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1.
Nat Commun ; 12(1): 1891, 2021 03 25.
Article in English | MEDLINE | ID: covidwho-1387333

ABSTRACT

Monoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/therapeutic use , Marburg Virus Disease/drug therapy , Marburgvirus/drug effects , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Animals , Disease Models, Animal , Drug Therapy, Combination , Macaca mulatta , Marburg Virus Disease/prevention & control , Viral Load/drug effects
2.
Hepatology ; 74(2): 1049-1064, 2021 08.
Article in English | MEDLINE | ID: covidwho-1372725

ABSTRACT

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.


Subject(s)
COVID-19 Vaccines/standards , COVID-19/prevention & control , Liver Diseases , Liver Transplantation , Adult , COVID-19 Vaccines/administration & dosage , Consensus , Humans , Practice Guidelines as Topic , SARS-CoV-2/immunology , United States
3.
Curr Oncol ; 28(2): 1338-1347, 2021 03 24.
Article in English | MEDLINE | ID: covidwho-1348609

ABSTRACT

Practice and behaviour change in healthcare is complex, and requires a set of critical steps that would be needed to implement and sustain the change. Neoadjuvant chemotherapy for breast cancer is traditionally used for locally advanced disease and is primarily advantageous for surgical downstaging purposes. However, it does also offer patients with certain biologic subtypes such as the triple negative or Her2 positive breast cancers the opportunity to improve survival, even in early stage disease. During the height of the pandemic, an opportunity and motivation for the increased use of neoadjuvant therapy in breast cancer was identified. This paper describes the conditions that have supported this practice change at the provider and institutional levels. We also include our own institutional algorithm based on tumor biology and extent of disease that have guided our decisions on breast cancer management during the pandemic. Our processes can be adapted by other institutions and breast oncology practices in accordance with local conditions and resources, during and beyond the pandemic.


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Female , Humans , Pandemics , Receptor, ErbB-2
4.
Internist (Berl) ; 62(7): 718-724, 2021 Jul.
Article in German | MEDLINE | ID: covidwho-1326807

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has also resulted in substantial challenges for nephrology worldwide. Patients with chronic kidney diseases are a particularly vulnerable patient group in this context and in severe courses of COVID-19 the kidneys are most frequently affected by organ failure after the lungs. MATERIAL AND METHODS: In order to reliably evaluate the prevalence and mortality of dialysis patients in Germany with respect to COVID-19, during the first wave in spring 2020 the German Society of Nephrology implemented a registry for dialysis patients. Weekly data on the number and course of dialysis patients affected by COVID-19 were recorded and analyzed. RESULTS: The prevalence of COVID-19 in dialysis patients in Germany developed in two waves, similar to the course of the pandemic in the general population. In spring the prevalence in dialysis patients reached 1.4% and considerably declined during the summer. In December during the second wave of the pandemic the prevalence again rose to 1.9%, despite comprehensively implemented hygiene measures in dialysis centers. Similar to other industrial nations, dialysis patients in Germany also showed a very high lethality of COVID-19 of up to 20%. CONCLUSION: Immediate consequences for hygiene measures in dialysis institutions as well as vaccination strategies and vaccination prioritization for this patient group and the personnel treating them can be derived from the high mortality in dialysis patients. A consequence of the frequent involvement of the kidneys during infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients who had not previously suffered from advanced kidney disease should be the consistent nephrological aftercare.


Subject(s)
COVID-19 , Nephrology , Germany/epidemiology , Humans , Pandemics/prevention & control , Renal Dialysis , SARS-CoV-2
5.
Nat Rev Gastroenterol Hepatol ; 18(5): 348-364, 2021 05.
Article in English | MEDLINE | ID: covidwho-1127158

ABSTRACT

Our understanding of the hepatic consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resultant coronavirus disease 2019 (COVID-19) has evolved rapidly since the onset of the pandemic. In this Review, we discuss the hepatotropism of SARS-CoV-2, including the differential expression of viral receptors on liver cell types, and we describe the liver histology features present in patients with COVID-19. We also provide an overview of the pattern and relevance of abnormal liver biochemistry during COVID-19 and present the possible underlying direct and indirect mechanisms for liver injury. Furthermore, large international cohorts have been able to characterize the disease course of COVID-19 in patients with pre-existing chronic liver disease. Patients with cirrhosis have particularly high rates of hepatic decompensation and death following SARS-CoV-2 infection and we outline hypotheses to explain these findings, including the possible role of cirrhosis-associated immune dysfunction. This finding contrasts with outcome data in pharmacologically immunosuppressed patients after liver transplantation who seem to have comparatively better outcomes from COVID-19 than those with advanced liver disease. Finally, we discuss the approach to SARS-CoV-2 vaccination in patients with cirrhosis and after liver transplantation and predict how changes in social behaviours and clinical care pathways during the pandemic might lead to increased liver disease incidence and severity.


Subject(s)
COVID-19/epidemiology , Liver Diseases/epidemiology , Pandemics , Comorbidity , Disease Progression , Humans , SARS-CoV-2
6.
J Immunother Cancer ; 9(2)2021 02.
Article in English | MEDLINE | ID: covidwho-1088281

ABSTRACT

BACKGROUND: In ambulatory patients with cancer with asymptomatic or pauci-symptomatic SARS-CoV-2 infection, the safety of targeted therapies (TTs), chemotherapy (CT) or immune checkpoint inhibitors (ICIs) therapy is still unknown. MATERIAL AND METHODS: From the start of the first epidemic wave of SARS-CoV-2 in Bergamo, Italy, we have prospectively screened all consecutive outpatients who presented for treatment to the Oncology Division of the Papa Giovanni XXIII Hospital, Bergamo for SARS-CoV-2 antigen expression. We identified patients treated with ICIs and compared these to patients with the same cancer subtypes treated with TTs or CT. RESULTS: Between March 5 and May 18, 293 consecutive patients (49% melanoma, 34% non-small cell lung cancer, 9% renal cell carcinoma, 8% other) were included in this study: 159 (54%), 50 (17%) and 84 (29%) received ICIs, CT or TTs, respectively. Overall 89 patients (30.0%) were SARS-CoV-2 positive. Mortality of SARS-CoV-2-positive patients was statistically significantly higher compared with SARS-CoV-2 negative patients (8/89 vs 3/204, respectively, Fisher's exact test p=0.004). All deaths were due to COVID-19. Serious adverse events (SAEs) were more frequent in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative cases (Cochran-Mantel-Haenszel (CMH) test p=0.0008). The incidence of SAEs in SARS-CoV-2 positive compared with SARS-CoV-2 negative patients was similar in ICI and CT patients (17.3% and 3.7% for positive and negative patients in ICIs and 15.4% and 2.7% in CT, Breslow-Day test p=0.891). No COVID-19-related SAEs were observed in the TTs patients. CONCLUSIONS: The incidence of SAEs was higher for SARS-CoV-2-positive patients treated with ICIs and CT, mostly in advanced disease. No SAEs were observed in patients treated with TTs. SAEs were COVID-19 related rather than treatment related. Treatment with ICIs does not appear to significantly increase risk of SAEs compared with CT. This information should be considered when determining treatment options for patients.


Subject(s)
COVID-19/prevention & control , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , SARS-CoV-2/isolation & purification , Aged , COVID-19/complications , COVID-19/virology , Female , Gastrointestinal Diseases/chemically induced , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Middle Aged , Neoplasms/complications , Neoplasms/mortality , Prospective Studies , SARS-CoV-2/physiology , Survival Rate
7.
Clin Kidney J ; 13(6): 913-925, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1066285

ABSTRACT

The rapid spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has raised questions about Fabry disease (FD) as an independent risk factor for severe COVID-19 symptoms. Available real-world data on 22 patients from an international group of healthcare providers reveals that most patients with FD experience mild-to-moderate COVID-19 symptoms with an additional complication of Fabry pain crises and transient worsening of kidney function in some cases; however, two patients over the age of 55 years with renal or cardiac disease experienced critical COVID-19 complications. These outcomes support the theory that pre-existent tissue injury and inflammation may predispose patients with more advanced FD to a more severe course of COVID-19, while less advanced FD patients do not appear to be more susceptible than the general population. Given these observed risk factors, it is best to reinforce all recommended safety precautions for individuals with advanced FD. Diagnosis of FD should not preclude providing full therapeutic and organ support as needed for patients with FD and severe or critical COVID-19, although a FD-specific safety profile review should always be conducted prior to initiating COVID-19-specific therapies. Continued specific FD therapy with enzyme replacement therapy, chaperone therapy, dialysis, renin-angiotensin blockers or participation to clinical trials during the pandemic is recommended as FD progression will only increase susceptibility to infection. In order to compile outcome data and inform best practices, an international registry for patients affected by Fabry and infected by COVID-19 should be established.

8.
Pathogens ; 10(1)2021 Jan 07.
Article in English | MEDLINE | ID: covidwho-1024620

ABSTRACT

Chronic hepatitis C (CHC) is a major cause of hepatocellular carcinoma (HCC) worldwide. While directly acting antiviral (DAA) drugs are now able to cure virtually all hepatitis C virus (HCV) infections, even in subjects with advanced liver disease, what happens to the liver and progression of the disease after DAA-induced cure of viremia is only beginning to emerge. Several large-scale clinical studies in different patient populations have shown that patients with advanced liver disease maintain a risk for developing HCC even when the original instigator, the virus, is eliminated by DAAs. Here we review emerging studies derived from multiple, complementary experimental systems involving patient liver tissues, human liver cell cultures, human liver slice cultures, and animal models, showing that HCV infection induces epigenetic, signaling, and gene expression changes in the liver associated with altered hepatic innate immunity and liver cancer risk. Of critical importance is the fact that these virus-induced abnormalities persist after DAA cure of HCV. These nascent findings portend the discovery of pathways involved in post-HCV immunopathogenesis, which may be clinically actionable targets for more comprehensive care of DAA-cured individuals.

9.
World J Gastroenterol ; 26(46): 7272-7286, 2020 Dec 14.
Article in English | MEDLINE | ID: covidwho-993611

ABSTRACT

The global incidence of coronavirus disease 2019 (COVID-19) continues to increase despite health care efforts. The disease is caused by coronavirus 2 with high transmission and mortality rates. Little is known about the management of COVID-19 in advanced liver disease. The aim of work was to propose a plan for management of this drastic disease in case of this specific population with review of medications that could be suitable for advanced liver disease. All the guidelines and medications available for treatment of COVID-19 were reviewed with selection of the less toxic medications that could be used in advanced liver disease. Drugs suitable to manage COVID-19 in patients with liver disease might include remdesivir intravenously, nitazoxanide + sofosbuvir, ivermectin, tocilizumab, convalescent plasma, and low molecular weight heparin in certain situations. Advanced liver disease is associated with portal hypertension and splenomegaly with reduction of blood elements and immune dysfunction and impaired T cell function. Thus, when confronted by cytokine storm as an immune response to COVID-19, there may be an increase in the mortality rate of these patients. Through this review, a plan to treat COVID-19 in this special group of patients with advanced cirrhosis is proposed.


Subject(s)
Chemical and Drug Induced Liver Injury , Liver Diseases/complications , COVID-19/complications , Gastroenterology , Humans
10.
Neuromodulation ; 24(2): 331-336, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-917754

ABSTRACT

OBJECTIVES: Deep brain stimulation (DBS) is a well-established therapy for the management of patients with advanced Parkinson's disease and other movement disorders. Patients implanted with DBS require life-long management of the medical device as well as medications. Patients are often challenged to frequently visit the specialized DBS centers and such challenges are aggravated depending on geography, socioeconomic factors, and support systems. We discuss the need for digital health solutions to overcome these barriers to better and safely take care of patients, especially in the current COVID-19 pandemic. MATERIALS AND METHODS: A review of the literature was conducted for technology and logistics necessary in forming a digital health program. RESULTS: Digital health encounters can take place in both a synchronous and asynchronous manner. Factors involving patients include cognitive capacity, physical safety, physical capacity, connectivity, and technological security. Physician factors include examining the patient, system diagnostics, and adjusting stimulation or medications. Technology is focused on bridging the gap between patient and physician through integrating the DBS lead, implantable pulse generator (IPG), programmer, novel devices/applications to grade motor function, and teleconference modalities. CONCLUSIONS: For patients with Parkinson's disease, digital health has the potential to drastically change the landscape after DBS surgery. Furthermore, technology is fundamental in connectivity, diagnostic evaluation, and security in order to create stable and useful patient-focused care.


Subject(s)
COVID-19 , Deep Brain Stimulation/methods , Pandemics , Parkinson Disease/therapy , Telemedicine , Humans
11.
Lung ; 198(6): 879-887, 2020 12.
Article in English | MEDLINE | ID: covidwho-917116

ABSTRACT

Lung transplantation is a lifesaving intervention for patients with advanced lung disease. Due to a combination of immunosuppression, continuous exposure of the lungs to the environment, and complications at the anastomotic sites, lung transplant recipients are at high risk for infectious complications. The aim of this review is to summarize recent developments in the field of infectious diseases as it pertains to lung transplant recipients.


Subject(s)
Donor Selection , Infections/diagnosis , Lung Transplantation/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Humans , Infections/epidemiology
12.
J Clin Med ; 9(11)2020 Oct 25.
Article in English | MEDLINE | ID: covidwho-895375

ABSTRACT

The aims of this population study were to assess the lockdown impact on patients waiting for hemorrhoidal surgery, and the role of telemedicine in patient management. All patients on our waiting list for hemorrhoidal surgery were considered. Eligible patients were contacted by phone. Rørvik score was evaluated and compared to the baseline score. Univariate and multivariate analyses were performed. A numeric rating scale was used to estimate patient satisfaction regarding telemedicine. One-hundred and ten patients were found to be eligible. Finally, 103 patients were included in the study of whom 16 (15.3%) were already considered for priority surgery. Patients waiting for a longer time showed significantly worse scores (p < 0.001). After telemedicine evaluation the priority waiting list increased by 43.8% (plus 23 patients). Weight loss of at least 3 kg and physical activity were found to be protective factors (p = 0.02 and p = 0.002 respectively). A high grade of satisfaction (almost 80%) towards telemedicine was registered. COVID-19-related delays are linked to a deterioration of hemorrhoidal symptoms and patients' well-being. Weight and lifestyle changes were deemed key factors in determining disease severity. Telemedicine was a valuable tool to evaluate and re-evaluate patients waiting for hemorrhoidal surgery and was considered satisfactory by patients.

13.
BMJ Case Rep ; 13(5)2020 May 12.
Article in English | MEDLINE | ID: covidwho-822228

ABSTRACT

Critically ill patients are at risk of developing both acute kidney injury (AKI) and invasive fungal infections (IFIs). Prompt and efficient treatment of the IFI is essential for the survival of the patient. This article examines three distinct clinical situations where liposomal amphotericin B, a broad-spectrum antifungal agent, was successfully used in the setting of AKI. The first was Aspergillus infection in a 63-year-old man with bleeding oesophageal varices related to advanced liver disease. The second was gastrointestinal mucormycosis in a 74-year-old man who developed a small bowel obstruction following an autologous stem cell transplant for mantle cell lymphoma. The third was a Fusarium infection in a 32-year-old woman on immunosuppression for a bilateral lung transplant for cystic fibrosis. In all three cases, liposomal amphotericin B was required for urgent management of the patient's IFI. We discuss the rationale for treatment with a potentially nephrotoxic agent in this setting.


Subject(s)
Acute Kidney Injury/complications , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Critical Illness , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Adult , Aged , Female , Humans , Male , Middle Aged
14.
Cancer Treat Rev ; 89: 102068, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-640225

ABSTRACT

The outbreak of the SARS-CoV-2 pandemic has overwhelmed health care systems in many countries. The clinical presentation of the SARS-CoV-2 varies between a subclinical or flu-like syndrome to that of severe pneumonia with multi-organ failure and death. Initial reports have suggested that cancer patients may have a higher susceptibility to get infected by the SARS-CoV-2 virus but current evidence remains poor as it is biased by important confounders. Patients with ongoing or recent cancer treatment for advanced active disease, metastatic solid tumors and hematological malignancies are at higher risk of developing severe COVID-19 respiratory disease that requires hospitalization and have a poorer disease outcome compared to individuals without cancer. However it is not clear whether these are independent risk factors, or mainly driven by male gender, age, obesity, performance status, uncontrolled diabetes, cardiovascular disease and various other medical conditions. These often have a greater influence on the probability to die due to SARS-CoV-2 then cancer. Delayed diagnosis and suboptimal cancer management due to the pandemic results in disease upstaging and has considerable impact cancer on specific death rates. Surgery during the peak of the pandemic seems to increase mortality, but there is no convincing evidence that adjuvant systemic cancer therapy and radiotherapy are contraindicated, implicating that cancer treatment can be provided safely after individual risk/benefit assessment and some adaptive measures. Underlying immunosuppression, elevated cytokine levels, altered expression of the angiotensin converting enzyme (ACE-2) and TMPRSS2, and a prothrombotic status may fuel the effects of a SARS-CoV-2 in some cancer patients, but have the potential to be used as biomarkers for severe disease and therapeutic targets. The rapidly expanding literature on COVID-19 should be interpreted with care as it is often hampered by methodological and statistical flaws.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/mortality , Neoplasms/mortality , Neoplasms/virology , Pneumonia, Viral/mortality , Angiotensin-Converting Enzyme 2 , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Humans , Neoplasms/immunology , Neoplasms/therapy , Pandemics , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , SARS-CoV-2 , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/genetics
15.
Oncology ; 98(10): 743-747, 2020.
Article in English | MEDLINE | ID: covidwho-611181

ABSTRACT

BACKGROUND: To date, the clinical characteristics of coronavirus disease 19 (COVID-19)-infected urologic cancer patients are unknown. METHODS: We have analyzed all patients with prostate cancer undergoing hormonal or chemotherapy treatment and receiving telephone and in person pre-triage between March 1 and 27, 2020, at the Tortora Hospital, Pagani, Italy. RESULTS: Among 72 patients, 48 and 24 were hormone-sensitive (HS) and castration-resistant prostate cancer (CRPC), respectively; 0 HS and 2 (8.3%) CRPC (p < 0.05) were positive for COVID-19. Both patients were receiving LHRH agonist therapy, and 1 patient was receiving enzalutamide. Urgent intensive care unit admission was required due to clinical worsening. Blood tests showed severe lymphopenia, anemia, and an increase in platelets. Retroviral therapy, antibiotics, heparin, and chloroquine were prescribed at the beginning. One patient also received tocilizumab as a salvage treatment. After 3 weeks of hospitalization, the patients were discharged from the hospital. Both patients suffered from an aggressive COVID-19 course due to concomitant comorbidities. CONCLUSIONS: Investigating whether hormonal therapy, especially in advanced disease, acts as a protective factor or a risk factor during COVID-19 could be useful.


Subject(s)
Androgen Antagonists/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Heparin/therapeutic use , Pneumonia, Viral/complications , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Progression , Drug Therapy, Combination , Hospitalization , Humans , Italy , Male , Middle Aged , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prognosis , Prostatic Neoplasms, Castration-Resistant/secondary , Prostatic Neoplasms, Castration-Resistant/virology , Risk Factors , SARS-CoV-2
16.
Saudi J Gastroenterol ; 26(5): 233-239, 2020.
Article in English | MEDLINE | ID: covidwho-144213

ABSTRACT

The World Health Organization (WHO), on March 11th 2020, upgraded the status of the novel coronavirus disease (COVID-19) from epidemic to pandemic. Over two million individuals have been infected with SARS-CoV-2, the virus causing COVID-19, and as of April, 14th 2020, there were over 5000 confirmed cases in Saudi Arabia (SA). Many countries, including SA, have imposed major restrictions on travel, and everyday life, and the implications of these necessary changes are being felt in liver transplant (LT) centers in SA. Concerns remain that there is an increased risk for individuals over 65 years of age, with underlying medical conditions, or for those who are immunocompromised. Therefore, the Saudi Association for the Study of Liver Diseases and Transplantation (SASLT) established an urgent task force to launch a statement that can be utilized by LT centers as a guidance in the management of patients with advanced liver disease from the time of LT listing to the post-operative care of transplanted patients.


Subject(s)
Betacoronavirus , Consensus , Coronavirus Infections/epidemiology , Liver Diseases/surgery , Liver Transplantation/methods , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Comorbidity , Humans , Liver Diseases/epidemiology , SARS-CoV-2 , Saudi Arabia/epidemiology
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