UConn Health has begun the process of resuming routine appointments and elective procedures, and we are committed to creating the safest possible environment for our patients, employees, and visitors.

Treatment

There have been 3 recently published small case series on the use of convalescent plasma (CP) to treat severe COVID-19 out of China. Several clinical trials are ongoing in the U.S. and in other countries.

In the study by Shen et al., 5 severely ill patients with coronavirus disease 2019 (COVID-19) were treated with CP (Shen et al., 2020). Convalescent plasma (1 400 mL: dose) was administered between 10 and 22 days after admission. All patients had severe respiratory failure and were receiving mechanical ventilation; 1 needed ECMO and 2 had bacterial and/or fungal pneumonia. Four patients received convalescent plasma around hospital day 20, and 1 was transfused at day 10. Although these patients continued to receive antiviral treatment primarily with lopinavir/ritonavir and interferon, the use of convalescent plasma may have contributed to their recovery because the clinical status of all patients had improvement approximately 1 week after transfusion, as evidenced by normalization of temperature as well as improvements in SOFA scores and Pao2/Fio2 ratio. In addition, the patients’ neutralizing antibody titers increased and PCR was negative between 1 and 12 days after transfusion.

In the study by Zhang et al., 4 critically ill patients (including a 31-year old pregnant woman) improved and recovered after CP transfusions. Three were mechanically ventilated; 2 received ECMO and CVVH. All transfused between 16 and 19 days from admission.Two patients received 1 200 mL dose; 2 received multiple doses of 200 or 400 mL. All became PCR negative and were discharged (Zhang et al., 2020).

In the study by Duan et al. 10 patients with severe COVID-19 received 1 200 mL dose of CP. The median time from onset of illness to CP transfusion was 16.5 d (Duan et al., 2020). Three were on mechanical ventilation. All received a variety of antivirals and antibacterials, as well as most on methylprednisolone. All symptoms in the 10 patients (fever, cough, shortness of breath) disappeared or largely improved within 1 to 3 d upon CP transfusion. Prior to CP, three patients were on mechanical ventilation, 3 received high-flow nasal cannula oxygenation, and 2 received conventional low-flow nasal cannula oxygenation. After treatment with CP, two patients were weaned from mechanical ventilation to high-flow nasal cannula, and one patient discontinued high-flow nasal cannula. On chest CTs, all patients showed varying degrees of improvement of pulmonary lesions after CP transfusion. Of the 7 patients who were PCR + prior to CP, all 7 were negative after.

A historic control group was formed by random selection of 10 patients from the cohort treated in the same hospitals and matched by age, gender, and severity of the disease. Baseline characteristics of patients showed no significant differences, while clinical outcomes of these two groups were different: three cases discharged while seven cases in much improved status and ready for discharge in CP group, as compared to three deaths, six cases in stabilized status, and one case in improvement in the control group (P < 0.001).

Given the lack of clinical trial data, it is not possible to determine the true clinical effect of this intervention. Also patients treated with CP have received numerous other therapies simultaneously (including antiviral agents, antibiotics and steroids), making it difficult to determine specific contribution of CP to the clinical course or outcomes. It is unclear what timing is associated with optimal clinical outcomes.

April 13, 2020: COVID-19 Convalescent Plasma Protocol

Contributors: Lisa Chirch, MD, and Mauricio Montezuma-Rusca, MD, MPH

We are now a registered site for the Convalescent Plasma Mayo Clinic protocol. Treating providers (Infectious Diseases and Critical Care) have been enrolled online.

If needed we can still apply to the FDA for eINDs for individual patients.

Information for Potential Donors

UConn Health employees who have recovered from COVID-19 have volunteered to donate convalescent plasma. Information is being collected through the Call Center. Potential donors are screened by the Infectious Diseases Provider, who will order necessary tests to determine donor eligibility. Convalescent Plasma Collection will take place at the American Red Cross.

In the near future, convalescent plasma collection will be open to the general public.

Links of Interest

All potential donors should register at the American Red Cross website

U.S. COVID-19 Expanded Access Program

Consent Form

Detailed Protocol (Mayo Clinic)

References

Duan, K., Liu, B., Li, C., Zhang, H., Yu, T., Qu, J., . . . Yang, X. (2020). Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. doi:10.1073/pnas.2004168117

Shen, C., Wang, Z., Zhao, F., Yang, Y., Li, J., Yuan, J., . . . Liu, L. (2020). Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. doi:10.1001/jama.2020.4783

April 13, 2020: RAS Inhibitors and COVID

Contributor: Eric Mortensen, MD

What We Know

  • SARS-nCov-2 binds to the ACE 2 receptor.
  • ACE inhibitor and ARB use causes increased expression of the ACE 2 receptor.
  • A recent study found that there is elevated level of angiotensin II in COVID19 patients, which may cause increased inflammation, lung injury, and cytokine storm (Liu et al., 2020).
  • Small RCT (abstract only) demonstrated lung protective effects with ACE inhibitor (Wirtz et al., 2017).
  • Studies have demonstrated improved outcomes with ACEI/ARB use in patients with pneumonia (Caldeira, Alarcão, Vaz-Carneiro, & Costa, 2012) and ARDS (Kim et al., 2017).
  • Professional societies are saying don’t stop these drugs in those who are on them but don’t start if not indicated for another indication.

Questions

  • Can use of RAS inhibitors increase serum levels of ACE2 and reduce viral entry by competitive inhibition.
  • Can use of RAS inhibitors have immunomodulatory and/or lung protective effets in COVID patients.

Important Issues/Questions

  • Almost all of studies in humans for pneumonia/ARDS have looked at prevalent use not incident use of these drugs.
  • Unclear safety data- Will starting these drugs after infection be detrimental by increasing binding sites before competitive inhibition?

References

Caldeira, D., Alarcão, J., Vaz-Carneiro, A., and Costa, J. (2012). Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis. BMJ, 345, e4260. doi:10.1136/bmj.e4260

Kim, J., Choi, S. M., Lee, J., Park, Y. S., Lee, C. H., Yim, J.-J., . . . Lee, S.-M. (2017). Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study. Korean J Crit Care Med, 32(2), 154-163. doi:10.4266/kjccm.2016.00976

Liu, Y., Yang, Y., Zhang, C., Huang, F., Wang, F., Yuan, J., . . . Liu, L. (2020). Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life Sciences, 63(3), 364-374. doi:10.1007/s11427-020-1643-8

Wirtz, H., Hasenclever, D., Schwabe, K., Jaschinski, U., Weyland, A., Kuhnt, E., . . . Hammerschmidt, S. (2017). Ace Inhibitor For Lung Protection During Mechanical Ventilation For Acute Lung Injury- Results Of The Double-Blind, Placebo Controlled, Randomised Acemevent Pilot Study. American Journal of Respiratory & Critical Care Medicine, 195, A2895.

May 22, 2020: COVID-19 Treatment Protocol

Contributor: Jeff Aeschlimann, Pharm.D.

UConn Health COVID-19 Treatment Guidelines

The findings of no significant benefits from a couple released manuscripts of trials of hydroxycholorquine were discussed at the meeting. At this time, the general recommendations for treatment of patients with hydroxycholorquine will remain unchanged from the previous version (Version #3) of the protocol.   

There will be some minor changes to the protocol to reduce the amount of laboratory testing in non-ICU patients, and specifically, blood typing and screening will be limited to all patients admitted to the ICU only. Based on discussions during the meeting, general recommendations will be added to the protocol for the following:

  • A recommendation for prophylactic anticoagulation for all patients with COVID-19 infection
  • A recommendation to continue patient’s chronic maintenance medications such as ACE inhibitors, Angiotensin receptor blockers (ARBs), and/or statin medications unless there are acute contraindications such as hypotension and/or acute significant increases in LFTs