Gastrointestinal and Hepatic Manifestations of COVID-19: Evolving Recognition and Need for Increased Understanding in Vulnerable Populations

The novel coronavirus, SARS-CoV-2, has caused a global pandemic with high morbidity and mortality. It was first observed to cause a severe acute respiratory syndrome. However, gastrointestinal and hepatic manifestations have been increasingly recognized.Gastrointestinal symptoms include diarrhea, epigastric pain, nausea, and vomiting. Diarrhea is the most common GI manifestation of SARS-CoV-2 and can present without or without respiratory symptoms. Patients with GI symptoms have been associated with longer duration of illness and may be associated with more severe illness. Mechanism of diarrhea is thought to be related to direct viral cytotoxicity occurring when the SARS-CoV-3 enters GI cells via the ACE-2 receptor. Inflammatory response and cytokine release likely contributes to symptoms.SARS-CoV-2 can cause hepatic injury. Studies have shown mild to moderate elevation of liver enzymes. The pattern of liver abnormalities can be hepatocellular, cholestatic or mixed. Patients with severe infection have significantly higher rates of liver injury and worse outcomes. Proposed mechanisms for injury include immune mediated systemic inflammatory response, direct cytotoxicity from viral replication and hypoxia-reperfusion dysfunction.Recent data suggests that GI and hepatic injury may be under-recognized manifestation of SARS-CoV-2 infection. Patients with diarrhea and liver disease may have a worse prognosis. The rapidly evolving literature continues to reveal a growing body of information which enables updated guidance for management. More investigation is needed which focuses on vulnerable patients, including the elderly, those with underlying illness, as well as, racial and ethnic minorities.     

Multidisciplinary consensus on sputum induction biosafety during the COVID-19 pandemic

Sputum induction (SI) is the gold standard approach to the non-invasive study of airway inflammation. The differential count of inflammatory cells for SI allows patients with asthma to be classified according to inflammatory phenotypes and predicted therapeutic responses. Since SI involves the generation of aerosols, there is a need to establish a protocol to ensure biosafety in clinical practice during the current COVID-19 pandemic. The multidisciplinary consensus on SI described in this article was developed by 22 experts in SI from different Spanish hospitals who drew on available scientific evidence in achieving consensuated opinions, compiled by means of an electronic survey. We hope that these unified criteria and recommendations will guide health professionals in implementing SI sampling and processing procedures as safely as possible during the COVID-19 pandemic.     

Risk factors for severe and critically ill COVID-19 patients: A review

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.     

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with coronavirus disease‐2019 (COVID‐19). We sought to determine the clinical characteristics relevant to the clinical course of COVID‐19 by comparing the family cluster to unrelated patients with SARS‐CoV‐2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. Twenty‐nine patient files were investigated in group 1 and group 2 was created with 52 consecutive patients with COVID‐19 having age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, and disease course. There was no difference between the two groups in terms of comorbidity and smoking history. In terms of inhospital treatment, use differed not significantly between two groups. We found that all 29 patients in the group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay, and transferred to intensive care unit were found to be statistically significantly higher in the group 1. In the present study, COVID‐19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared with consecutive patients with COVID‐19 presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID‐19 should include such family clusters.     

Duration of SARS‐CoV‐2 RNA shedding and factors associated with prolonged viral shedding in patients with COVID‐19

To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID‐19). A retrospective cohort of COVID‐19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8‐14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5‐18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5‐27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19‐2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID‐19 patients.     

Clinical characteristics and risk factors of mild‐to‐moderate COVID‐19 patients with false‐negative SARS‐CoV‐2 nucleic acid

This study investigates the clinical and imaging characteristics of coronavirus disease 2019 (COVID‐19) patients with false‐negative nucleic acids. Mild‐to‐moderate COVID‐19 patients, including 19 cases of nucleic acid false‐negative patients and 31 cases of nucleic acid positive patients, were enrolled. Their epidemiological, clinical, and laboratory examination data and imaging characteristics were analyzed. Risk factors for false negatives were discussed. Compared with the nucleic acid positive group, the false‐negative group had less epidemiological exposure (52.6% vs 83.9%; P = .025), less chest discomfort (5.3% vs 32.3%; P = .035), and faster recovery (10 [8, 13] vs 15 [11, 18.5] days; P = .005). The number of involved lung lobes was (2 [1, 2.5] vs 3 [2, 4] days; P = .004), and the lung damage severity score was (3 [2.5, 4.5] vs 5 [4, 9] days; P = .007), which was lighter in the nucleic acid false‐negative group. Thus, the absence of epidemiological exposure may be a potential risk factor for false‐negative nucleic acids. The false‐negative cases of COVID‐19 are worth noting because they have a risk of viral transmission without positive test results, lighter clinical manifestations, and less history of epidemiological exposure.