COVID-19 Clinical Resources and Pertinent Research
A daily updated list of the most useful COVID-19 clinical resources and the most significant research publications with a summary of their key findings. To contribute, click the plus button on the left. Short URL: bit.ly/C19Res

Clinical Considerations

  1. Cardiovascular Involvement
  2. Pediatrics
  3. Coagulopathy (Also See ICU Management)
    1. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up
      COVID-19 may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. This review summarizes current knowledge regarding the possible association between COVID-19 and thrombotic disease and explains how this information should be considered in treating patients with COVID-19 and those without COVID-19 who have thrombotic disease.
    2. Changes in Blood Coagulation in Patients with Severe Coronavirus Disease 2019 (COVID‐19): A Meta‐Analysis
      Meta-analysis of nine studies that evaluated the difference in coagulation parameters between patients with severe and mild COVID-19 infections. Patients with severe COVID-19 infections presented with an elevated D-dimer and prolonged PT compared with patients with mild COVID-19, with no significant difference seen in platelet count or aPTT. The authors also note that an elevated D-dimer level may be indicative of secondary fibrinolysis, which may lead to more severe clinical manifestations of COVID-19. These findings support prior studies demonstrating that elevated D-dimer and coagulopathy are associated with severe clinical manifestations of COVID-19.
    3. Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series
      This single-center, prospective autopsy study examined pathologic cardiovascular changes in 11 patients with COVID-19 who died. The patients, 73% of whom were men, were a mean age of 80.5 years. No patients had venous thromboembolism clinically suspected antemortem. Prophylactic anticoagulant therapy use administered in 91% of patients. Signs of diffuse alveolar damage at various stages were common. All patients had thrombosis of small and mid-sized pulmonary arteries. These thromboses were associated with bronchopneumonia (6 patients) and infarction (8 patients). All patients exhibited Kupffer cell proliferation. Multiple liver changes were noted, as well as changes in other organ systems. Polymerase chain reaction was used to test for the SARS-CoV-2 virus, and it was detected in pharyngeal, bronchial, and colonic mucosa. Pulmonary arterial thrombosis is an important cause of death in COVID-19 even when patients receive prophylactic anticoagulation.
    4. PulmCrit – Thrombosis update in COVID-19: Data from the Mount Sinai system in NYC
    5. Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence
      Based on data from the first 107 admitted patients with COVID-19 and pneumonia during February and March 2020, 20.6% had experienced a pulmonary embolism (PE) by April 9 (when the analysis was performed). The median time from admission to PE was 6 days. In comparison, an analysis of the files of 196 patients admitted to the same ICU during the same time frame in 2019 found similar severity scores but only 6.1% experienced a PE. Additionally, an analysis of data from influenza patients admitted in 2019 found a 7.5% frequency of PE. Cumulative incidence of PE at day 15 of ICU admission was 20.4% in patients with COVID-19. The authors noted apparent relationships between D-dimers, factor Willebrand antigen levels, and factor VIII activity and PE risk. Most patients (20/22) with COVID-19 who experienced PE were receiving prophylactic guideline-directed antithrombotic treatment at the time.
    6. Prevalence of Venous Thromboembolism in Patients with Severe Novel Coronavirus Pneumonia
      The authors of this study evaluated the incidence of VTE in 81 patients admitted to the ICU with novel coronavirus pneumonia (NCP) and compared outcomes with patients without a diagnosed VTE. Overall, 25% (n=20) patients with severe NCP developed lower-extremity VTE, and, of these, 8 died. Patients with DVT were older (age, 68.4 years) and had significantly higher D-Dimer levels (5.2 vs 0.8 x μg/mL), more profound lymphopenia (0.8 vs 1.3 x 109/L), and prolonged activated partial thromboplastin time (39.9 vs 35.6 seconds). A D-dimer cut-off of 1.5 μg/mL had a sensitivity and specificity for diagnosing VTE of 85% and 88.5%, respectively.
    7. Thromboembolic Events and Apparent Heparin Resistance in Patients Infected with SARS‐CoV‐2
      “Based on the limited SARS-CoV-2 data and our own experience, we suggest to monitor the heparin activity of UFH treatment based on anti-Xa levels with a target value of 0.3 – 0.7 U/L in all patients with SARS-CoV-2 instead of treatment based on aPTT levels.”
    8. Large-Vessel Stroke as a Presenting Feature of COVID-19 in the Young
      Brief letter reporting 5 cases of large-vessel stroke in patients younger than 50 years of age with SARS-CoV-2 in New York City.
    9. Association of Anticoagulation With In-Hospital Survival Among Hospitalized Patients With COVID-19
      In this retrospective observational cohort study, 786 of 2,773 patients (28%) hospitalized with COVID-19 within the Mount Sinai Health System in New York received treatment-dose systemic anticoagulation. Mortality rates were similar in patients who received anticoagulation (22.5%) compared with those who did not receive anticoagulation (22.8%). Among patients requiring mechanical ventilation (n=395), there was an improvement in mortality rates in those who received anticoagulation (29.1%) compared with those who did not (62.7%).
    10. Endothelial Cell Infection and Endotheliitis in COVID-19
      In this case series of 3 patients with COVID-19, histology revealed SARS-CoV-2 viral elements in endothelial cells, with evidence of endotheliitis across vascular beds of multiple organs. COVID-19 endotheliitis could contribute to microcirculatory impairment and sequelae such as thrombosis and ischemia.

  4. Biomarkers and Prognostic Indicators
    1. Level of IL-6 Predicts Respiratory Failure in Hospitalized Symptomatic COVID-19 Patients
      Preprint – In 40 patients, “elevated interleukin-6 (IL-6) was strongly associated with the need for mechanical ventilation. In addition, the maximal IL-6 level (cutoff 80 pg/ml) for each patient during disease predicted respiratory failure with high accuracy. The risk of respiratory failure for patients with IL-6 levels of ≥ 80pg /ml was 22 times higher compared to patients with lower IL-6 levels.
    2. D-Dimer Is Associated with Severity of COVID-19
      In this review and combined analysis of four trials of COVID-19 patients, the authors assessed the association of D-dimer values with the severity of COVID-19. In aggregate, D-dimer values were considerably higher in those with severe disease than in those whose disease was not severe (weighted mean difference, 2.97 mg/L). Elevated D-dimer levels appear to be associated with the severity of COVID-19 infection.
  5. Role of NSAIDS
    1. Non-steroidal Anti-inflammatory Drugs and COVID-19
      Extra risk is plausible on current balance of evidence. Emerging evidence suggests that the most serious complications of COVID-19 are sepsis and cardiovascular or respiratory complications. They occur predominantly in elderly people and those with underlying health conditions. Does use of non-steroidal anti-inflammatory drugs (NSAIDs) increase these risks? We don’t know for certain, but additional risks are plausible on the current balance of evidence.
      1. Video Review: Ibuprofen and Coronavirus

  6. Neuro Involvement
    1. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China
      Of 214 patients with COVID-19, 78 (36.4%) had neurologic manifestations. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5.7%), impaired consciousness (14.8%), and skeletal muscle injury (19.3%). Neurologic symptoms manifest in a notable proportion of patients with COVID-19.
    2. Looking Ahead: The Risk of Neurologic Complications Due to COVID-19
    3. The author of this study summarized current literature regarding the neurologic complications of COVID-19 infection. The report included sections on virology, similarities to other coronaviruses, and neuroinvasive potential. Indirect neurological complications included confusion, headache, nausea, and vomiting. More severe neurological signs such as acute cerebrovascular disease, seizures, and impaired consciousness were thought to be due to dysregulation of systemic homeostasis due to severe infection. Direct neurological complications including brainstem neuronal injury, anosmia, hyposmia, and dysgeusia are also discussed. Post-infectious neurological complications including possible acute disseminated encephalomyelitis and multiple sclerosis were reported.

  7. GI Involvement
    1. Manifestations and Prognosis of Gastrointestinal and Liver Involvement in Patients With COVID-19: A Systematic Review and Meta-analysis
      In this systematic review and meta-analysis, 6,686 patients with COVID-19 were analyzed across 35 studies. Pooled prevalence of bowel symptoms was 15%, and 10% of patients presented with gastrointestinal symptoms alone without respiratory features. Those who presented with gastrointestinal involvement had delayed diagnosis and a higher prevalence of complications (OR, 2.51).Digestive symptoms are common in COVID-19, are associated with delayed diagnosis in initial symptom presentation, and may be seen with more severe disease.
    2. Clinical Characteristics of COVID-19 Patients with Digestive Symptoms in Hubei, China: a: A Descriptive, Cross-sectional, Multicenter Study
      Among 204 patients with confirmed COVID-19 in China, 48.5% had digestive symptoms at presentation, including anorexia, diarrhea, vomiting, and abdominal pain. 7 patientspresented with only digestive symptoms and no respiratory symptoms. Patients with digestive symptoms had a significantly longer time from disease onset to admission than patients who did not have digestive symptoms and were less likely to be cured of the disease. Patients with COVID-19 who have digestive symptoms were shown to have a worse prognosis than those without.
    3. Enteric Involvement in Hospitalized Patients with COVID-19 Outside Wuhan
      A retrospective analysis of enteric involvement in COVID-19 patients (n=230) was conducted in Guangdong Province. Diarrhea was experienced by 49 patients (21%), who had increased severity of pneumonia after adjustment for age, gender, and comorbidities. A greater proportion of patients with diarrhea required ventilator support and ICU admission.
    4. Abdominal Imaging Findings in COVID-19: Preliminary Observations
      224 abdominal imaging studies were performed in 134 SARS-CoV-2 positive patients admitted to MGH between 3/27 and 4/10. Bowel wall abnormalities were seen on 31% of CT scans and were associated with ICU admission. Surgical correlation revealed unusual yellow discoloration of bowel and bowel infarction. Pathology demonstrated ischemic enteritis with patchy necrosis and fibrin thrombi in arterioles. Of 37 right upper quadrant ultrasounds, 54% demonstrated a dilated sludge-filled gallbladder suggestive of cholestasis. Bowel abnormalities, including ischemia, and cholestasis were common findings on abdominal imaging of inpatients with COVID-19. Patients who went to laparotomy often had ischemia, possibly due to small vessel thrombosis.

  8. Dermatologic Involvement
    1. Classification of the Cutaneous Manifestations of COVID‐19: A Rapid Prospective Nationwide Consensus Study in Spain with 375 Cases
      Based on data from a nationwide dermatologist survey, 5 categories of cutaneous manifestations associated with COVID-19 were identified, including other maculopapules (47%), pseudo-chilblain (19%), urticarial lesions (19%), other vesicular eruptions (9%), and livedo or necrosis (6%). There were also reports of increased numbers of herpes zoster cases in patients with COVID-19. While pseudo-chilblain lesions tended to affect younger patients with less severe disease, vesicular lesions appeared more in middle-aged patients with moderate disease severity. Urticarial, maculopapular, and livedoid/necrotic lesions were all associated with more severe disease. A mortality rate of 10% was noted in the livedoid/necrotic group.
    2. Chilblain-Like Lesions on Feet and Hands During the COVID-19 Pandemic (“COVID Toes”)
      In this case series from Spain, the authors present data from 6 patients with chilblain-like lesions. Lesions were initially red papules and developed into purpuric macules over approximately 1 week. Lesions were most commonly seen on the toes, soles, fingers, extremities, and/or heel. Symptoms of coronavirus were generally absent or mild, except in one 91-year-old patient who required hospitalization. While 2 patients tested positive for COVID-19 prior to onset of these symptoms, one 15-year-old patient tested negative despite bilateral pneumonia, and 3 could not be tested, although 2 of these had known high risk of exposure. Despite the inability to definitively correlate without confirmatory testing in all patients, the high rate of consultations for chilblains-like lesions weeks after reaching the national peak of COVID-19 infections in Spain highlights this as a suspicious phenomenon for a late-stage manifestation of COVID-19, particularly considering similar observations in other countries.

  9. Other
    1. Association of Chemosensory Dysfunction and COVID‐19 in Patients Presenting with Influenza‐like Symptoms
      “In ambulatory individuals with influenza‐like symptoms, chemosensory dysfunction was strongly associated with COVID‐19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks paralleling resolution of other disease‐related symptoms.”
      1. Case Report: Sudden and Complete Olfactory Loss Function as a Possible Symptom of COVID-19
      2. Letter: Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection
    2. Detection of SARS-CoV-2 in Human Breastmilk
      The authors detected SARS-CoV-2 RNA in milk samples from a mother for 4 consecutive days. Detection of viral RNA in milk coincided with mild COVID-19 symptoms and a SARS-CoV-2 positive diagnostic test of the newborn. The mother had been wearing a surgical mask since the onset of symptoms and followed safety precautions when handling or feeding the neonate (including proper hand and breast disinfection, strict washing, and sterilisation of milk pumps and tubes). However, whether the newborn was infected by breastfeeding or other modes of transmission remains unclear.
    3. Relationships Among Lymphocyte Subsets, Cytokines, and the Pulmonary Inflammation Index in COVID-19–Infected Patients
      This study evaluated levels of pulmonary inflammation using the pulmonary inflammation index, CD4+, CD8+ T lymphocytes, and cytokine levels in 123 patients with COVID-19 infection (102 mild and 21 severe). Of the cytokines measured (IL-4, IL-6, IL-10, IL-17, TNF, and IFN), IL-6 was found to be most commonly elevated (30% in the mild group and 76% in the severe group). Among patients with mild disease, there was a significant positive correlation between CD4+ and CD8+ T-lymphocyte levels and elevated cytokines, an effect which was not observed in the severe group. CD4+, CD8+, and IL-6 levels improved in the severe group prior to discharge, while there was no significant change in levels in the mild group. Elevated inflammatory cytokines, specifically IL-6, appear to be associated with more severe COVID-19 infection. Further studies evaluating IL-6 levels in patients with life-threatening COVID-19 infection (including ARDS) and the potential role for therapeutic intervention are warranted.
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