Prior COVID-19 Infection Research Articles

OP24 Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with Inflammatory Bowel Disease after three doses of COVID-19 vaccine: a prospective multicentre cohort study

Abstract Background Anti-tumour necrosis factor drugs such as infliximab are associated with attenuated antibody responses after COVID-19 vaccination. It is unknown how infliximab impacts vaccine-induced serological responses against highly transmissible Omicron variants, which possess the ability to evade host immunity and are now the dominating variants causing current waves of infection. Methods In this prospective, multicentre, observational cohort study, we investigated neutralising antibody responses against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants after three doses of COVID-19 vaccination in 1288 patients with IBD without prior COVID-19 infection, who were established on either infliximab (n=871) or vedolizumab (n=417). Cox proportional hazards models were constructed to investigate the risk of breakthrough infection in relation to neutralising antibody titres. Results Following three doses of COVID-19 vaccine, neutralising titre NT50 (half-inhibitory neutralising titre) was significantly diminished in patients treated with infliximab as compared to patients treated with vedolizumab, against wild-type, BA.1 and BA.4/5 variants (Fig 1). Patients with Crohn’s disease showed lower antibody NT50 compared to patients with ulcerative colitis against wild-type strain and BA.4/5 (Fig 2). Older age and thiopurine were independently associated with lower NT50 against wild-type strain and BA.4/5 (Fig 2). Non-white ethnicity was associated with higher NT50 compared to white ethnicity against wild-type strain, BA.1 and BA.4/5 (Fig 2). Breakthrough infection was significantly more frequent in patients treated with infliximab compared to patients treated with vedolizumab (Fig 3). Cox proportional hazards models of time to breakthrough infection after the third dose showed infliximab treatment to be associated with a higher hazard risk (HR) of 1.71 (95% CI [1.08 to 2.71], p=0.022) compared to vedolizumab (Fig 4). Higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and a longer time to breakthrough infection (HR 0.87 [0.79 to 0.95] p=0.0028) (Fig 4). Conclusion Following a third COVID-19 vaccine dose, patients established on infliximab treatment have significantly lower neutralising titres against SARS-CoV-2, which were especially low against Omicron variants. Increased breakthrough infection in infliximab recipients was associated with lower neutralising antibody titres against BA.4/5. These data underline the importance of continued COVID-19 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy may be reduced.

A Cross-Sectional Study to Assess mRNA-COVID-19 Vaccine Safety among Indian Children (5-17 Years) Living in Saudi Arabia.

The objective of this study is to assess the frequency and severity of adverse events following immunization (AEFI) in Indian children aged 5-17 years who received the Pfizer-BioNTech mRNA COVID-19 vaccine, as well as to investigate for predictors of AEFI. To examine AEFI following the first and second doses of Pfizer's vaccine, semi-structured questionnaires were distributed as Google forms at Indian schools in Saudi Arabia. The 385 responses included 48.1% male and 51.9% female children, with 136 responses of children aged 5-11 years (group A) and 249 responses from children aged 12-17 years (group B). Overall, 84.4% of children had two shots. The frequency of AEFI was reported to be higher after the first dose than after the second (OR = 2.12, 95% CI = 1.57-2.86). The reported AEFIs included myalgia, rhinitis, local reaction with fever, a temperature of 102 °F or higher, and mild to moderate injection site reactions. While group B frequently reported multiple AEFIs, group A typically reported just one. Local reaction with low grade fever was more frequently reported in group B after the first dose (24.1%) and second dose (15.4%), while local reaction without low grade fever was most frequently observed in group A after the first (36.8%) and second dose (30%). Only prior COVID-19 infection (OR = 2.98, 95% CI = 1.44-6.2) was associated with AEFI after the second dose in the study sample, whereas male gender (OR = 1.71, 95% CI = 1.13-2.6) and prior COVID-19 infection (OR = 2.95, 95% CI = 1.38-6.3) were predictors of AEFI after the first dose. Non-serious myocarditis was reported by only one child. According to the analysis conducted, the Pfizer's mRNA COVID-19 vaccination was found to be safe in Indian children.

Prior COVID-19 infection may increase risk for developing endothelial dysfunction following hematopoietic cell transplantation.

Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants.

Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults

BackgroundImmune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses.MethodsWe followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables.ResultsParticipants (n = 15) had median age of 90 years and mild, moderate, or severe frailty scores (n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status (p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty (p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses (p < 0.001), which was further impaired with higher frailty (p = 0.001). Notably, avidity increased to peak levels after the booster (p < 0.001). Overall antibody response was inversely correlated with a phenotype of immune-senescent T cells, CD8 + CD28- TEMRA cells (p = 0.036, adjusted for COVID-19 infection). Furthermore, there was increased detection of CD8 + CD28- TEMRA cells in individuals with greater frailty (p = 0.056, adjusted for COVID-19).ConclusionsWe evaluated the immune responses to the Moderna COVID-19 mRNA vaccine in frail older adults in a retirement community. A higher degree of frailty was associated with diminished antibody quantity and quality. However, a booster vaccine dose at 6 months overcame these effects. Frailty was associated with an increased immune-senescence phenotype that may contribute to the observed changes in the vaccine response. While the strength of our conclusions was limited by a small cohort, these results are important for guiding further investigation of vaccine responses in frail older adults.

Personal protective equipment usage among Iranian police officers during COVID-19 pandemic; a cross-sectional study

Objective: Due to the important role of police during COVID-19 pandemics and lack of previous studies on the impact of personal protective equipment (PPE) in reduction of COVID-19 infection among police officers, we aimed to investigate the role of using PPE in prevention of COVID-19 infection among Iranian police personnel.&#x0D; Methods: This cross-sectional survey was conducted in Tehran, Iran during January 2021 to November 2022. The study sample consisted of police personnel who were active in field operations. Demographics (age, height, weight, gender, marital status, number of children and underlying diseases) and job characteristics such as frequency and type of operations, involvement of colleagues with COVID-19, and COVID-19 infection history, using PPE, types of used PPE (mask, face shield, gloves, etc), protective strategies (such as social distancing) and COVID-19 vaccination were recorded. Statistical analysis was performed with IBM SPSS Statistics for Windows, version 25.&#x0D; Results: Totally, 340 participants were analyzed (33.54±9.74 years old, 91.2% males), of whom, 150 participants (44.1%) reported at least one episode of confirmed COVID-19 infection. The most common component of PPE used both during operations and daily life was face mask (44.7% and 75%, respectively). The most popular measure with higher adherence compared to others was social distancing with 70% popularity and an adherence score of 5.85±3.74. Three hundred subjects (88.2%) had received at least one dose of COVID-19 vaccine. Among PPE items, using face mask, washing hands with soap, social distancing and vaccination were significantly different between patients with and without prior COVID-19 infection (p&gt;0.05).&#x0D; Conclusion: The findings showed that use of PPE is significantly efficacious in reduction of COVID-19 infection among police officers. Therefore, despite difficulties of using PPE among police forces, it is strongly recommended for virus spread control in this population.

The Impact of Aerobic Exercise on Athletic Performance in Recovered and Uninfected COVID-19 Athletes during Post-COVID-19 Period

Background: The global COVID-19 pandemic has significantly influenced athletes worldwide. Objectives: This research aims to investigate the effects of a 4-week aerobic exercise program on athletic performance in both recovered and uninfected COVID-19 athletes during the post-COVID-19 period. Methods: Fourteen male student-athletes aged 18 - 25 years from Imam Khomeini International University participated in this study. The participants comprised 7 recovered COVID-19 athletes and 7 athletes with no prior COVID-19 infection. The study employed a pre-test/post-test design conducted in 2 phases. During the pre and post-test phases, participants underwent baseline assessments of athletic performance, including maximum oxygen consumption (VO2 max) and anaerobic power. Subsequently, the participants engaged in a 4-week aerobic exercise intervention. Pre- and post-intervention outcomes within groups were compared using paired t-tests, while independent t-tests were utilized for comparisons between the recovered COVID-19 athlete group and the uninfected athlete group. Results: Independent t-tests demonstrated significant increases in VO2 max and peak power after 4 weeks of aerobic exercise in both the recovered COVID-19 group (P = 0.001, P = 0.0001) and the uninfected COVID-19 group (P = 0.012, P = 0.001). However, dependent t-tests revealed a significant difference between the recovered COVID-19 group and the uninfected COVID-19 group in the post-test of VO2 max (P = 0.044) and peak power (P = 0.001). Conclusions: This study indicates that a 4-week aerobic exercise regimen can improve athletic performance in both recovered and uninfected COVID-19 athletes. However, recovered COVID-19 athletes exhibited a notably slower rate of improvement compared to their uninfected counterparts. Therefore, it is recommended that, in addition to aerobic exercise, recovered athletes integrate supplementary strategies to optimize their return-to-sport timeline and maximize performance recovery.

Corticosteroid-induced avascular bone necrosis and possible association with prior COVID-19 infection

Corticosteroid is a frequent implicating factor for the development of avascular bone necrosis (AVN). The etiology of corticosteroid-induced AVN is not fully understood, but it includes fat hypertrophy, fat embolism, and intravascular coagulation that causes obstruction of blood supply to the bone. This association can be carried forward for COVID-19 as well since it is also a microvascular disease. Suffering from COVID-19 and prescription of glucocorticoids could both be responsible for AVN. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease.

Значение герпесвирусов в постковидном периоде у детей

Aim: to assess the prevalence of detection of confirmed herpes virus infections (HVI) in children who had a previous COVID-19 infection, characterize specific clinical manifestations of the disease under the new conditions (post-COVID syndrome), and to provide a rationale for the administration of drug therapy. Patients and Methods: of 456 patients who received medical consultations from September 2021 to July 2022, the authors selected 72 (15.8%) children (42 boys and 30 girls) who had a previous SARS-CoV-2 infection confirmed by serological tests or polymerase chain reaction and in whom herpes viruses were found during serological evaluation. Results: most of the children (81.4%) visited the polyclinic within the first six months after the COVID-19 infection. Epstein-Barr virus (EBV) was the most prevalent finding among herpesviruses detected in children with post-COVID-19 sequela — it was detected in 44 (61.1%) cases. Human herpesvirus (HHV) 6 and cytomegalovirus (CMV) were less common in this group and found in 41 (56.9%) and 30 (41.7%) children, respectively. HHV-1 and HHV-2 were detected more rarely — in 11 (15.3%) children. Monoinfection was diagnosed in 41 (56.9%) cases and a combination of viruses was found in 31 children, in 22 (71.0%) of them it comprised two viruses, in 6 (19.3%) — three viruses, and in 3 (9.7%) — four viruses. The presence of herpesvirus infections underpinned the main reasons why parents of the ill children were seeking for outpatient care, in particular: a prolonged subfebrile condition (18.0%), fatigue and sleep disorders (27.7%), rashes (16.6%), lymphadenopathy (16.7%), ENT diseases (33.3%), more frequently occurring respiratory diseases (33.3%), and the increase in seizure activity in children with epilepsy (8.3%). In addition to herpes viruses, pathogenic agents were detected in 18% of patients, including intracellular pathogens, which were found in 13.9% of 72 children. Taking into consideration the obtained results and established clinical diagnoses, the authors conducted a review and provided a rationale for the administered drug therapy, including medications for herpes treatment. Conclusion: a prior COVID-19 infection induces immunosuppression and, as a result, the activation of herpesvirus infections as long-term effects of COVID-19 (post-COVID conditions). The presence of mixed viral and bacterial pathogens is an indication for administering antivirals, immunomodulators, antibacterial agents, and probiotics. KEYWORDS: post-COVID conditions, herpesvirus infections, children, clinical symptoms, treatment. FOR CITATION: Savenkova M.S., Sotnikov I.A., Afanasieva A.A. et al. Importance of herpes viruses in children with post-COVID conditions. Russian Journal of Woman and Child Health. 2023;6(1):39–44 (in Russ.). DOI: 10.32364/2618-8430-2023-6-1-39-44.

Utilization of Cardiovascular Magnetic Resonance Imaging for Resumption of Athletic Activities Following COVID-19 Infection: An Expert Consensus Document on Behalf of the American Heart Association Council on Cardiovascular Radiology and Intervention Leadership and Endorsed by the Society for Cardiovascular Magnetic Resonance.

The global pandemic of COVID-19 caused by infection with SARS-CoV-2 is now entering its fourth year with little evidence of abatement. As of December 2022, the World Health Organization Coronavirus (COVID-19) Dashboard reported 643 million cumulative confirmed cases of COVID-19 worldwide and 98 million in the United States alone as the country with the highest number of cases. Although pneumonia with lung injury has been the manifestation of COVID-19 principally responsible for morbidity and mortality, myocardial inflammation and systolic dysfunction though uncommon are well-recognized features that also associate with adverse prognosis. Given the broad swath of the population infected with COVID-19, the large number of affected professional, collegiate, and amateur athletes raises concern regarding the safe resumption of athletic activity (return to play) following resolution of infection. A variety of different testing combinations that leverage ECG, echocardiography, circulating cardiac biomarkers, and cardiovascular magnetic resonance imaging have been proposed and implemented to mitigate risk. Cardiovascular magnetic resonance in particular affords high sensitivity for myocarditis but has been employed and interpreted nonuniformly in the context of COVID-19 thereby raising uncertainty as to the generalizability and clinical relevance of findings with respect to return to play. This consensus document synthesizes available evidence to contextualize the appropriate utilization of cardiovascular magnetic resonance in the return to play assessment of athletes with prior COVID-19 infection to facilitate informed, evidence-based decisions, while identifying knowledge gaps that merit further investigation.

Individual and Work-Related Characteristics Associated with COVID-19 Vaccination Status among Ohio Nurses.

Uptake of the COVID-19 vaccine by nurses lags behind that of other health care professionals with minimal empirical evidence to understand this phenomenon. In this secondary analysis, we examined nurses' individual and work-related characteristics and their association with COVID-19 vaccination status. Alumni of three Ohio nursing colleges and members of a professional organization were invited to complete questionnaires from June through August 2021. Logistic regression models were used to evaluate associations between nurse characteristics and vaccination status. Among 844 respondents, 754 (80.30%) had received at least one dose of the vaccine. Older age, having a bachelor's degree or higher, and working in critical care were associated with vaccination. Providing direct care for COVID-19 patients in the last 7 days and a higher perception of one's work being affected by COVID-19 were significantly associated with being vaccinated, whereas prior COVID-19 infection was inversely associated with vaccination status. Our findings suggest that COVID-19 vaccine uptake among nurses is influenced by a host of factors related to virus knowledge, beliefs, and risk perceptions. Awareness of these factors can aid the development of interventions to increase nurses' acceptance of vaccines.

A Cross Sectional Study on Adherence to COVID Appropriate Behaviour and Contributing Factors among Vaccinated Individuals Attending ENT Out-Patient Department of a Teaching Hospital in India

Introduction With the commencement of mass vaccination drive globally against COVID-19 infection, the daily COVID appropriate behaviour may be neglected among the population. However the long term efficacy and safety of vaccines is not confirmatory yet. Hence the study was carried out to assess the post-vaccination COVID appropriate behaviour and contributing factors. Materials and Methods A cross-sectional study was conducted in the out-patient department of ENT of a teaching hospital in India from November 2021 to January 2022 among 448 vaccinated individuals. Face to face interview of the participants with a schedule was carried out for data collection. The data were analyzed by means of proportion and Chi-square test. Results More than 90% of the participants practiced greeting without physical contact, covering nose, mouth during coughing or sneezing, social distancing. But thorough hand washing technique was maintained by less than 75% of the respondents and post-vaccination mask use was reduced to around 68%. Participants of female gender, younger age group, with no history of prior COVID-19 infection were found to be more compliant with precautionary measures and significantly (p&lt;0.05) varied in relation to wearing facemasks and hand washing. Conclusion Thus regardless of the vaccination status, adherence to personal preventive behaviours is necessary to prevent the further spread of COVID-19 infection. It can be emphasized by the competent authority by maintaining some regulations and the same message can be disseminated by health education materials to the general population with special emphasis on high risk groups.

DETECTION OF RISK FACTORS AND PATIENT CHARACTERISTICS ASSOCIATED WITH MUCORMYCOSIS TO DESIGN SCREENING TOOLS HELPFUL IN PREVENTING ADVERSITIES AT PRIMARY CARE LEVEL: A CASE CONTROL STUDY

Background:Timely screening, early suspicion and accurate diagnostic measures are needed at primary care level to prevent catastrophe by events such as the recent and sudden emergence of COVID-19 associated mucormycosis (CAM). This entity which was observed during the second wave of this pandemic in India had caused severe chaos by its sudden appearance and frequent devastating outcomes. To identify the underlying risk factors, clinical characteri Objectives: stics and presentation in CAM cases enabling an early diagnostic approach by use of screening tools at primary care. A retrospect Methods: ive case-control study (April to June 2021) among those fullling the diagnostic criteria of mucormycosis with a prior COVID-19 infection. 50 patients with mucormycosis as cases and Results: 100 without as controls were enrolled in the study. The median duration from COVID-19 till the onset of CAM was 15 days. The mean age was 50 years and male preponderance, with most commonly reported infection sites nose and sinus (90%) and pansinusitis a predominant nding in CECT (contrast enhanced computed tomography). About 84% (42/50) CAM patients had diabetes mellitus and 60% had received corticosteroid treatment for COVID19. 13/50 (26%) cases had history of hypertensions. History of previous hospitalization was present in 60% (30/50) patients during COVID 19 infection and 26% patients had received oxygen therapy. Serum ferritin levels were available for 19, with elevated level s in 8/19 cases, 11/19 had normal range, 5/50 cases had received Remdesivir injection, only 10/50CAM patients had received a single dose of COVID-19 vaccine, others were non-vaccinated. Current study unveiled thatuncontrolled diabe Summary : tes mellitus and those who inadvertently receive corticosteroid therapy are at increased risk of CAM. With the ongoing pandemic and increasing number of CAM cases, patients positive for these risk factors during COVID management need regular screening at primary care level in order to prevent this deadly and often fatal secondary infection.

COVID-19 vaccine hesitancy and racial discrimination among US adults

Vaccination is a critical preventive measure to reduce COVID-19 health risks. We utilize full information maximum likelihood (FIML) logistic regression to analyze COVID-19 vaccine hesitancy in a national sample of United States (US) adults (N = 2,022). Online survey data was collected between September 7th and October 3rd, 2021. Before weighting, the racial composition of the sample was as follows: Asian American (15.0 %), Black/African American (20.0 %), Hispanic/Latino (20.0 %), American Indian or Alaska Native (12.6 %), Native Hawaiian or Pacific Islander (12.5 %), and White (20.0 %). Informed by the Increasing Vaccination Model (IVM), we assessed the relationship between COVID-19 vaccine hesitancy and experiences of racial discrimination (Krieger’s 9-item measure). Odds of COVID-19 vaccine hesitancy were greater for most younger age groups, women (OR = 1.96; 95 % CI[1.54, 2.49]), Black/African American respondents (OR = 1.68; 95 % CI[1.18, 2.39]), those with a high school education or less (OR = 1.46; 95 % CI[1.08, 1.98]), Independent (OR = 1.77; 95 % CI[1.34, 2.35]) or Republican political affiliation (OR = 2.69; 95 % CI[1.92, 3.79]), and prior COVID-19 infection (OR = 1.78; 95 % CI[1.29, 2.45]). Odds of COVID-19 vaccine hesitancy were 1.04 greater for every-one unit increase in lifetime experiences of racial discrimination (95 % CI[1.02, 1.05]). Odds of COVID-19 vaccine hesitancy were lower for Asian American respondents (OR = 0.682; 95 % CI[0.480, 0.969]), and those who had a primary care doctor had reduced odds of COVID-19 vaccine hesitancy (OR = 0.735; 95 % CI[0.542, 0.998). Our primary finding provides support for a link between experiences of racial discrimination and hesitancy towards a COVID-19 vaccine among US adults. We discuss implications for public health officials and future research.

Abstract #1324959: Graves’ Disease Post SARS-CoV-2 mRNA Vaccination: A Case Report and Literature Review

SARS-CoV-2 vaccinations resulted in a significant reduction in the transmission of COVID-19 infection, hospitalization, and mortality, yet it has been associated with the development and exacerbation of various autoimmune diseases, including thyroid autoimmune disorders. We report the new onset of Graves’ disease (GD) post-mRNA COVID vaccine in a patient with a background history of spontaneously recovered primary hypothyroidism and a prior COVID-19 infection.

SARS-CoV-2 Infection and Increased Risk for Pediatric Stroke

BackgroundThere is an increased risk of stroke in adults with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection, but whether there is a similar association with stroke in children is unclear. Our objective was to determine whether there is a correlation between COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and pediatric ischemic stroke. MethodsThis was a retrospective, population-based cohort analysis between March 1, 2020, and June 30, 2021, conducted at a children's hospital. Pediatric patients with a diagnosis of ischemic stroke were identified using ICD-10 diagnoses of ischemic stroke, cerebrovascular accident, or cerebral infarction. ResultsWe identified 16 patients, seven male and nine female, with ischemic stroke. Ages were 8 months to 17 years (median 11.5 years). More Asian (6%) and black (13%) patients had strokes compared with population prevalence (2% each, respectively). No patients had active COVID-19 infection. COVID-19 antibodies were identified in five of 11 patients tested (45%), of whom three were diagnosed with MIS-C. 82% of the strokes occurred between February and May 2021. The peak incidence was in February 2021, which was two months after peak incidence of pediatric cases of COVID-19 and one month after the peak of MIS-C cases. ConclusionsOur study suggests that prior COVID-19 infection, but not acute infection, is correlated with a risk for stroke in the pediatric population. The risk for stroke appears to be distinct from the risk for MIS-C.

COVID-19 Immune Response in Hematologic Malignancies: Analysis of COVID-19 Anti-Spike Antibodies in Previously Infected and Uninfected Patients

Patients with hematologic malignancies (HM) are immunocompromised and have worse clinical outcomes with COVID-19 infection than the general population. As previously reported (Niu et al. Leukemia Research 2021), this may in part be due to an altered immune system that is different from that of immunocompetent hosts. Therefore, it is imperative that patients with HM receive additional protection from COVID-19. However, with a distorted immune system, the question of whether patients with HM can mount an appropriate antibody response (AAR) is unknown. Here, we evaluated the antibody response to the COVID-19 vaccine in previously infected and uninfected patients with HM. From 3/31/20 to 05/31/22, we examined 400 patients (age 18 to 86), 120 of which had a HM (58 lymphoid, 53 multiple myeloma, and 9 myeloid), 58 had a solid malignancy (SM), and 222 were controls (without a HM or SM). These 400 patients had their 1st and 2nd vaccinations, 3rd vaccination/booster, and 4th vaccination/2nd booster, (if all or any were applicable) documented. Following informed consent in accordance with the Declaration of Helsinki and IRB approval, blood draws were obtained with respect to each vaccination and/or booster date to assess antibody response. To standardize antibody response in this analysis, only patients that had antibodies collected after 90 days from their specific vaccination/booster were analyzed. The main antibodies evaluated were the SARS-CoV-2 virus antibodies toward spike proteins (anti-spike). Anti-N and anti-S antibodies were also obtained for future analysis. An AAR was determined to be an anti-spike level of greater than 0.5. If patients had a positive anti-S response (>0.5), they were considered as having been previously infected regardless of clinical history. In patients without prior COVID-19 infection, analysis of antibody levels post-1st vaccination showed all evaluated control patients (5 of 5) as developing an AAR, while only 1 of 7 HM patients and 1 of 2 SM patients developed an AAR. Analysis after the 2nd vaccination showed most control patients (27 of 28) developing an AAR and all patients with SM developing an AAR (9 of 9). However, only 50% of HM patients developed an antibody response (14 of 27). After the 3rd injection/booster, all control group patients (18 of 18), all SM patients (6 of 6), and most HM patients (13 of 14) developed an AAR (Fig 1). A subgroup analysis for the post-dose 2 vaccination in HM patients found that for non-multiple myeloma lymphoid malignancies, 5 of 11 patients didn't develop an AAR. 4 of these patients had received treatment for their underlying malignancy within 3 months of the vaccine. For the 6 responders, 5 of these patients were not on any treatment. In patients with prior COVID-19 infection, post-1st vaccination analysis showed almost all control patients as developing an AAR (9 of 10) while 4 of 5 patients with HM responded. No SM patients were collected. After the 2nd vaccination, all control patients (71) and all HM patients (20) had an AAR, while 11 of 12 SM patients had an AAR. Following the 3rd injection/booster, all evaluated patients (33 control, 7 HM, and 3 SM) had an AAR (Fig 2). Our evaluation of anti-spike antibodies in response to the COVID-19 vaccine in patients with HM, showed that this specific group responded differently than the general population or those with SM. In our uninfected cohort, only half of the evaluated HM patients had an AAR after the 2nd vaccination, while most control and SM patients had the desired response. In comparison, HM patients who had a COVID-19 infection developed an AAR after their 2nd vaccination. This indicates that patients with HM likely require additional immune activation before achieving an AAR. Close to half of HM patients in the uninfected cohort required 3 vaccine doses to achieve an AAR. In previously COVID-19 infected HM patients, the majority were able to achieve an AAR after 2 vaccinations, indicating exposure to the virus may have helped provide additional immunity. Thus, as the landscape of the COVID-19 pandemic is constantly shifting, the current guideline of vaccines and their efficacy in immunocompromised patients is something that will need to be consistently addressed. As more data is collected on our cohort of patients, we will track the longitudinal antibody responses (anti-spike, anti-N, and anti-S) for each patient over time, overall trends of antibody response after the 4th vaccination, and T-cell responses. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Patients with Monoclonal Gammopathy Have a High Rate of Second Symptomatic COVID-19 Infection Even after a Prior COVID-19 Infection and Vaccination

Background: Patients with hematologic malignancies, including multiple myeloma (MM), light chain (AL) amyloidosis, smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS), have disproportionately high rates of COVID-19 infection and associated mortality. While inferior immune response to COVID-19 vaccination have been described in patients with monoclonal gammopathy, information on the rate and severity of COVID-19 infections in patients who do demonstrate immunogenicity after a prior infection or vaccination is limited. Additionally, the prevalence and clinical course of second symptomatic COVID-19 infections in patients with monoclonal gammopathy is not known. Methods: Patients with MGUS, SMM, MM or AL amyloidosis evaluated at Mayo Clinic Rochester, Arizona, and Florida between 12/01/2019 and 8/31/2021 were screened. Patients with a positive polymerase chain reaction test for SARS-CoV-2 and either a spike Ab (Ab) or a nucleocapsid Ab tested were included. Spike Ab was reported quantitatively (positive result >0.8 IU/mL per laboratory standard) and nucleocapsid Ab testing was reported as either positive or negative. For this study, we defined "fully vaccinated” as 2 doses of Pfizer or Moderna mRNA vaccine or 1 dose of the Janssen vaccine based on the prevalent CDC recommendation during the study period. Patients with a 2nd symptomatic COVID-19 infection had an interim negative COVID-19 test result with complete clinical recovery. Results: Out of 19,943 patients with an underlying monoclonal gammopathy, 483 patients (2.4%) had a documented positive COVID-19 PCR test and 101 patients had COVID-19 antibody testing performed [spike Ab=54, nucleocapsid Ab=47]. The baseline characteristics of these 101 patients are depicted in Table 1. Out of the 101 patients, 13 (13%) developed a 2nd symptomatic COVID-19 infection. Details of the timeline for second infections in relation to vaccination, antibody testing and ongoing treatment are depicted in Figure 1. The majority of 2nd COVID-19 were mild (11/13, 85%) and the 2 patients (15%) with a severe 2nd infection were both unvaccinated. The median time to 2nd infection was 6.3 months (range 1-19 months) from the 1st COVID-19 infection. Of the 42 patients with MM/AL, 25 patients were in remission and 1 out of these 25 (4%) patients developed a 2nd COVID-19 infection. Compared to patients in remission, 5 (29%) of the 17 patients with MM/AL not in remission developed a 2nd infection (p=0.03). Rate of 2nd infection was 21% (6/28) in unvaccinated patients compared to 10% (7/73) in patients after completion of initial vaccination series (p=0.11). Six out of the 7 vaccinated patients had received a third dose of vaccination prior to the 2nd infection. Among the 382 patients in whom an antibody test was not performed, 22 (6%) patients developed a second infection out of which 3 (14%) were severe. Out of 101 patients, 85 patients were unvaccinated at the time of first infection and 63 (74%) developed a positive COVID-19 Ab after the 1st symptomatic infection (spike Ab n=38, nucleocapsid Ab n=25). Out of these 63 patients with seropositivity, 7 (11%) developed a second symptomatic COVID-19 infection at a median time of 9.9 months (range 2.9-19.6) from first COVID-19 infection and 6 (range 2-18.7) months from the time of antibody testing. To assess seropositivity after vaccination, spike Ab was used as nucleocapsid Ab can be negative after mRNA vaccination. Among the vaccinated patients at the time of first infection (n=16), 6 had a spike Ab tested before 1st COVID-19 infection at a median of 65 (range 16-109) days from vaccination. Of these, 5 (83%) demonstrated a positive spike Ab response to the vaccination. Despite seropositivity, all 5 developed COVID-19 and 2 patients with positive spike Ab developed a severe 1st COVID-19 infection (without mortality) at 84 days and 99 days from vaccination, respectively [spike Ab level was 145 IU/mL and > 250 IU/mL, respectively]. None of the vaccinated and seropositive patients (n=10) developed a 2nd symptomatic COVID-19 infection. Conclusion: Patients with an underlying MM, AL or MGUS demonstrate a substantial risk for second symptomatic COVID-19 infections suggesting a rapidly waning immunity. Most of the 2nd COVID-19 infections were mild, with severe infections restricted to the unvaccinated population. Patients in whom underlying MM or AL was in remission was protective against a 2nd infection. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Protection Against Breakthrough Delta/Omicron Variants in Vaccinated Patients with Myeloproliferative Neoplasms (MPN)

Background Information on breakthrough SARS-CoV-2 infections in MPN vaccinated patients (pts) is very limited. In these diseases, effectiveness of coronavirus disease 2019 (Covid-19) vaccines may be influenced not only by the MPN phenotype and the intrinsic reduced immunological competence, but also by the prior Covid-19 infection that can elicit a natural immunity against reinfections. Patients In the European LeukemiaNet (ELN) observational registry, 863 MPN pts with Covid-19 have been enrolled since February 2020 and in 649 of them, information on the vaccination status is now available. To ensure that well characterized reinfections were considered, diagnosis of breakthrough Covid-19 included a positive naso-pharyngeal swab and symptoms highly suggestive for SARS CoV-2 infection. ResultsBreakthrough infections in vaccinated patients with previous Covid-19 infection The effectiveness of previous Covid-19 infection in preventing reinfections was tested in a group of 131 and 287 unvaccinated and vaccinated MPN pts, respectively. Prior Covid-19 occurred during the first and second wave in 74% and 98% pts, respectively and the interval between Covid-19 and the breakthrough infection in unvaccinated and in vaccinated was similar (8.5 months). Administered vaccine doses (Pfizer in 71%) were 1-2 and 3-4 in 77% and 23% of vaccinated cases, respectively. The proportion of PV, ET, pre-PMF was similar in the two groups while the number of MF pts was lower (19%) than in the unvaccinated group (28%) (p=0.024). Reinfections occurred during delta (n=4) or omicron variants period (n=14) in 8 (6.1%) and 10 (3.5%) unvaccinated and vaccinated pts (p=ns) and hospitalization was required in 0 and 2 pts, respectively. Severity of the acute infection was variable and 1 death was registered.Breakthrough infections in vaccinated patients without previous Covid-19 infection Breakthrough infections were reported in 231 vaccinated cases (ET=89, PV=75, MF=54 and pre-PMF=13) without prior Covid-19. In 51% of pts the administered vaccine doses were 1-2 and 3-4 in 49%. No relevant vaccine related side effects were registered. Time interval from vaccination to Covid-19 was 8.1 months. Twenty-six pts (11%) required hospitalization and 205 (89%) were managed at home. Hospitalized pts were older (median age 76), males (69%) with MF (39%), and prior exposure to ruxolitinib (42%, 7 MF and 4 PV). Of note, values of C-reactive protein (CRP) and neutrophil/lymphocyte ratio (NLR) were significantly more elevated in hospitalized cases (CRP=33.1 vs. 2.0 and NLR=5.9 vs. 3.3, p<0.001). Although some infections occurred in the second wave, corresponding to alpha/beta/gamma coronavirus infection (6%), the majority of breakthrough episodes occurred in delta and omicron variant periods (41% and 53%). Three deaths were registered in hospitalized pts. We explored the risk of hospitalization and evaluated the marginal effect of gender, age and ruxolitinib exposure in a logistic model fitted to predict this event. We found that the risk of hospitalization was substantially higher only in males on ruxolitinib and increased with age (Figure). We also found that the inflammatory status measured with NLR could explain these results (data not shown). Conclusion The effectiveness of previous Covid-19 in preventing reinfection occurring during the delta and omicron variants of SARS-CoV-2 was robust (94% and 97% in unvaccinated and vaccinated pts, respectively). This is good news for MPN patients who recovered from Covid-19 and the hope is that this effectiveness can work against any future SARS-CoV-2 variant. In the cohort of vaccinated pts without prior Covid-19, we identified a subgroup of patients with more severe delta and omicron disease, at high risk of hospitalization, consisting of males who were on ruxolitinib and had elevated inflammatory biomarkers. Subsequent studies are needed to interpret these latest results. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Utility of a Digital Therapeutic Intervention in Indian Patients With Type 2 Diabetes Mellitus: 12-Week Prospective Single-Arm Intervention Study.

Patients with type 2 diabetes mellitus (T2DM) having elevated levels of blood glucose and glycated hemoglobin (HbA1c) are at higher risk of macro- and microvascular complications. Nonetheless, the goal of achieving glycemic control cannot be met with the use of pharmacotherapy alone. The recent emergence of digital therapeutic tools has shown the possibility of improving the modifiable risk factors and self-management of diabetes. The aim of this study was to examine the clinical utility of a digital therapeutic intervention as an add-on therapy to achieve glycemic control in patients with T2DM. This was a 12-week prospective, single-arm digital intervention study in patients with T2DM receiving regular antidiabetic treatment. The eligibility criteria included male and female patients with HbA1c≥6.5%, functional English literacy, and a mobile phone capable of running the intervention app. Outcome measures of the study were mean changes in HbA1c, fasting blood glucose (FBG), postprandial blood glucose (PPBG), BMI, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index at the end of 12 weeks. A total of 128 participants completed the study period of 12 weeks. There were 54.7% (70/128) men and 45.3% (58/128) women with a mean age of 48.48 years (SD 10.27). At the end of 12 weeks, the mean change in HbA1c, FBG, PPBG, and BMI for the overall study population was -0.84% (P<.001), -8.39 mg/dl (P=.02), -14.97 mg/dl (P<.001), and -0.24 kg/m2 (P=.06), respectively. Among the participants showing improvement in the HbA1c value at the end of 12 weeks (responders), the mean change in HbA1c, FBG, PPBG, and BMI was -1.24% (P<.001), -12.42 mg/dl (P=.003), -21.45 mg/dl (P<.001), and -0.34 kg/m2 (P=.007), respectively. There was an increase in HOMA-IR values for the overall study population (0.54, P=.29). HbA1c response showed a significant association with a baseline HbA1c level ≥7.5%, no prior history of smoking, and no prior COVID-19 infection, as well as with higher levels of program engagement. A digital therapeutic intervention when used alongside standard medications significantly reduces HbA1c, FBG, and PPBG levels in patients with T2DM.

The perfect storm: Thrombotic thrombocytopenic purpura (TTP) associated with COVID-19, a clinical case series and review.

This is a case series of three patients in our hospital system who developed acquired thrombotic thrombocytopenic purpura (aTTP) after testing positive for COVID-19 infection. Two patients had acute COVID-19 infections, and one had COVID-19 IgG antibodies consistent with prior COVID-19 infection. Twelve additional cases of aTTP after COVID-19 infection were found in the literature. COVID-19 creates alterations in the vWF-ADAMTS-13 axis with reduced ADAMTS-13 in acute illness that may lead those patients who are predisposed into fulminant aTTP. Further genetic studies are necessary to uncover why some patients with COVID-19 can have concurrent aTTP. For those with a prior COVID-19 infection, molecular mimicry with autoantibodies to ADAMTS-13 is likely the predominant trigger, but having an underlying predisposition (prior episode of TTP, genetic predisposition to autoimmune conditions, or breast cancer history) creates an environment that could be a possible trigger for aTTP.