Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice.

The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.

Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality.

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1ß and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.

Clinical characteristics of re-hospitalized COVID-19 patients with recurrent positive SARS-CoV-2 RNA: a retrospective study.

At present, it has been noticed that some patients recovered from COVID-19 present a recurrent positive RNA test of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) after being discharged from hospitals. The purpose of the current study was to characterize the clinical features of re-hospitalized patients with recurrent SARS-CoV-2 positive results. From January 12 to April 1 of 2020, our retrospective study was conducted in China. The exposure history, baseline data, laboratory findings, therapeutic schedule, and clinical endpoints of the patients were collected. All the patients were followed until April 10, 2020. Among all COVID-19 patients included in the current study, there were 14 re-hospitalized patients due to recurrent positive tests of SARS-CoV-2 RNA. Fever (11 [78.6%]), cough (10 [71.4%]), and fatigue (7 [50.0%]) were the most common symptoms on the patient's first admission, and less symptoms were found on their second admission. The average duration from the onset of symptoms to admission to hospital was found to be 8.4 days for the first admission and 2.6 days for the second admission (P = 0.002). The average time from the detection of RNA (+) to hospitalization was 1.9 days for the first admission and 2.6 days for the second admission (P = 0.479), and the average time from RNA (+) to RNA (-) was 11.1 days for the first admission and 6.3 days for the second admission (P = 0.030). Moreover, the total time in hospital was 18.6 days for the first admission and 8.0 days for the second admission (P = 0.000). It may be necessary to increase the isolation observation time and RT-PCR tests should be timely performed on multiple samples as soon as possible.

Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study.

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

The Symptoms and Medications of Patients with Inflammatory Bowel Disease in Hubei Province after COVID-19 Epidemic.

OBJECTIVES: The COVID-19 epidemic triggered by coronavirus SARS-CoV-2 is rapidly spreading around the globe. This study is aimed at finding out the suspected or confirmed SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD) in Hubei province, China. We also investigated symptoms, medications, life quality, and psychological issues of IBD patients under the ongoing pandemic. METHODS: We conducted a self-reported questionnaire survey via an online survey platform. SARS-CoV-2 infection-related data was collected from IBD patients. The status quo of medications and symptoms of the subjects were investigated. Life quality, depression, and anxiety were measured by clinical questionnaires and rated on scoring systems. RESULTS: A total of 204 IBD patients from Hubei province were included in this study. No suspected or confirmed SARS-CoV-2 infection case was found in this study. As a result of city shutdown, two-thirds of the patients (138/204) in our series reported difficulty in accessing medicines and nearly half of them (73/138) had to discontinue medications. Apart from gastrointestinal symptoms, systemic symptoms were common while respiratory symptoms were rare in the cohort. Though their quality of life was not significantly lowered, depression and anxiety were problems that seriously affected them during the COVID-19 epidemic. CONCLUSIONS: Inaccessibility to medications is a serious problem for IBD patients after city shutdown. Efforts have to be made to address the problems of drug withdrawal and psychological issues that IBD patients suffer from during the COVID-19 outbreak.

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study.

OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

Management and Treatment of COVID-19: The Chinese Experience.

With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of "Fangcang" shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls.