Issue 7: Clinical considerations in COVID-19 patients (APRIL 17, 2020)

INSIGHTS INTO THE CLINICAL COURSE OF COVID-19

  • COVID-19 progression may occur in phases1. Following SARS-CoV-2 infection, the infected person enters the incubation phase, which is typically 1-14 days, but could be longer2.
  • The infected person then develops viremia; this is considered to be the early phase, where the main symptoms include fever, cough, pharyngalgia, fatigue, and diarrhea; other non-specific symptoms can also present3,4. During this period, peripheral white blood cells are normal to slightly lower than normal, and lesions are not limited to the lungs.
  • During the second phase which occurs 7-14 days after first onset of symptoms, replicated viruses spread through the bloodstream, concentrating in ACE2-expressing tissues such as the lungs, the gastrointestinal (GI) tract, the heart, and the central nervous system1. This second attack is the main cause of worsening symptoms including pulmonary lesions and chest CT scan results. Peripheral T and B blood lymphocytes levels decrease drastically during this phase, and inflammatory factors increase significantly. High plasma levels of proinflammatory cytokines (IL2, IL7, GCSF, IP10, MCP1, MIP1A, and TNF-α) have been observed in 2019-nCoV patients admitted to intensive care units, suggesting development of a cytokine storm effect in these individuals with severe disease5.
  • Reportedly 14% of SARS-CoV-2-infected patients experience a more severe form of the disease, and ~6% become critically ill6. However, the number of critically ill COVID-19 patients requiring continuous renal replacement therapy (CRRT) in the US may be higher, up to 25%7.

ABNORMAL COAGULATION STATUS IN COVID-19

  • The pathophysiology of DIC is complex and multifactorial, involving the hemostatic system and innate immune responders to the infecting pathogen8. Vascular endothelium, platelet, and leukocyte activation results in systemic and local dysregulated thrombin generation in the lungs of patients with severe pneumonia. This results in deposition of fibrin, subsequent tissue damage, and a microangiopathic pathology.
  • Several authors report occurrence of a hypercoagulable state (disseminated intravascular coagulation, DIC) in COVID-19 patients with severe disease2,9-12, where at least one measurable factor [D-Dimer, fibrinogen degradation product (FDP)  prolonged prothrombin time (PT)] increased as the disease progressed. Decreases in fibrinogen and platelet levels were also observed.
  • Some non-survivors suffered  ischemic changes such as ecchymosis of the fingers and toes concurrent with worsening organ dysfunction of the heart and kidneys, skin bulla, and dry gangrene1,10.
  • Higher risk of severe pneumonia, excessive uncontrolled inflammatory  responses, and hypercoagulability was reported in patients with diabetes as the only comorbidity11. Serum levels of IL-6, C-reactive protein, serum ferritin, and D-dimer, were significantly higher (P<0.01) in diabetic patients, suggesting a poorer prognosis in this subpopulation. Levels of PT, FDP and D-Dimer were significantly different between survivors and non-survivors. In addition, DIC was common in 71.4% of non-survivors and only 0.6% of survivors12.

POINTS TO CONSIDER WHEN TREATING THE CRITICALLY ILL

  • The American Society for Nephrology (ASN) suggests that timing of RRT initiation in COVID-19 patients should be similar to other patients with AKI13. CRRT or prolonged intermittent RRT (PIRRT/SLED), with appropriate catheter length and placement, is recommended in these patients. If unavailable, IHD can be performed 13.
  • Institution-specific policies  should apply. Current CRRT doses used are 20-40 mL/kg/hr14. ASN suggests reducing CRRT for 10 hours at higher flow rates (40 to 50 ml/kg/hr) if needed12. Once metabolic control is reached and if solutions are limited, consider a lower dose (i.e., 15-18 mL/kg/hr)13.  Consider lung-protective ventilation and extracorporeal membrane oxygenation (ECMO) strategies as needed.
  • Experts warn of aggressive fluid resuscitation and suggest use of balanced crystalloids, trial of high dose loop diuretics, anticoagulation, and/or citrate dialysate (if established)1,13.
  • Of concern are reports from the field suggesting that many patients may be dry. Thus, caution should be exercised with dosing  and UF in  CRRT.
  • Urgent start PD may be appropriate if CRRT, PIRRT, or IHD are not available, or if  patients are hemodynamically unstable13,15.  Use in respiratory failure and prone ventilated patients is not recommended. Potential complications could include peritonitis, catheter dysfunction, hypernatremia with high-volume PD, and leaks.

REFERENCES:

  1. Li  et al. Emerg Microb Infect. 2020;9:687-690.
  2. Han etal. Clin. Immunol. 2020; Apr 8.
  3. Zhang et al. Emerg Microb Infect. 2020;9:386-389.
  4. Wong et al. J Gastroenterol Hepatol. 2020 Mar 25.
  5. Huang et al. Lancet. 2020;395(10223):497-506.
  6. Guan et al. Lancet . New Eng J Med 2020; Fed 20.
  7. HOSPITAL CARE AND TREATMENT OPTIONS FOR COVID-19 POSITIVE PATIENTS WITH ESKD AND AKI. ASN Webinar, Accessed 4/15/2020.
  8. Gando et al. Nat Rev Dis Prim. 2016;2(1):16037.
  9. Tan e al. Am J Hematol . 2020 Apr 8.
  10. Zhang Y et al. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28.
  11. Guo et al. iDabetes Metab Res Rev. 2020;e3319.
  12. Tang et al. J Tromb Haemost. 2020;18:844-847.
  13. https://www.asn-online.org/g/blast/filesKI_COVID19_Recommendations_Docum…
  14. Ahmed et al. Critical Care Research and Practice Volume 2019.
  15. Abrahams et al. www.DeepL.com Accessed 04/2020.