Immunogenetic studies on SARS-CoV-2: Our experience at SKIMS

Background: The pathophysiology of viral-infections is highly complex and involves host immunocompetence, host genetics, and gene-environment interactions. We hypothesized that polymorphic variants in host genes, blood group and previous vaccination status against H1N1 may affect the clinical course of covid-19 infection. Method(s): A total of 202 subjects who were RT-PCR negative after Covid-19 infection were recruited. We investigated association between Covid-19 infection (Severity and recovery period) and multiple factors including ABO and Rh blood groups, H1N1 vaccination, polymorphism in Viral susceptibility genes (ACE2 G8790A), and polymorphism in host response genes (ACE I/D rs4646994, IL6- 174G/C, GSTT1/GSTM1 I/D and GSTP1 Ile 105 Val). Result(s): B-ve and O-ve ABO and Rh blood groups had significantly higher Covid-19 recovery period applied on one-vs.-all in a nonparametric t-test (p<0.05). Subjects who had vaccinated themselves against H1N1 presented with a lower recovery-period (p<0.05). Both variables (blood group and H1N1 vaccination) were not however associated with Covid-19 severity. Out of the studied polymorphisms, ACE2 G8790A and GSTT1/GSTM1 were significantly associated with covid-19 infection. Our results indicated that G/G genotype of ACE2 G8790A (OR 3.52, P 0.007) and GSTT1/ GSTM1 null (M1 - / - OR = 3.98, P = 0.0004;T1 - / - OR 3.84, P = 0.004) and double null (M1 - / - /T1 - / - OR = 9.66, P = 0.001) are likely to be associated with an increased risk for severe-critical outcomes in individuals with COVID-19. Other polymorphisms analyzed in this study were found to have no significant association with Covid-19 outcome. Conclusion(s): This study suggests that outcome of Covid-19 infection is affected by both clinical and genetic factors. Thus it seems plausible to utilize these factors as prediction and susceptibility markers in the prognosis of COVID-19, which may help to personalize the treatment.

THEMES AND CHALLENGES OF END OF LIFE CARE FOR COVID-19 PATIENTS REQUIRING NON-INVASIVE RESPIRATORY SUPPORT

Introduction The COVID-19 pandemic created new challenges due to the high numbers and the high symptom burden of end-of-life patients on respiratory support. Methods We conducted an audit of end-of-life patients on the respiratory HDU wards at Whipps Cross Hospital between 17/09/2020-30/01/2021. Results 84 patients receiving respiratory support (in the form of CPAP and HFNT) died during that time at a mean age of 77 (95% CI 67-87) and median of 79 years. All but one death, which followed a cardiac arrest, were expected. The most common clinical indicator for a patient approaching end-of-life was hypoxia on respiratory support, which was documented in 36 (43%) patients, followed by terminal agitation in 27 (32%) patients. Objections to the medical assessment of terminal illness were raised by 3 families and in 1 case the patient had conflicting wishes. The average time between recognition of a terminal deterioration and death was 1.4 days with a median of 2 days. 29 (35%) patients did not have a specialist palliative care review primarily due to the rapid patient deterioration. 25 (30%) patients were not visited by a relative due to the infection risk. 72 (86%) patients were weaned off respiratory support and those who continued did so due to a medical or patient decision. Despite most patients (82%) receiving continuous subcutaneous infusions with an opiate and benzodiazepine most patients had persistent terminal symptoms: 51 (74%) on infusions had agitation and 38 (55%) were persistently breathlessness. Discussion This data highlights some of the major difficulties faced in caring for patients with COVID on respiratory support and approaching end of life. With the inevitably persisting nature of this pandemic and the possibility of future pandemics still present, it is vital to be able to offer guidance and multidisciplinary input to ensure comfort and dignity for these patients.

Safety and effectiveness of the BNT162B2 mRNA COVID-19 vaccine in a nationwide cohort of patients with inflammatory bowel disease

BACKGROUND & AIMS: The effectiveness of currently available SARS-CoV-2 vaccines in patients with inflammatory bowel disease (IBD) remains unknown. We aimed to determine the effectiveness of the Pfizer-BNT162b2 mRNA vaccine in a nationwide cohort of patients with IBD in Qatar. METHODS: Using a cohort design, we compared 476 IBD patients vaccinated identified between January 1, 2021, and March 31, 2021, with 476 matched unvaccinated controls (matched on age and date of SARS-CoV-2 testing). Study outcomes included documented SARS-CoV-2 infection, symptomatic COVID-19, and COVID-19 related hospitalization. We also studied the side effects of the vaccination, including the effect on IBD exacerbation and hospitalizations related to adverse events. RESULTS: Total follow-up was 23,289 person-days for the vaccinated and 23,653 person-days for the unvaccinated group. Vaccine effectiveness >14 days [AAB1] after the second dose was 85.1% (95% CI: 65.2, 93.6) for confirmed infection, and 87.1% (95% CI: 63.6, 95.4)[AAB2] for symptomatic infection. No patient required hospitalization >14 days after the second vaccine dose. Estimated vaccine effectiveness between 22 to 35 days after the first dose was 14.8% (95% CI: -151.5, 71.2) [AAB3] for any documented infection, and 59.8% (95% CI: -106.1, 92.2) for symptomatic COVID-19 disease. For patients taking biologics with or without immunomodulators, vaccine effectiveness >14 days after the second dose was 94% (95% CI: 53.1, 99.2), and 92.7% (95% CI: 45.1, 99.0) for any documented infection and symptomatic COVID-19 respectively. Vaccine effectiveness was 87.4% (95% CI: 46.0, 97.1) for any documented infection and 91.7% (95% CI: 37.2, 98.9) for symptomatic COVID-19 during the same period for patients taking immunomodulators alone. None of the vaccinated patients required intensive care unit admission or died. No patient had IBD exacerbation or required hospitalization for vaccinationrelated adverse events. CONCLUSION: In a nationwide cohort of IBD patients, the BNT162b2 mRNA vaccine was safe and highly effective.

Challenges with end-of-life care in COVID patients requiring non-invasive respiratory support

IntroductionThe COVID-19 pandemic has seen an unprecedented number of adults receiving non-invasive respiratory support (NIRS) with such patients having a high mortality rate.MethodsAs part of better elucidating the challenges of end of life care delivery in the COVID era, we conducted an audit of our respiratory HDU ward at Whipps Cross Hospital focusing on a 19-week period between 17/09/2020–30/01/2021 and on patients who did not survive their admission. We excluded patients that were transferred to ITU.ResultsOf a total of 309 patients receiving NIRS on our ward, 84 died during that time at a mean age of 77 (95% CI 67–87) and median of 79 years. 63 patients received CPAP, 67 received HFNT and 42 were first started on HFNT and converted to CPAP. The average length of stay was 10 days (4–16). The mean day of symptoms on presentation to hospital was 11.5 days (1.7–21.3). Average duration of symptoms prior to admission to our ward was 19.7 (9.1–30.3) days.One death was unexpected and followed a cardiac arrest. The most common indicator for a patient approaching end-of-life was hypoxia on NIRS, which was documented in 36 (43%) patients, followed by terminal agitation in 27 (32%) patients. The average time between recognising end-of-life and death was 1.4 days with a median of 2 days. 72 (86%) patients were weaned off NIRS and those who continued did so due to a medical or patient decision. Despite the vast majority (82% of patients) being on syringe drivers with an opiate and benzodiazepine most patients had persistent terminal symptoms: 51 (74%) had agitation and 38 (55%) were persistently breathlessness. Interestingly, no patient opted to rest in the prone position.DiscussionThis data primarily suggests the challenging nature of managing end-of-life care for COVID patients deteriorating on NIRS due to the high symptom load and the short time there is to achieve comfort for these individuals. Clinicians need to conduct frequent comfort reviews for such patients, consider subcutaneous infusions, as well as potentially an increase in medication doses, in conjunction with specialist palliative care input, in order to achieve comfort.

Safety and feasibility of resuming bariatric surgery under the cloud of COVID-19.

INTRODUCTION: Because of the COVID-19 pandemic, numerous bariatric surgical units globally have halted weight loss surgery. Obesity itself has been shown to be a predictor of poor outcome in people infected with the virus. The aim of this study was to report our experience as a high-volume bariatric institution resuming elective weight loss surgery safely amidst emergency admissions of COVID-19-positive patients. METHODS: A standard operating procedure based on national guidance and altered to accommodate local considerations was initiated across the hospital. Data were collected prospectively for 50 consecutive patients undergoing bariatric surgery following recommencement of elective surgery after the first national lockdown in the UK. RESULTS: Between 28 June and 5 August 2020, a total of 50 patients underwent bariatric surgery of whom 94% were female. Median age was 41 years and median body mass index was 43.8 (interquartile range 40.0-48.8)kg/m2. Half of the patients (n = 25/50) underwent laparoscopic sleeve gastrectomy and half underwent Roux-en-Y gastric bypass (RYGB). Of these 50 patients, 9 (18%) had revisional bariatric surgery. Overall median length of hospital stay was 1 day, with 96% of the study population being discharged within 24h of surgery. The overall rate of readmission was 6% and one patient (2%) returned to theatre with an obstruction proximal to jejuno-jejunal anastomosis. None of the patients exhibited symptoms or tested positive for COVID-19. CONCLUSION: With appropriately implemented measures and precautions, resumption of bariatric surgery during the COVID-19 pandemic appears feasible and safe with no increased risk to patients.

Pregnancy with COVID-19: Weal and woe

Background: Coronavirus disease-2019 (COVID-19) has spread across the globe and has been declared pandemic by theWorld Health Organization (WHO). People of all age groups are at risk of getting the disease. Pregnant women are at an increased risk of acquiring the infection and developing moderate-to-severe pneumonia resulting in adverse outcome. Case Descriptions: Published case series have shown that high-risk pregnancies have been associated with higher morbidity and mortality. Pregnancy-induced immune response might have an impact on maternal cardiovascular system and exaggerate the course of COVID-19 disease. Here, we report two cases of late pregnancy with COVID-19 one of which ended with complete recovery and another with adverse outcome. Conclusion: These two case scenarios might add to the emerging evidence of pregnancy outcome in COVID-19. © The Author(s). 2020.