"Salus Populi Suprema Lex": Considerations on the Initial Response of the United Kingdom to the SARS-CoV-2 Pandemic.

In several countries worldwide, the initial response to coronavirus disease 2019 (COVID-19) has been heavily criticized by general public, media, and healthcare professionals, as well as being an acrimonious topic in the political debate. The present article elaborates on some aspects of the United Kingdom (UK) primary reaction to SARS-CoV-2 pandemic; specifically, from February to July 2020. The fact that the UK showed the highest mortality rate in Western Europe following the first wave of COVID-19 certainly has many contributing causes; each deserves an accurate analysis. We focused on three specific points that have been insofar not fully discussed in the UK and not very well known outside the British border: clinical governance, access to hospital care or intensive care unit, and implementation of non-pharmaceutical interventions. The considerations herein presented on these fundamental matters will likely contribute to a wider and positive discussion on public health, in the context of an unprecedented crisis.

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.

The Management of Immunosuppression in Kidney Transplant Recipients with COVID-19 Disease: An Update and Systematic Review of the Literature.

Background and Objectives: In the era of the coronavirus disease 2019 (COVID-19) pandemic, the management of immunosuppressive (IS) therapy in kidney transplant (KT) recipients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires attention. It is not yet understood whether IS therapy may protect from the cytokine storm induced by SARS-CoV-2 infection or a temporary adjustment/withdrawal of IS therapy to restore the immune system may be necessary. We performed a systematic literature review to investigate the current management of IS therapy in KT recipients with COVID-1. Materials and Methods: Out of 71 articles published from 1 February 2020 until 30 October 2020, 554 KT recipients with SARS-CoV-2 infection were identified. Results: Modifications of IS therapy were based on the clinical conditions. For asymptomatic patients or those with mild COVID-19 symptoms, a "wait and see approach" was mostly used; a suspension of antimetabolites drugs (347/461, 75.27%) or mTOR inhibitors (38/48, 79.2%) was adopted in the majority of patients with symptomatic COVID-19 infections. For CNIs, the most frequent attitude was their maintenance (243/502, 48.4%) or dose-reduction (99/502, 19.72%) in patients asymptomatic or with mild COVID-19 symptoms, while drug withdrawal was the preferred choice in severely symptomatic patients (160/450, 31.87%). A discontinuation of all IS drugs was used only in severely symptomatic COVID-19 patients on invasive mechanical ventilation. Renal function remained stable in 422(76.17%) recipients, while 49(8.84%) patients experienced graft loss. Eight (1.44%) patients experienced a worsening of renal function. The overall mortality was 21.84%, and 53(9.56%) patients died with functioning grafts. Conclusion: A tailored approach to the patient has been the preferred strategy for the management of IS therapy in KT recipients, taking into account the clinical conditions of patients and the potential interactions between IS and antiviral drugs, in the attempt to balance the risks of COVID-19-related complications and those due to rejection or graft loss.

Liver transplantation performed in a SARS-CoV-2 positive hospitalized recipient using a SARS-CoV-2 infected donor.

The coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 currently affected more than 108 million people worldwide with a fatality rate of 2.2%. Herein, we report the first case of liver transplantation (LT) performed with a liver procured from a SARS-CoV-2 positive donor. The recipient was a 35-year-old SARS-CoV-2 positive female patient affected by severe end-stage HBV-HDV-related liver disease (model of end-stage liver disease = 32) who had neutralizing SARS-CoV-2 antibodies (titers 1:320) at time of LT. The LT was successful, and the graft is functioning two months after surgery. The recipient cleared the SARS-CoV-2 infection 1 month after LT. The current case shows that the prompt use of SARS-CoV-2 infected liver donors offers an invaluable life-saving opportunity for SARS-CoV-2 positive wait-listed patients who developed neutralizing SARS-CoV-2 antibodies.

Awareness and Impact of Non-pharmaceutical Interventions During Coronavirus Disease 2019 Pandemic in Renal Transplant Recipients.

The concerns generated by coronavirus disease 2019 (COVID-19) pandemic are having profound impact on solid organ transplantation (SOT). Non-pharmaceutical interventions (NPI) are currently the only measures available to contain COVID-19 in the general population and in more vulnerable recipients of any organ transplant. In this cross-sectional case control study from a patient survey undertaken in 2 transplant centers (TxC) in the Kingdom of Saudi Arabia and Italy, we aimed to appraise awareness of the NPI implemented by respective these governments. We have also evaluated the impact of COVID-19 on our kidney transplant (KT) recipients and a control group of kidney living donors (KLD). In our series, there were zero cases of COVID-19 among 111 KT recipients and 70 KLD of the control group. Demography, transplant type, immunosuppression regimes, and, importantly, the different COVID-19 prevalence in the 2 regions of the TxC did not appear to influence incidence of COVID-19 in our KT recipients. The absence of COVID-19 cases in our series was unexpected. Our findings suggest that awareness of NPI is associated with a successful containment of COVID-19 in vulnerable, immunosuppressed KT recipients.

Global management of a common, underrated surgical task during the COVID-19 pandemic: Gallstone disease - An international survery.

BACKGROUND: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. METHODS: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. RESULTS: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50-75%, 10(27.8%) by 25-50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months.In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. CONCLUSION: In the ongoing COVID-19 emergency, the surgical treatment of GD is postponed, resulting in a huge number of untreated patients who could develop severe morbidity. Updated guidelines and dedicated pathways for patients with benign disease awaiting elective surgery are mandatory to prevent further aggravation of the overloaded healthcare systems.

COVID-19, liver transplant, and immunosuppression: Allies or foes?

Liver transplant (LT) recipients are considered at a particularly high risk for developing critical COVID-19 infection. To date, available data are heterogeneous and scarce and mortality in LT recipients seems to be higher compared to normal population, but whether this is caused by altered immunological status, immunosuppression (IS), or underlying comorbidities has not yet been fully clarified. Some evidences show that IS might play a role in the pathophysiology of this new disease. We searched all available data regarding LT recipients infected by COVID-19, focusing on the role of IS. To date, 244 LT recipients have been reported as COVID-19-positive. Trends among transplant physicians are to reduce overall IS, especially antimetabolite drugs, but the current available observations are still not enough to build strong evidences for recommendation and IS should be meticulously tailored case by case.

The COVID-19 outbreak in Italy: Initial implications for organ transplantation programs.

The spread of Coronavirus Disease 2019 (COVID-19) has already reached a pandemic dimension within a few weeks. Italy has been one of the first countries dealing with the outbreak of COVID-19, and severe measures have been adopted to limit viral transmission. The spread of COVID-19 may have several implications in organ transplant activity that physicians should be aware of. The initial experience gained during the COVID-19 outbreak shows that around 10% of infected patients in Italy need intensive care management to overcome the acute respiratory distress syndrome. Due to the exponential rise of infected patients we are now facing an actual risk of saturation of intensive care unit (ICU) beds. A restriction in the number of ICU beds available for both donors and transplant recipients may unfavorably influence the overall donation activity, and eventually lead to a reduced number of transplants. Preliminary Italian data show that a 25% reduction of procured organs has already occurred during the first 4 weeks of COVID-19 outbreak. This underlines the need to closely monitor what will be further happening in ICUs due to the COVID-19 spread in the attempt to preserve transplant activity, especially in Western countries where deceased donors represent the major organ resource.