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High-Dose IVIg Reversed Worsening COVID-19 in Case Reports

MAR 25, 2020 | KENNETH BENDER, PHARMD, MA
High-dose intravenous immunoglobulin (IVIg) appeared to reverse the deteriorating course of 3 patients with coronavirus disease 19 (COVID-19), in case reports from a hospital at the center of the outbreak in Wuhan, China.

Two of the patients admitted to the Jin Yin-tan Hospital in Wuhan were initially diagnosed with COVID-19 common type, but quickly deteriorated to severe type, and the third patient met that criteria on admission. IVIg was administered subsequent to the increased severity.

"Strategies against COVID-19 should...be specified according to the course of infection," explained Taisheng Li, MD, PhD, Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Bejing, China, and colleagues.

"The best timing of antivirals, if there are any, may lie on the phase before acceleration. When clinical deterioration begins, the first few days of deterioration may present a critical point when potent suppression of inflammatory cascade could save the patients from fatal immune-mediated injuries, as shown here," the investigators indicated in their case reports.

With each patient, Li and colleagues found an accelerating phase of the disease with virus-induced secondary insults that included significant lymphocytopena and elevated ESR (erythrocyte sedimentation rate) and hsCRP (high-sensitive C-reactive protein) inflammatory markers.

The study team explained that IVIg, a blood product containing polyclonal immunoglobulin G isolated and pooled from healthy donors, is a potent and safe immune modulator that has been available for over 30 years and has well-established dosing from a range of conditions.

At the point where each patient's condition deteriorated, IVIg was administered at 25gm/day for 5 days. Patient 1 became afebrile on the sixth day after the start of IVIg; and clinical status gradually improved, with supplemental oxygen no longer needed on the seventh day. Test results on the ninth day after the start of IVIg showed recovered lymphocyte count, decreased ESR (to 31mm/h), and hsCRP in normal range. The patient was discharged on the ninth day after starting IVIg, and after oropharyngeal swabs on the sixth and seventh day were both negative for SARS-CoV-2.

Patients 2 and 3 had similar reversals of deterioration after the IVIg regimen, and were discharged within several days, and with negative nasal PCR tests.

The study team noted that in these patients, as occurred in patients with SARS, deterioration can be marked by reduced peripheral lymphocyte counts and elevated inflammatory makers that reflects an overwhelming immune response.

"Previous experience in SARS showed that the main pathogenesis of organ dysfunction lay on the overall cytokine dysregulation," Li and colleagues recount. "Similarly, the point when status deterioration starts in patients with COVID-19 should be a critical window of opportunity for intervention."

The investigators acknowledged that their report is limited by the small number of patients, and that additional evidence is needed to confirm their finding.

"However, it provided an important therapeutic clue under the current situation of rapid[ly] spreading disease," they claimed. "The timing of IVIg administration is very critical in practice. Patients might not receive much benefit when overall systemic damage has already taken place."
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