Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection's symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute B-lymphoblastic leukemia before achieving viral clearance. Shortly before their scheduled allogeneic HSCT from a matched unrelated donor, the patient developed mild Omicron BA.5 infection receiving nirmatrelvir/ritonavir with fever resolution within 72 hours. Twenty-three days after COVID-19 diagnosis, because of increasing minimal residual disease values in the context of high-risk refractory leukemia and clinical resolution of SARS-2-CoV infection with reduction of viral load at surveillance nasopharyngeal swabs, it was decided not to delay further allo-HSCT. During myelo-ablative conditioning, the nasopharyngeal SARS-CoV-2 viral load increased while the patient remained asymptomatic. Consequently, two days before the transplant, intra-muscular tixagevimab/cilgavimab 300/300 mg and a 3-day course of intravenous remdesivir were administered. During the pre-engraftment phase, veno-occlusive disease (VOD) occurred at day +13, requiring defibrotide treatment to obtain a slow but complete recovery. The post-engraftment phase was characterized by mild COVID-19 at day +23 (cough, rhino-conjunctivitis, fever) that spontaneously resolved, achieving viral clearance at day +28. At day +32, she experienced grade I acute graft-versus host disease (a-GVHD, skin grade II) treated with steroids and photo-apheresis, without further complications during follow-up until day +180. Addressing the issue of allo-HSCT timing in patients recovering from SARS-CoV-2 infection with high-risk malignant diseases is challenging because of 1] the high risk of COVID-19 clinical progression, 2] the impact of transplant delay on leukemia prognosis and 3] the occurrence of endothelial complications such as VOD, a-GVHD, and transplant associated thrombotic micro-angiopathy. Our report describes the favourable outcome of allo-HSCT in a recipient with active SARS-CoV2 infection and high-risk leukemia thanks to timely anti-SARS-CoV-2 preventive therapies and prompt management of transplant-related complications.

Detection of specific RBD+ IgG+ memory B cells by flow cytometry in healthcare workers and patients with inborn errors of immunity after BNT162b2 m RNA COVID-19 vaccination.

Introduction: Inborn errors of immunity (IEI) are a heterogeneous group of diseases caused by intrinsic defects of the immune system. Estimating the immune competence of immunocompromised patients for an infection risk assessment or after SARS-CoV-2 vaccination constituted a challenge. Methods: The aim of this study was to determine the humoral responses of patients with IEI through a comprehensive analysis of specific receptor-binding domain-positive (RBD+) IgG+ memory B cells (MBCs) by flow cytometry, together with routine S-specific IgG antibodies and QuantiFERON SARS-CoV-2 (T-cell response), before the vaccine and 3 weeks after a second dose. Results and discussion: We first analyzed the percentage of specific RBD+ IgG+ MBCs in healthy healthcare workers. Within the control group, there was an increase in the percentage of specific IgG+ RBD+ MBCs 21 days after the second dose, which was consistent with S-specific IgG antibodies.Thirty-one patients with IEI were included for the pre- and post-vaccination study; IgG+ RBD+ MBCs were not evaluated in 6 patients due to an absence of B cells in peripheral blood. We detected various patterns among the patients with IEI with circulating B cells (25, 81%): an adequate humoral response was observed in 12/25, consider by the detection of positive S-specific IgG antibodies and the presence of specific IgG+ RBD+ MBCs, presenting a positive T-cell response; in 4/25, very low S-specific IgG antibody counts correlated with undetectable events in the IgG+ RBD+ MBC compartment but with positive cellular response. Despite the presence of S-specific IgG antibodies, we were unable to detect a relevant percentage of IgG+ RBD+ MBCs in 5/25; however, all presented positive T-cell response. Lastly, we observed a profound failure of B and T-cell response in 3 (10%) patients with IEI, with no assessment of S-specific IgG antibodies, IgG+ RBD+ MBCs, and negative cellular response. The identification of specific IgG+ RBD+ MBCs by flow cytometry provides information on different humoral immune response outcomes in patients with IEI and aids the assessment of immune competence status after SARS-CoV-2 mRNA vaccine (BNT162b2), together with S-specific IgG antibodies and T-cell responses.

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection.

Background: The cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection. Methods: Sixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models. Results: Data suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively. Conclusion: This pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.

Evolution of antibody profiles against SARS-CoV-2 in experienced and naïve vaccinated elderly people.

Introduction: The third dose of the COVID-19 vaccine is especially necessary in people over 65 years of age due to their lower immune response. Methods: We designed a multicentre, prospective observational study including 98 people ≤65 years old who lived in two nursing homes in Valladolid, Spain. One of the groups had previous experience with SARS-CoV-2 (n=68;69.4%) and the other was naïve (n=30;30.6%). We evaluated the response to the three doses of the Comirnaty vaccine and the dynamics of antibodies during 5 consecutive serum samplings: 2 after the first two doses of vaccination, one three months after the first dose, another at 6 months and the last one month after the third dose. IgG antibodies against SARS-CoV-2 S1, RBD and N antigens were analysed. Results: Both groups increased the level of Abs against S1 and RBD, but the experienced group showed a 130-fold higher humoral response due to hybrid immunisation (infection+vaccination). The response to vaccination with Comirnaty against COVID-19 was higher in those ≤65 years with previous experience than those who were naïve. However, the amount of antibodies against S1 and RBD equalised at 6 months. After the third dose, both groups raised the amount of antibodies to a similar level. The reinfections suggested by the analysis of antibodies against N were frequent in both groups. Discussion: The third dose showed a clear benefit for elderly people, with the reinforcement of the antibody levels after the decline suffered after six months of the first two doses.

Fast, cheap and sensitive: Homogenizer-based RNA extraction free method for SARS-CoV-2 detection by RT-qPCR.

Background: The SARS-CoV-2 gold standard detection method is an RT-qPCR with a previous step of viral RNA extraction from the patient sample either by using commercial automatized or manual extraction kits. This RNA extraction step is expensive and time demanding. Objective: The aim of our study was to evaluate the clinical performance of a simple SARS-CoV-2 detection protocol based on a fast and intense sample homogenization followed by direct RT-qPCR. Results: 388 nasopharyngeal swabs were analyzed in this study. 222 of them tested positive for SARS-CoV-2 by the gold standard RNA extraction and RT-qPCR method, while 166 tested negative. 197 of those 222 positive samples were also positive for the homogenization protocol, yielding a sensitivity of 88.74% (95% IC; 83.83 - 92.58). 166 of those negative samples were also negative for the homogenization protocol, so the specificity obtained was 97% (95% IC; 93.11 - 99.01). For Ct values below 30, meaning a viral load of 103 copies/uL, only 4 SARS-CoV-2 positive samples failed for the RNA extraction free method; for that limit of detection, the homogenizer-based method had a sensitivity of 97.92% (95% CI; 96.01 - 99.83). Conclusions: Our results show that this fast and cheap homogenization method for the SARS-CoV-2 detection by RT-qPCR is a reliable alternative of high sensitivity for potentially infectious SARS-CoV-2 positive patients. This RNA extraction free protocol would help to reduce diagnosis time and cost, and to overcome the RNA extraction kits shortage experienced during COVID-19 pandemic.

Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines.

Background: Immunity acquired from natural SARS-CoV-2 infection and vaccine wanes overtime. This longitudinal prospective study compared the effect of a booster vaccine (BNT162b2) in inducing the mucosal (nasal) and serological antibody between Covid-19 recovered patients and healthy unexposed subjects with two dose of mRNA vaccine (vaccine-only group). Method: Eleven recovered patients and eleven gender-and-age matched unexposed subjects who had mRNA vaccines were recruited. The SARS-CoV-2 spike 1 (S1) protein specific IgA, IgG and the ACE2 binding inhibition to the ancestral SARS-CoV-2 and omicron (BA.1) variant receptor binding domain were measured in their nasal epithelial lining fluid and plasma. Result: In the recovered group, the booster expanded the nasal IgA dominancy inherited from natural infection to IgA and IgG. They also had a higher S1-specific nasal and plasma IgA and IgG levels with a better inhibition against the omicron BA.1 variant and ancestral SARS-CoV-2 when compared with vaccine-only subjects. The nasal S1-specific IgA induced by natural infection lasted longer than those induced by vaccines while the plasma antibodies of both groups maintained at a high level for at least 21 weeks after booster. Conclusion: The booster benefited all subjects to obtain neutralizing antibody (NAb) against omicron BA.1 variant in plasma while only the Covid-19 recovered subjects had an extra enrichment in nasal NAb against omicron BA.1 variant.

Persistent humoral and CD4+ TH cell immunity after mild SARS-COV-2 infection-The CoNAN long-term study.

Understanding persistent cellular and humoral immune responses to SARS-CoV-2 will be of major importance to terminate the ongoing pandemic. Here, we assessed long-term immunity in individuals with mild COVID-19 up to 1 year after a localized SARS-CoV-2 outbreak. CoNAN was a longitudinal population-based cohort study performed 1.5 months, 6 months, and 12 months after a SARS-CoV-2 outbreak in a rural German community. We performed a time series of five different IgG immunoassays assessing SARS-CoV-2 antibody responses on serum samples from individuals that had been tested positive after a SARS-CoV-2 outbreak and in control individuals who had a negative PCR result. These analyses were complemented with the determination of spike-antigen specific TH cell responses in the same individuals. All infected participants were presented as asymptomatic or mild cases. Participants initially tested positive for SARS-CoV-2 infection either with PCR, antibody testing, or both had a rapid initial decline in the serum antibody levels in all serological tests but showed a persisting TH cell immunity as assessed by the detection of SARS-CoV-2 specificity of TH cells for up to 1 year after infection. Our data support the notion of a persistent T-cell immunity in mild and asymptomatic cases of SARS-CoV-2 up to 1 year after infection. We show that antibody titers decline over 1 year, but considering several test results, complete seroreversion is rare. Trial registration: German Clinical Trials Register DRKS00022416.

Are preterm birth and very low birth weight rates altered in the early COVID (2020) SARS-CoV-2 era?

Objective: We evaluated the prevalence of preterm birth (PTB) and very low birth weight (VLBW) during Jan-Dec 2,020 (early COVID era) at 5 hospitals (2 in West Virginia, 3 in California) compared to Jan 2017-Dec 2019 (pre-COVID) inclusive of 2 regional perinatal centers (1 in Huntington, WV and 1 in San Jose, CA) and 3 community hospitals (1 each in Cabell, Los Angeles and Santa Clara counties). Design/methods: We examined PTB and VLBW rates of live births at 5 US hospitals from Jan 2017-Dec 2020. We compared PTB and VLBW rates in 2020 to 2017-2019 using Poisson regression and rate ratio with a 95% confidence interval. We stratified live births by gestational age (GA) (<37, 33-36, and <33 weeks) and birth weight (≤1,500 g, >1,001 g to ≤1,500 g, ≤1,000 g). We examined PTB rates at 4 of the hospitals during Jan-Dec 2020 and compared them to the prior period of Jan 2017-Dec 2019 using Statistical Process Control (SPC) for quarterly data. Results: We examined PTB and VLBW rates in 34,599 consecutive live births born Jan 2017-Dec 2019 to rates of 9,691 consecutive live births in 2020. There was no significant change in PTB (<37 weeks GA) rate, 10.6% in 2017-2019 vs. 11.0% in 2020 (p = 0.222). Additionally, there was no significant change when comparing VLBW rates in 2017-2019 to 2020, 1.4% in 2017-2019 vs. 1.5% in 2020 (p = 0.832). Conclusion: We found no significant change in the rates of PTB or VLBW when combining the live birth data of 5 US hospitals in 3 different counties.

Three doses of BNT162b2 COVID-19 mRNA vaccine establish long-lasting CD8+ T cell immunity in CLL and MDS patients.

Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection-related disease and mortality. To understand T cell immunity, its long-term persistence, and its correlation with antibody response, we evaluated the BNT162b2 COVID-19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine-specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cells was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 mRNA vaccine-derived immunogenic responses were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group.

Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls.

Severe respiratory viral infections, including SARS-CoV-2, have resulted in high mortality rates despite corticosteroids and other immunomodulatory therapies. Despite recognition of the pathogenic role of neutrophils, in-depth analyses of this cell population have been limited, due to technical challenges of working with neutrophils. We undertook an unbiased, detailed analysis of neutrophil responses in adult patients with COVID-19 and healthy controls, to determine whether distinct neutrophil phenotypes could be identified during infections compared to the healthy state. Single-cell RNA sequencing analysis of peripheral blood neutrophils from hospitalized patients with mild or severe COVID-19 disease and healthy controls revealed distinct mature neutrophil subpopulations, with relative proportions linked to disease severity. Disruption of predicted cell-cell interactions, activated oxidative phosphorylation genes, and downregulated antiviral and host defense pathway genes were observed in neutrophils obtained during severe compared to mild infections. Our findings suggest that during severe infections, there is a loss of normal regulatory neutrophil phenotypes seen in healthy subjects, coupled with the dropout of appropriate cellular interactions. Given that neutrophils are the most abundant circulating leukocytes with highly pathogenic potential, current immunotherapies for severe infections may be optimized by determining whether they aid in restoring an appropriate balance of neutrophil subpopulations.

Pituitary apoplexy and COVID-19 vaccination: a case report and literature review.

A 50-year-old man was admitted to our hospital for vomit, nausea, diplopia, and headache resistant to analgesic drugs. Symptoms started the day after his third COVID-19 mRNA vaccine (Moderna) whereas SARS-CoV-2 nasal swab was negative. Pituitary MRI showed recent bleeding in macroadenoma, consistent with pituitary apoplexy. Adverse Drug Reaction was reported to AIFA (Italian Medicines Agency).A stress dexamethasone dose was administered due to the risk of adrenal insufficiency and to reduce oedema. Biochemistry showed secondary hypogonadism; inflammatory markers were elevated as well as white blood cells count, fibrinogen and D-dimer. Pituitary tumour transsphenoidal resection was performed and pathology report was consistent with pituitary adenoma with focal haemorrhage and necrosis; we found immunohistochemical evidence for SARS-CoV-2 proteins next to pituitary capillaries, in the presence of an evident lymphocyte infiltrate.Few cases of pituitary apoplexy after COVID-19 vaccination and infection have been reported. Several hypotheses have been suggested to explain this clinical picture, including cross-reactivity between SARS-CoV-2 and pituitary proteins, COVID-19-associated coagulopathy, infection-driven acutely increased pituitary blood demand, anti-Platelet Factor 4/heparin antibodies development after vaccine administration. Ours is the first case of SARS-CoV-2 evidence in pituitary tissue, suggesting that endothelial infection of pituitary capillaries could be present before vaccination, possibly due to a previous asymptomatic SARS-CoV-2 infection. Our case underlines that SARS-CoV-2 can associate with apoplexy by penetrating the central nervous system, even in cases of negative nasal swab. Patients with pituitary tumours may develop pituitary apoplexy after exposure to SARS-CoV-2, therefore clinicians should be aware of this risk.

Survival and detection of SARS-CoV-2 variants on dry swabs post storage.

COVID-19 has resulted in nearly 598 million infections and over 6.46 million deaths since the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2019. The rapid onset of the pandemic, combined with the emergence of viral variants, crippled many health systems particularly from the perspective of coping with massive diagnostic loads. Shortages of diagnostic kits and capacity forced laboratories to store clinical samples resulting in huge backlogs, the effects of this on diagnostic pickup have not been fully understood. Herein, we investigated the impact of storing SARS-CoV-2 inoculated dry swabs on the detection and viability of four viral strains over a period of 7 days. Viral load, as detected by qRT-PCR, displayed no significant degradation during this time for all viral loads tested. In contrast, there was a ca. 2 log reduction in viral viability as measured by the tissue culture infectious dose (TCID) assay, with 1-3 log viable virus detected on dry swabs after 7 days. When swabs were coated with 102 viral copies of the Omicron variant, no viable virus was detected after 24 hours following storage at 4°C or room temperature. However there was no loss of PCR signal over 7 days. All four strains showed comparable growth kinetics and survival when cultured in Vero E6 cells. Our data provide information on the viability of SARS-CoV-2 on stored swabs in a clinical setting with important implications for diagnostic pickup and laboratory processing protocols. Survival after 7 days of SARS-CoV-2 strains on swabs with high viral loads may impact public health and biosafety practices in diagnostic laboratories.

Inflammatory-Metal Profile as a Hallmark for COVID-19 Severity During Pregnancy.

Pregnancy makes women more susceptible to infectious agents; however, available data on the effect of SARS-CoV-2 on pregnant women are limited. To date, inflammatory responses and changes in serum metal concentration have been reported in COVID-19 patients, but few associations between metal ions and cytokines have been described. The aim of this study was to evaluate correlations between inflammatory markers and serum metal ions in third-trimester pregnant women with varying COVID-19 disease severity. Patients with severe symptoms had increased concentrations of serum magnesium, copper, and calcium ions and decreased concentrations of iron, zinc, and sodium ions. Potassium ions were unaffected. Pro-inflammatory cytokines IL-6, TNF-α, IL-8, IL-1α, anti-inflammatory cytokine IL-4, and the IP-10 chemokine were induced in the severe presentation of COVID-19 during pregnancy. Robust negative correlations between iron/magnesium and zinc/IL-6, and a positive correlation between copper/IP-10 were observed in pregnant women with the severe form of the disease. Thus, coordinated alterations of serum metal ions and inflammatory markers - suggestive of underlying pathophysiological interactions-occur during SARS-CoV-2 infection in pregnancy.

Long pentraxin 3 (PTX3) levels predict death, intubation and thrombotic events among hospitalized patients with COVID-19.

Background: PTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19. Methods: Levels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method. Results: Upon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P<0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P<0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median [IQR]: 51.4 [24.6-94.4] versus 21 [13.4-55.2]; P=0.049). Conclusions: High PTX3 levels in patients hospitalized with COVID-19 are associated with a worse outcome. The evaluation of this marker could be useful in prognostic stratification and identification of patients who could benefit from immunomodulant therapy.

Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

The need for more holistic immune profiling in next-generation SARS-CoV-2 vaccine trials.

First-generation anit-SARS-CoV-2 vaccines were highly successful. They rapidly met an unforeseen emergency need, saved millions of lives, and simultaneously eased the burden on healthcare systems worldwide. The first-generation vaccines, however, focused too narrowly on antibody-based immunity as the sole marker of vaccine trial success, resulting in large knowledge gaps about waning vaccine protection, lack of vaccine robustness to viral mutation, and lack of efficacy in immunocompromised populations. Detailed reviews of first-generation vaccines, including their mode of action and geographical distribution, have been published elsewhere. Second-generation clinical trials must address these gaps by evaluating a broader range of immune markers, including those representing cell-mediated immunity, to ensure the most protective and long-lasting vaccines are brought to market.

Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic.

Background: The COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact. Methods: A Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention. Results: Analysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0-21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p < 0.001) and inability to obtain therapies (p < 0.001) and surgeries (p < 0.001). Guardian responses from CARD had increased reports of worsening behavior (p = 0.01). Providers increased availability of in-person and virtual therapies and visits and made referrals for additional care to address this. In a survey of medical providers, five out of six program directors who received the responses to this survey found this questionnaire helpful in caring for their patients. Conclusion: This quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result.