COVID-19 in solid organ transplant recipients: A single-center case series from Spain.

The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon-ß (16.7%). As of April 4, the case-fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C-reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.

Best practices during COVID-19 pandemic in solid organ transplant programs in Spain.

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.

Best practices during COVID-19 pandemic in solid organ transplant programs in Spain

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.

SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection.

Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein in noninfected subjects could inhibit, through the OAS mechanism, the response to new epitopes of SARS-CoV-2 after infection. The present study analyzes whether the memory antibody B cell response generated by mRNA vaccines against S protein can inhibit the primary antibody immune response to other SARS-CoV-2 antigens, such as nucleocapsid protein (N protein). SARS-CoV-2 primary infection in vaccinated healthcare workers (HCWs) produced significantly lower titers of anti-N antibodies than that in nonvaccinated HCWs: 5.7 (IQR 2.3-15.2) versus 12.2 (IQR 4.2-32.0), respectively (p = 0.005). Therefore, spike protein vaccine-induced immune imprinting (original antigenic sin) reduces N protein antibody response.

Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers.

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.

Real-Life Impact of Glucocorticoid Treatment in COVID-19 Mortality: A Multicenter Retrospective Study.

We aimed to determine the impact of steroid use in COVID-19 in-hospital mortality, in a retrospective cohort study of the SEMICOVID19 database of admitted patients with SARS-CoV-2 laboratory-confirmed pneumonia from 131 Spanish hospitals. Patients treated with corticosteroids were compared to patients not treated with corticosteroids; and adjusted using a propensity-score for steroid treatment. From March-July 2020, 5.262 (35.26%) were treated with corticosteroids and 9.659 (64.73%) were not. In-hospital mortality overall was 20.50%; it was higher in patients treated with corticosteroids than in controls (28.5% versus 16.2%, OR 2.068 [95% confidence interval; 1.908 to 2.242]; p = 0.0001); however, when adjusting by occurrence of ARDS, mortality was significantly lower in the steroid group (43.4% versus 57.6%; OR 0.564 [95% confidence interval; 0.503 to 0.633]; p = 0.0001). Moreover, the greater the respiratory failure, the greater the impact on mortality of the steroid treatment. When adjusting these results including the propensity score as a covariate, in-hospital mortality remained significantly lower in the steroid group (OR 0.774 [0.660 to 0.907], p = 0.002). Steroid treatment reduced mortality by 24% relative to no steroid treatment (RRR 0.24). These results support the use of glucocorticoids in COVID-19 in this subgroup of patients.

Effect of Coronavirus Disease 2019 in Pulmonary Circulation. The Particular Scenario of Precapillary Pulmonary Hypertension.

The Coronavirus Disease of 2019 (COVID-19) has supposed a global health emergency affecting millions of people, with particular severity in the elderly and patients with previous comorbidities, especially those with cardiovascular disease. Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) could represent an especially vulnerable population because of the high mortality rates reported for respiratory infections. However, the number of COVID-19 cases reported among PAH and CTEPH patients is surprisingly low. Furthermore, the clinical picture that has been described in these patients is far from the severity that experts would expect. Endothelial dysfunction is a common feature between patients with PAH/CTEPH and COVID-19, leading to ventilation/perfusion mismatch, vasoconstriction, thrombosis and inflammation. In this picture, the angiotensin-converting enzyme 2 plays an essential role, being directly involved in the pathophysiology of both clinical entities. Some of these common characteristics could explain the good adaptation of PAH and CTEPH patients to COVID-19, who could also have obtained a benefit from the disease's specific treatments (anticoagulant and pulmonary vasodilators), probably due to its protective effect on the endothelium. Additionally, these common features could also lead to PAH/CTEPH as a potential sequelae of COVID-19. Throughout this comprehensive review, we describe the similarities and differences between both conditions and the possible pathophysiological and therapeutic-based mechanisms leading to the low incidence and severity of COVID-19 reported in PAH/CTEPH patients to date. Nevertheless, international registries should look carefully into this population for better understanding and management.