BOOST KIDNEY: A Randomized Controlled Trial of Third Dose BNT162b2 vs. mRNA-1273 COVID-19 Vaccination in CKD and Dialysis Patients

Background: Due to waning humoral immunity, a third COVID-19 vaccine dose is recommended but there is a lack of evidence regarding whether there is benefit to homologous versus heterologous mRNA vaccination. Method(s): This was a multi-centre parallel group randomized controlled trial in Toronto, Ontario from September 30, 2021 to May 13, 2022 which enrolled participants with stage 3B-5 chronic kidney disease with prior homologous mRNA two dose vaccination. Overall 273 participants were randomized 1:1 to either 30mug BNT162b2 (n=137) or 100 mug mRNA-1273 (n=136) third dose stratified by initial vaccine type. Neutralizing antibodies against the B.1.1.529 (Omicron) variant of concern as well as binding SARS-CoV-2 IgG antibodies to the spike protein, receptor binding domain, and nucleocapsid protein were measured. Result(s): Participants had a median age of 67 years, 94% were on dialysis, 3% had prior COVID-19, and 59% had received BNT162b2 for initial two dose vaccination. Prior to the third vaccine dose, detectable Omicron neutralizing antibodies were present in 2% with BNT162b2 and 54% with mRNA-1273 two dose vaccination. At 1 month post third dose, among those with baseline BNT162b2, Omicron-specific neutralizing antibodies were detectable in 84% with third dose BNT162b2 in comparison to 83% with third dose mRNA-1273 (p=0.70). In those with baseline mRNA-1273, 100% receiving third dose mRNA-1273 had Omicron-specific neutralizing antibodies in comparison to 96% with third dose BNT162b2 (p=0.75). During the study period, 9.3% of participants (n=25) contracted COVID-19 and two died from COVID-19 with no difference in infection based on vaccine type (p=0.26). Conclusion(s): In this randomized controlled trial of third dose COVID-19 vaccination, both homologous and heterologous vaccination elicited robust SARS-CoV-2 neutralizing antibody response. (Figure Presented).

Long-Term Effect of COVID-19 Infection on Kidney Function Among COVID-19 Patients Followed in a Post-COVID-19 Recovery Clinic in British Columbia, Canada

Background: Recent research suggests that COVID-19 is associated with acute kidney dysfunction. Effect of COVID-19 infection on downstream kidney function is unknown. We investigated this using the BC Interdisciplinary COVID-19 Care Network data. Method(s): This retrospective cohort study analyzed a 2,212 COVID-19 patient cohort, aged >=18 years, referred to the Post COVID Recovery Clinic (PCRC) in BC, Canada between July 9, 2020 & April 21, 2022. COVID-19 diagnosis date was the index date. Patients with history of kidney transplantation or dialysis before index date were excluded. Patients who deceased within 3 months of cohort entry were excluded. eGFR values were retrieved from the Provincial Laboratory Information System. We examined change in eGFR at 3-, 6-, 12-months after COVID-19 infection among the same study individuals using linear mixed model. Subgroup analysis included comparison between hospitalized vs. non-hospitalized, & diabetics vs. non-diabetics. Result(s): Analytic cohort included 457 patients (median age 59 years, 50% male) for whom eGFR was recorded at 3-, 6-, 12-months from index date. Prevalence of reduced eGFR (<=59ml/min/1.73m2) was 16%, 16%, 17% at 3-, 6-and 12-months post-index date, respectively. Median (IQR) eGFR at baseline was 90 (73, 102) that was reduced to 85 (70, 101) at 6-months & remained stable or <previous value at 12 months postindex date, 86 (69, 101). Results from linear mixed model indicated a 0.23 ml/min decrease in eGFR in each month after COVID-19 infection (intercept 85.51, slope -0.23, p-value=0.0003). In subgroup analyses, similar trends of decreasing eGFR over time were observed among diabetic (n=188, intercept 83.08, slope -0.42, p-value=0.0001) & nondiabetic patients (n=269, intercept 87.33, slope -0.12, p-value=0.13). Interestingly, eGFR appeared to improve over time in non-hospitalized patients (n=133, intercept 88.34, slope 0.24, p-value=0.03) compared to a decreasing trend among hospitalized patients (n=324, intercept 83.94, slope -0.41, p-value=<0.001). Conclusion(s): One in 6 COVID-19 patients who were referred to PCRC had reduced eGFR. COVID-19 was associated with a statistically significant decrease in eGFR, particularly in diabetic & hospitalized patients that warrants ongoing monitoring following COVID-19 infection.

Humoral Responses in the Omicron Era Following a Three-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients

Background: Kidney transplant recipients (KTR) have a diminished response to SARS-CoV-2 vaccination in comparison to immunocompetent individuals. Deeper understanding of the antibody response in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron and require additional treatment strategies. Method(s): We profiled antibody responses in KTRs pre-and at one and three months post-third-dose SARS-CoV2 mRNA-based vaccine. Anti-spike and anti-RBD IgG levels were determined by ELISA. Neutralization against wild-type, Beta, Delta and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay. Result(s): 44 KTRs were analysed at 1 and 3 months (n=26) post-third-dose. At one month, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median anti-spike and anti-RBD antibody levels declined at 3 months, but the proportion of KTRs with a robust antibody response was unchanged. 38.5% KTRs maintained Omicron-specific neutralization at 3 months. No clinical variables were significantly associated with detectable Omicron neutralizing antibodies, but anti-RBD titres appeared to identify those with Omicron-specific neutralizing capacity. Conclusion(s): Over 50% of KTRs lack an Omicron-specific neutralization response 1 month following a third mRNA-vaccine dose. Among responders, binding and neutralizing antibody responses were well preserved at 3 months. Anti-RBD antibody titres may be a useful identifier of patients with detectable Omicron neutralizing antibody response.

Is COVID-19 Infection Associated With the Progression of Kidney Disease? Findings From a Population Based Observational Study From British Columbia, Canada

Background: Recent research suggests that COVID-19 infection is associated with acute kidney injury (AKI). Together the inflammation caused by the virus in the kidneys and the episodes of AKIs are risk factors for progression of kidney diseases. We investigated the risk of progression to kidney failure among chronic kidney disease (CKD) patients from BC, Canada who were infected with COVID-19. Method(s): In this retrospective cohort study, we analyzed a cohort of 22,188 nondialysis CKD patients aged >=18 years, with no prior history of ESKD and COVID-19 infection before the cohort entry date between January 27, 2020 & December 15, 2021. The cohort was derived from Patient Records and Outcome Management Information System (PROMIS), a population based integrated registry database for CKD patients under the nephrologist care in BC. Incident COVID-19 cases were iteratively matched without replacement to non-COVID-19 controls (1:3 ratio) based on age, sex, region of residency, diabetes status, eGFR and urine ACR, CKD vintage and COVID-19 vaccination status as of COVID-19 diagnosis date. The primary outcome was a composite of initiation of maintenance dialysis defined by dialysis performed for >=4 weeks, a sustained decline in eGFR defined by >=40% decline from baseline that sustained over >=4 weeks or incident kidney transplantation. Estimated HR and 95% CI using Fine and Gray subdistribution hazard model to account for death as a competing risk. Result(s): The analytic data included 1,708 patients, 475 (28%) COVID-19 cases and 1,233 (72%) non-COVID-19 controls. Median age was 71 years, 53% was male. Median follow-up was 8.3 months, 70 (4.10%) patients progressed to kidney failure. Among the non-dialysis CKD patients, the risk of developing kidney failure in COVID-19 infected cases was 24% higher compared to matched, non-COVID-19 infected controls. The HR (95% CI) was 1.24 (0.75, 2.06) (p-value: 0.39). Conclusion(s): COVID-19 infection in non-dialysis CKD patients appeared to be associated with higher risk of progression to kidney failure. Although not statistically significant, the substantial increase in risk estimate warrants close monitoring of kidney function among CKD patients after COVID-19 infection.

Healthcare-associated infections: a threat to the survival of patients with COVID-19 in intensive care units.

BACKGROUND: Wide variation in mortality rates among critically ill patients with coronavirus disease 2019 (COVID-19) has been reported. This study evaluated whether healthcare-associated infections (HAI) are a risk factor for death among patients with severe COVID-19 in the intensive care unit (ICU). METHODS: This retrospective cohort study included patients with severe COVID-19 hospitalized in the ICU of four hospitals in the city of Curitiba, Brazil. Patients with COVID-19 who died during ICU hospitalization were compared with those who were discharged. A second analysis compared patients who developed HAI in the ICU with those who did not. Multiple logistic regression models were used to control for confounders. RESULTS: In total, 400 patients were included, and 123 (31%) patients developed HAI. The most common HAI was lower respiratory tract infection (67%). Independent risk factors for death were: age [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.43-2.15; P<0.0001]; clinical severity score (OR 2.21, 95% CI 1.70-2.87; P<0.0001); renal replacement therapy (OR 12.8, 95% CI 5.78-28.6; P<0.0001); and HAI (OR 5.9, 95% CI 3.31-10.5; P<0.0001). A longer interval between symptom onset and hospital admission was protective against death (OR 0.93, 95% CI 0.88-0.98; P=0.017). The only independent factors associated with HAI were high C-reactive protein and low PaO2/FiO2 ratio. CONCLUSIONS: No factors that could point to a high-risk group for HAI acquisition were identified. However, age, dialysis and HAI increased the risk of death in ICU patients with severe COVID-19; of these, HAI is the only preventable risk factor.

Nationwide surveillance system to evaluate hospital-acquired COVID-19 in Brazilian hospitals.

BACKGROUND: Although the risk of SARS-CoV-2 transmission within hospitals has been well recognized, there is a paucity of data on its occurrence. Our aim was to report the incidence of hospital-acquired (HA) COVID-19 at Brazilian hospitals. METHODS: We investigated the incidence of HA COVID-19 in Brazilian hospitals using data from a national surveillance system, from August 2020 through September 2021. Definitions of HA COVID-19 were: (1) symptom onset >14 days after hospital admission plus a positive SARS-CoV-2 RNA or antigen test; (2) symptom onset on days 8-14 after admission, plus a positive SARS-CoV-2 RNA or antigen test positive, plus documented high-risk exposure. We performed descriptive analyses and reported HA COVID-19 rates using pooled mean and percentile distribution. RESULTS: A total of 48,634 cases of HA COVID-19 were reported from 1428 hospitals. Incidence ranged from 0.16/1000 patient-days at neonatal intensive care units (ICUs) to 5.8/1000 patient-days at adult ICUs. The highest incidence of HA COVID-19 was during the months March to July 2021, similar to that which was observed for community-acquired COVID-19. CONCLUSIONS: This report provides a national view of the burden of HA COVID-19. The highest incidence of HA COVID-19 similar that which was observed for community-acquired COVID-19. We believe that this reflects the difficulty of implementing preventive measures. Further studies evaluating risk factors for the hospital transmission of SARS-Cov-2 should clarify strategies to minimize the risk of HA COVID-19 and may be applicable to other respiratory diseases. Furthermore, the implementation of a national system to evaluate HA COVID-19 has the potential to shine a light on this problem and lead to interventions in each hospital.

Acute Kidney Injury and Renal Replacement Therapy in COVID-19 Versus Other Respiratory Viruses: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute kidney injury (AKI) is a potentially fatal complication of Coronavirus Disease-2019 (COVID-19). Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, to its viral receptor, angiotensin converting enzyme 2 (ACE2), results in viral entry and may cause AKI. OBJECTIVES: We performed a systematic review and meta-analysis of the frequencies of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients and compared those frequencies with patients who were infected by respiratory viruses that bind or downregulate ACE2 (ACE2-associated viruses) and viruses that do not bind nor downregulate ACE2 (non-ACE2-associated viruses). DESIGN: Systematic review and meta-analysis. SETTING: Observational studies on COVID-19 and other respiratory viral infections reporting AKI and RRT were included. The exclusion criteria were non-English articles, non-peer-reviewed articles, review articles, studies that included patients under the age of 18, studies including fewer than 10 patients, and studies not reporting AKI and RRT rates. PATIENTS: Adult COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and influenza patients. MEASUREMENTS: We extracted the following data from the included studies: author, year, study location, age, sex, race, diabetes mellitus, hypertension, chronic kidney disease, shock, vasopressor use, mortality, intensive care unit (ICU) admission, ICU mortality, AKI, and RRT. METHODS: We systematically searched PubMed and EMBASE for articles reporting AKI or RRT. AKI was defined by authors of included studies. Critical illness was defined by ICU admission. We performed a random effects meta-analysis to calculate pooled estimates for the AKI and RRT rate within each virus group using a random intercept logistic regression model. RESULTS: Of 23 655 hospitalized, critically ill COVID-19 patients, AKI frequencies were not significantly different between COVID-19 patients (51%, 95% confidence interval [CI]: 44%-57%) and critically ill patients infected with ACE2-associated (56%, 95% CI: 37%-74%, P = .610) or non-ACE2-associated viruses (63%, 95% CI: 43%-79%, P = .255). Pooled RRT rates were also not significantly different between critically ill, hospitalized patients with COVID-19 (20%, 95% CI: 16%-24%) and ACE2-associated viruses (18%, 95% CI: 8%-33%, P = .747). RRT rates for both COVID-19 and ACE2-associated viruses were significantly different (P < .001 for both) from non-ACE2-associated viruses (49%, 95% CI: 44%-54%). After adjusting for shock or vasopressor use, AKI and RRT rates were not significantly different between groups. LIMITATIONS: Limitations of this study include the heterogeneity of definitions of AKI that were used across different virus studies. We could not match severity of infection or do propensity matching across studies. Most of the included studies were conducted in retrospective fashion. Last, we did not include non-English publications. CONCLUSIONS: Our findings suggest that viral ACE2 association does not significantly alter the rates of AKI and RRT among critically ill patients admitted to the ICU. However, the rate of RRT is lower in patients with COVID-19 or ACE2-associated viruses when compared with patients infected with non-ACE2-binding viruses, which might partly be due to the lower frequencies of shock and use of vasopressors in these two virus groups. Prospective studies are necessary to demonstrate whether modulation of the ACE2 axis with Renin-Angiotensin System inhibitors impacts the rates of AKI and whether they are beneficial or harmful in COVID-19 patients.

MISE EN CONTEXTE: L'insuffisance rénale aiguë (IRA) est une complication potentiellement mortelle de la maladie à coronavirus-2019 (COVID-19). Obligatoire du Coronavirus 2 du Syndrome Respiratoire Aigu Sévère (SARS-CoV-2), le virus responsable du COVID-19, à son récepteur, l'enzyme de conversion de l'angiotensine 2 (ACE2), entraîne une entrée virale et peut provoquer une IRA. OBJECTIFS DE L'ÉTUDE: Nous avons effectué une revue systématique et une méta-analyse des fréquences de l'IRA et de la thérapie de remplacement renal (RRT) chez les patients COVID-19 gravement malades et a comparé ces fréquences avec les patients qui ont été infectés par des voies respiratoires virus qui lient ou régulent négativement l'ACE2 (virus associés à l'ACE2) et les virus qui ne régulent pas négativement ni ne lient l'ACE2 (virus non associés à l'ACE2). CADRE ET TYPE D'ÉTUDE: Revue systématique et méta-analyse. Des études d'observation sur le COVID-19 et d'autres infections virales respiratoires signalant une AKI et une RRT ont été incluses. Les critères d'exclusion étaient des articles non anglophones, des articles non évalués par des pairs, des articles de revue, des études incluant des patients moins de 18 ans, les études incluant moins de 10 patients et les études ne rapportant pas les taux d'IRA et de RRT. PATIENTS: Adultes COVID-19, syndrome respiratoire aigu sévère (SRAS), syndrome respiratoire du Moyen-Orient (MERS) et malades de la grippe. MESURES: Nous avons extrait les données suivantes des études incluses : auteur, année, lieu de l'étude, âge, sexe, race, diabète sucré, hypertension, maladie rénale chronique, état de choc, utilisation de vasopresseurs, mortalité, admission en unité de soins intensifs (USI), Mortalité en soins intensifs, AKI et RRT. MÉTHODOLOGIE: Nous avons systématiquement recherché dans PubMed et EMBASE les articles rapportant AKI ou RRT. AKI a été défini par les auteurs des études incluses. La maladie grave a été définie par l'admission aux soins intensifs. Nous avons effectué une méta-analyse à effets aléatoires pour calculer estimations regroupées pour le taux d'IRA et de RRT au sein de chaque groupe de virus à l'aide d'un modèle de régression logistique d'interception aléatoire. RÉSULTATS: Sur 23 655 patients hospitalisés et gravement malades COVID-19, les fréquences AKI n'étaient pas significativement différentes entre patients COVID-19 (51 %, intervalle de confiance à 95 % [IC] : 44 %-57 %) et patients gravement malades infectés par l'ACE2 associé (56 %, IC à 95 % : 37 % à 74 %, P = 0,610) ou des virus non associés à l'ACE2 (63 %, IC à 95 % : 43 % à 79 %, P = 0,255). Tarifs RRT groupés n'étaient pas non plus significativement différents entre les patients hospitalisés gravement malades atteints de COVID-19 (20 %, IC à 95 % : 16 % à 24 %) et virus associés à l'ACE2 (18 %, IC à 95 % : 8 % à 33 %, P = 0,747). Taux de RRT pour les virus associés au COVID-19 et à l'ACE2 étaient significativement différents (P < 0,001 pour les deux) des virus non associés à l'ACE2 (49 %, IC à 95 % : 44 % à 54 %). Après ajustement pour le choc ou l'utilisation de vasopresseurs, les taux d'IRA et de RRT n'étaient pas significativement différents entre les groupes. LIMITES DE L'ÉTUDE: Les limites de cette étude incluent l'hétérogénéité des définitions de l'IRA qui ont été utilisées pour différents virus études. Nous n'avons pas pu faire correspondre la gravité de l'infection ou faire une correspondance de propension entre les études. La plupart des études incluses ont été menées de manière rétrospective. Enfin, nous n'avons pas inclus les publications non anglophones. CONCLUSIONS: Nos résultats suggèrent que l'association virale ACE2 ne modifie pas de manière significative les taux d'IRA et de RRT parmi les patients gravement malades admis aux soins intensifs. Cependant, le taux de RRT est plus faible chez les patients atteints de COVID-19 ou associés à l'ACE2 virus par rapport aux patients infectés par des virus ne se liant pas à l'ACE2, ce qui pourrait être dû en partie à la plus faible fréquences de choc et utilisation de vasopresseurs dans ces deux groupes de virus. Des études prospectives sont nécessaires pour démontrer si la modulation de l'axe ACE2 avec les inhibiteurs du système rénine-angiotensine a un impact sur les taux d'IRA et si ells sont bénéfiques ou nocifs chez les patients COVID-19.

Outcomes by race for cancer patientshospitalized with SARS-CoV-2 infection

Purpose: Disparities in COVID-19 outcomes have been widely reported, with disproportionate negative impacts onthe African American (AA) population. The purpose of this study was to evaluate the impact of race on COVID-19outcomes for cancer patients hospitalized in a large Michigan health care system. Methods: A cohort of hospitalized, laboratory-confirmed SARS-CoV-2 positive patients was identified through theHenry Ford Health System Institutional COVID prospective patient registry between March 1st-May 2020. Those with a diagnosis of cancer were identified using our institutional tumor registry and electronic health record (EHR).Patient self-reported race/ethnicity data were extracted from the system's centralized EHR, as were otherdemographic and clinical covariates. Racial differences in cumulative incidence of mortality and hospital discharge were tested. To further evaluate the effect of race on the mortality, Fine-Gray competing-risks model was performed with discharge alive as a competing event. A P<0.05 was considered statistically significant. Results: Out of the 204 COVID+ cancer patients hospitalized in our health care system, 69.6% were AA (N=142).AA patients were slightly younger than non-AA patients (70.35 v. 74.58, p=0.023). No difference in mean BMI wasdetected (30.33 AA v. 29.87 non-AA, p = 0.68). A smaller proportion of AA patients had active cancer (36.6% v.40.3%, p = 0.73). Outcomes were generally inferior in the AA cohort, although these differences were notstatistically significant. The rate of ICU admission was 41.5% in AA and 37.1% in non-AA (p=0.659). 34.5% of AApatients required intubation compared to 25.8% of non-AA patients (p=0.288). In our model, older age was the onlyvariable that significantly increased the risk of death (standard hazard ratio SHR 1.05, p = 0.002). The risk of death was higher for AA patients (SHR 1.92, p=0.068) and males (SHR 1.62, p = 0.078) but did not meet statisticalsignificance.