were collected in personal file records, during routine follow-up visits or using phone contact. COVID 19 infection severity was defined by the need for hospitalization and/or subsequent related death. Antibody responses to the SARS-CoV-2 spike protein receptor-binding domain were also considered (all tests using Elecsys®, Roche, Rotkreuz, Switzerland), the highest value being >2500 BAU/mL. Based on a threshold of 250 BAU/mL, responses were classified as "weak" or "good, higher levels having been shown to correlate with the rate of neutralizing antibodies. Results: Pts characteristics are given in Table 1. None of the pts had presented a symptomatic or asymptomatic COVID-19 infection before V1. Afterwards, almost half of the pts (n=13, 48%) were documented with COVID 19 infection, mostly as a non-severe form (n=12, 92%, asymptomatic n=3 and mild n=9). Only one severe COVID 19 infection occurred and required hospitalization in intensive care unit for one month. This severe form occurred in the only pt who had not been vaccinated. This pt had been treated with hATG+CsA 18 months earlier and was still receiving CsA. The incidence of infection was similar between allo-HSCT (8/13) and ATG+CsA (5/14) pts (p=0.26), as well as in pts with idiopathic ASAA (8/12) or paroxysmal nocturnal hemoglobinuria (5/15; p=0.13). No difference either was seen between pts still under immunosuppressive therapy (CsA; 3/8) or not (10/19; p=0.76) or between pts vaccinated before (5/6) or after (8/20) Allo/hATG+CsA (p=0.16). All 3 patients who received only V1 and V2 vaccines contracted the infection and the incidence of COVID-19 infection was significantly lower in patients with 4 vaccines (11%) vs those with 3 (57%; p=0.05). After a median time of 36 days (range: 20 - 232) after V2, 75% (n=12/16) of the pts showed a good antibody response, 11 reaching the highest IgG titer, and this proportion increased after V3 and V4. Indeed, at a median time of 70 days (range: 17 - 221) after V3, 95% (n=19/20) showed a good antibody response, 17 pts reaching the highest IgG titer. At a median time of 60 days (range: 2-195) after V4, 100% (n=7/7) of the pts showed a good antibody response, 4 reaching the highest IgG titer. Conclusion: In this cohort, almost half of adults with ASAA presented with COVID-19 infection with no difference between patients previously allotransplanted and those who had received only hATG+CsA. Moreover, prolonged exposure to CsA did not appear to affect this incidence. Remarkably, none of the vaccinated patients presented a severe form of COVID-19 infection, indicating a very good efficiency of the vaccines. This protection increased with the number of shots as the incidence of COVID-19 was lower and the number of pts reaching good humoral response higher after a second booster. As the latter seems to be more protective, it should be proposed to all ASAA adult patients for whom systemic immune responses appear to be efficient. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Prospective Study Evaluating the Serological Profile of the Novel Coronavirus (COVID-19) Vaccines in Cancer Patients

Background: Immune-correlates of vaccine-induced immunity that can reliably predict the effectiveness of vaccines in real-world scenarios are desirable. The assessment of immunological measurements such as antibody levels have been used to detect chronic infections, previous infections and protective immunity against future infections including those derived from vaccines. We conducted a prospective study evaluating the antigenicity of COVID-19 vaccine and serological profile of cancer patients who received the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna COVID-19 vaccines. Methods: The study was approved by Ascension St. John Hospital IRB. We assessed four cohorts: Cohort A with active solid tumor malignancies on antineoplastic agents; Cohort B with active hematological malignancies on antineoplastic therapy; Cohort C with a history of cancer and Cohort D with no history of malignancy. Each subject required completion of the primary vaccination series of SARS-CoV2 vaccines with either BNT162b2 or mRNA-1273 without a previously documented or suspected SARS-CoV2 infection at the time of enrollment. Blood samples were collected for all the study patients for the analysis of serological profile between 3-8 months of the second dose of a SARS-CoV2 vaccine. The samples were batch processed to measure the levels of antibodies against SARS-CoV-2 spike (trimer) protein utilizing enzyme-linked immunosorbent assay (ELISA). Additionally, the levels of antibodies against SARS-CoV-2 spike (trimer), S1 subunit, S2 subunit, S1-receptor binding domain (RBD), and nucleocapsid were qualitatively assessed using SARS-CoV-2 Multi-Antigen Serology Module for Wes System (Protein Simple, CA). Data were analyzed using Student's t-test, analysis of variance, chi-squared analysis and the Mann-Whitney U test. Results: We enrolled 116 patients, with 37 in cohort A, 17 in cohort B, 13 in cohort C and 49 in cohort D. All cohorts were comparable with respect to mean age, mean BMI, sex and race. Table 1 shows mean antibody titers for all cohorts. Cohort B had the lowest antibody titer. Cohort A has the highest antibody titers including the nucleocapsid antibody titer which is suggestive of high rate of asymptomatic COVID-19 infection in this cohort. Antibody comparison data for cohorts A, C and D are presented in table 2. There was no statistically significant difference in antibody response between patients with solid tumor malignancy on antineoplastic agents as compared to patients without a history of cancer. A statistically significant difference in antibody response was only noted for the S1 subunit between cohorts A and C. Conclusions: Patients with active cancer on antineoplastic agents at the time of vaccination or with prior history of cancer not on antineoplastic treatment at the time of vaccination have equivalent antibody response when compared to patients without history of cancer. It is possible that patients with solid tumor malignancy on anticancer treatment have a higher rate of asymptomatic infection. Acknowledgements: This research is being supported by Sr. Verenice McQuade Endowment for Cancer Research. We thank our patients, research department, phlebotomists and clinical staff at Van Elslander Cancer Center for their assistance in conducting the study. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Concomitant Use of Sutimlimab and COVID-19 Vaccines in Patients with Cold Agglutinin Disease from the Phase 3 Cardinal and Cadenza Studies

Background: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia, characterized by chronic hemolysis mediated by classical complement pathway activation. The ongoing COVID-19 pandemic has posed an additional challenge in treating patients with CAD. Anti-CD20 therapies (commonly used off-label to treat CAD) increase the risk of serious COVID-19 infection and reduce the immune response to COVID-19 vaccines. Recent evidence has also shown a correlation between CAD exacerbations and both COVID-19 and COVID-19 vaccines; raising concern amongst clinicians as CAD patients are usually elderly with comorbidities and will likely require additional boosters during the ongoing pandemic. Sutimlimab (SUT), recently FDA approved for patients with CAD, is a first-in-class humanized monoclonal antibody which selectively targets C1s in the classical complement pathway; addressing the underlying mechanism of hemolysis in CAD. In the Phase 3 CARDINAL (NCT03347396) and CADENZA (NCT03347422) studies, SUT treatment led to rapid and sustained increases in hemoglobin and clinically meaningful improvements in fatigue and was generally well tolerated - reported adverse events (AE) were consistent with elderly populations. Both studies spanned the period before and during the pandemic; investigators were advised to vaccinate enrolled patients without stopping SUT treatment. However, the impact of SUT on immune response to COVID-19 vaccination is unknown. Objective: To explore concomitant use of COVID-19 vaccines and SUT in patients with CAD Methods: Post-hoc analysis from the open label extension (OLE) part of the CADENZA and CARDINAL studies. COVID-19 cases/diagnoses were collected via the regular AE reporting system. Data on tolerability to COVID-19 vaccine was collected through AE reports. Immunogenicity to COVID-19 vaccines was analyzed in a subset of patients fully vaccinated (2 doses) against COVID-19 and had consented to the use of stored samples (collected no later than 6 months after vaccination). Anti-Sars-CoV-2 Spike (EUROIMMUN Anti-SARS-CoV-2 ELISA) and anti-Sars-CoV-2 Nucleocapsid (Abbott Architect i2000 SR) IgG titers were measured. Three patients who tested positive for COVID-19 during Part A of both studies were excluded from the immunogenicity analysis. Results: Of the 61 completers from both studies, 47 received at least one dose of a COVID-19 vaccine; 14 received none; 11 had an additional booster. All participants, regardless of vaccination status, had similar demographic and clinical characteristics. Among those vaccinated, most (83%) received both doses during the studies; of these, mRNA vaccines were the most common (79%). The mean inter-dose interval for fully vaccinated patients (n=37) was 38 days; those who received 1 booster (n=11) had a mean of 165 days between the last dose and booster. No COVID-19 cases were reported during the OLE. Ten AEs were reported in 8 patients during the 7 days after any vaccine dose, but none more than once, and there were no serious AEs. SUT therapy was postponed/skipped twice due to vaccine administration, at the investigator's discretion. Anemia and hemolysis markers, including hemoglobin and total bilirubin, were measured after vaccination to assess its impact on hemolytic activity. No indications of hemolytic exacerbation were observed (Table 1). The immunogenicity analysis comprised 27 patients. All patients developed an immune response post-vaccination, measured via positive IgG anti-spike antibodies (Figure 1). The mean time between last dose and serum collection was 65 days (range: 25-137). Antibody titers were similar irrespective of gender or age. A further analysis performed on 6 patients with booster vaccinations demonstrated elevated immune responses pre to post booster (mean [95% CI] log10 titer change: 1.82 [0.79-2.85]). To rule out previous asymptomatic COVID-19 infection, anti-nucleocapsid SARS-Cov-2 IgG antibodies were assayed and were negative in all cases. Conclusions: COVID-19 vaccination response was not impaired in patients with CAD being treated with SUT. COVID-19 vaccines were well tolerated, and there were no signs of increased hemolytic marker activity following COVID-19 vaccination in patients receiving SUT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

BALANCING GVHD IMMUNOSUPPRESSION AND COVID19 VIRAL REACTIVATION IN A PATIENT WITH ATYPICAL COMPLETE DIGEORGE SYNDROME

<h3>Introduction</h3> Complete DiGeorge syndrome (DGS) accounts for less than 1% of patients with DGS, with atypical DGS being even rarer. We present a patient with atypical complete DGS who developed autoimmune phenomena attributed to autologous GVHD, and subsequent prolonged respiratory failure due to COVID19 pneumonia while on immunosuppression. <h3>Case Description</h3> A 3-year old male infant of a diabetic mother with complete DGS awaiting thymic transplantation, hypoparathyroidism, hypogammaglobulinemia on IVIG, and recent asymptomatic COVID19 infection was admitted for AKI, electrolyte disarray secondary to malabsorption, and warm autoimmune hemolytic anemia. A month prior he had a persistent eczematous rash, chronic cough, recurrent diarrhea, and thinning hair. Labs revealed uptrending total IgE to 10,000 IU/ml, no eosinophilia, an oligoclonal population of gamma-delta T cells, and increased numbers of CD4+ and CD8+ lymphocytes, which were primarily CD45RO+ central memory T cells. A large portion were activated and expressed HLA-DR. Mitogen proliferation was normal. Given these findings, he was diagnosed with autologous GVHD secondary to autoreactive oligoclonal T cells, and subsequently, atypical complete DGS. Tacrolimus and methylprednisolone were started for immunosuppression. IgE and CD3+ T cells decreased on immunosuppression, but he developed hypoxemic respiratory failure with prolonged intubation due to COVID19 pneumonia. Immunosuppression was gradually weaned. IgE and CD3+ cells increased slightly, but he showed no clinical signs of GVHD and was discharged home after a 3.5 month hospital stay. <h3>Discussion</h3> This case highlights the difficult balance between immunosuppression and viral reactivation. After starting immunosuppression for treatment of GVHD, he developed severe COVID19 pneumonia.

Prevalence of Asymptomatic COVID-19 Infection Among Air Medical Crew

<h3>Background</h3> Air medical transport of COVID-19 patients is challenging and presents a high-risk exposure for many air medical crew. Previous investigations have concluded that routine PPE utilized by air medical crew using routing personal protective equipment is safe and effective at preventing symptomatic COVID-19 infections. However, it is unclear to what extent providers may be exposed, contract COVID-19, and remain asymptomatic but potentially contagious. Previous reports suggest up to 6.4% of infected health care personnel are asymptomatic. <h3>Methods</h3> We conducted an IRB approved, primary mixed-methods research study that tested for COVID-19 antibodies in a cohort of participants previously surveyed regarding COVID-19 symptoms. Written consent was obtained by all participants. ELISA testing was performed at the University of New Mexico Center for Global Health Laboratory. Testing included measuring for COVID-19 antibodies in a manner that was independent of vaccination status. Participants also filled out a secure electronic survey to aide in the qualitative data collection and analysis. <h3>Results</h3> There were 42 participants. Labs samples were obtained between June 2021 and October 2021. Of the 42, 40 were vaccinated (95.2%) and 2 were unvaccinated (4.8%). Of the 40 who were vaccinated, 1 person had the 2-part Moderna vaccine, the rest had the 2-part Pfizer vaccine. 10 of 42 (23.8%) had experienced potential symptoms of COVID-19 at some point in time but had never had a positive test and 32 (76.2%) never experienced any symptoms. Of the 42, 4 had a positive ELISA test for COVID-19 antibody for a positivity rate of 9.52%. Out of the 4 subjects that tested positive, 3 (75%) never experienced any symptoms. <h3>Conclusion</h3> While the routine use of PPE has been proven to be effective in protecting air medical personnel from symptomatic COVID-19 infection, asymptomatic infection remains a concern. We found that 3 out of 4 that tested positive were asymptomatic. This is significant considering asymptomatic infection poses a risk to air medical crew, patients, coworkers, families, and the general public. Further investigation is required to better ascertain potential gaps in protective equipment or other latent sources of infection that pose risks to air medical crew.

Estimating the Effectiveness of Shielding during Pregnancy against SARS-CoV-2 in New York City during the First Year of the COVID-19 Pandemic.

Pregnant patients have increased morbidity and mortality in the setting of SARS-CoV-2 infection. The exposure of pregnant patients in New York City to SARS-CoV-2 is not well understood due to early lack of access to testing and the presence of asymptomatic COVID-19 infections. Before the availability of vaccinations, preventative (shielding) measures, including but not limited to wearing a mask and quarantining at home to limit contact, were recommended for pregnant patients. Using universal testing data from 2196 patients who gave birth from April through December 2020 from one institution in New York City, and in comparison, with infection data of the general population in New York City, we estimated the exposure and real-world effectiveness of shielding in pregnant patients. Our Bayesian model shows that patients already pregnant at the onset of the pandemic had a 50% decrease in exposure compared to those who became pregnant after the onset of the pandemic and to the general population.

Abnormalities in cardiac and inflammatory biomarkers in ambulatory subjects after COVID-19 infection.

BackgroundCoronavirus-2019 (COVID-19) is known to affect the heart and is associated with a pro-inflammatory state. Most studies to date have focused on clinically sick subjects. Here, we report cardiac and proinflammatory biomarkers levels in ambulatory young adults with asymptomatic or mild COVID-19 infection compared to those without infection 4–8 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) testing.Methods131 asymptomatic or mildly symptomatic subjects were enrolled following testing for SARS-COV-2. Fifty subjects tested negative, and 81 subjects tested positive. Serum samples were collected for measurement of C-reactive protein, ferritin, interleukin-6, NT-pro-B-type natriuretic peptide, and cardiac troponin 28–55 days after SARS-COV-2 RT-PCR testing.ResultsBiomarker levels trended higher in SARS-COV-2-positive vs negative subjects, but differences in biomarker levels or proportion of subjects with elevated biomarkers were not statistically significant with respect to SARS-COV-2 status. Among individuals with ≥ 1 comorbidity, odds of elevated CRP were greater compared to individuals without any comorbidities (odds ratio [OR] = 2.90); this effect size was increased 1.4-fold among SARS-COV-2-positive subjects (OR = 4.03). Similarly, NT-pro-BNP was associated with CVD, with the strongest association in COVID-positive individuals (OR = 16.9).ConclusionsIn a relatively young, healthy adult population, mild COVID-19 infection was associated with mild elevations in cardiac and proinflammatory biomarkers within 4–8 weeks of mild or asymptomatic COVID-19 infection in individuals with preexisting comorbidities, but not among individuals without comorbidities. For the general population of young adults, we did not find evidence of elevation of cardiac or proinflammatory biomarkers 4–8 weeks after COVID-19 infection.Clinical Perspective: This is a characterization of cardiac and proinflammatory biomarkers in ambulatory subjects following asymptomatic or mild COVID-19 infection. Young, ambulatory individuals did not have cardiac and proinflammatory biomarker elevation 4–8 weeks after mild COVID-19 infection. However, COVID-19 infection was associated with biomarker elevations in select individuals with comorbidities.Clinical study number: H-47423.