key: cord-0741965-xwsqjuf6
authors: Reynaga, Esteban; Carrillo, Jorge; Santos, Jose Ramón; Roure, Silvia; Mateu, Lourdes; Paredes, Roger; Clotet, Bonaventura; Izquierdo-Useros, Nuria; Pedro-Botet, Maria Luisa
title: Outcome of hospitalized patients with COVID-19 pneumonia treated with high-dose immunoglobulin therapy in a prospective case series
date: 2020-10-13
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.10.010
sha: 62927867005e981e47c6664cfae068518f162a6b
doc_id: 741965
cord_uid: xwsqjuf6

[Figure: see text]

To the Editor:

Control of hyperinflammation might be crucial to decrease COVID-19 severity, and intravenous immunoglobulins (IVIG) can be useful due to their immunomodulatory properties. IVIG can neutralize cytokines and autoantibodies, prevent innate cell activation by blocking activating Fcreceptors, reduce the half-life of autoantibodies, promote the generation of regulatory T cells, and block the activation of the complement, among many other functions 1 . Preliminary data support the benefit of high dose IVIG at the time of respiratory distress initiation in COVID-19 infected patients [2] [3] [4] , and an early initiation of this treatment may be critical for survival 4 . Here, we describe five patients treated with IVIG for COVID-19.

Data collection were prospectively defined and collected, with a follow-up of 4-5 weeks, including post-discharge, at the Germans Trias i Pujol hospital between April 2 nd and June 18 th 2020. All patients received hydroxychloroquine as no guidelines at that time recommended the use of other treatments. We received an exemption from ethics approval because IVIG was used in an off-label indication, it was approved by the Pharmacy and Therapeutics Committee of the hospital, and all informed subjects signed an informed consent (PI-20-266). Table 2 . Age ranged from 24 to 80 years old, and three patients were male. The oropharyngeal swab was positive for SARS-CoV-2 by RT-PCR assay in four patients, while one diagnosis was done with positive IgA serology for SARS-CoV-2 (Supplemental Table 3 ).

At inclusion, patients had a medium risk of acute distress respiratory syndrome (ADRS) according to the Berlin definition (Supplementary Table 2 ) and a mid to high NEWS score (Figure 1) . All subjects had COVID-19 multilobar pneumonia and PaO 2 /FiO 2 values ≤ 300 mmHg, requiring supplemental oxygen therapy (Supplemental Table 2 ). Of note, two patients had severe renal failure before treatment administration. Yet, no infusion-related complications during IVIG administration nor adverse effects related to therapy were observed. All Table 3 ).

The levels of immunoglobulins were determined before treatment; blood counts, chemistry and biomarkers were detected previously to IVIG administration and during 14 days; and chest X-ray was done on day 3, 5 and when discharged (Supplemental Table 3 ).

After IVIG infusion, the NEWS score showed a progressive decline in all subjects, reaching minimal values by day 14 (Figure 1 ). All patients required supplemental oxygen at admission, but their respiratory conditions (PaO 2 /FiO 2 and pO 2 ) improved rapidly after starting treatment (Figure 1) Table 3 ). The main inflammatory biomarkers (IL-6, C-reactive protein and Fibrinogen) decreased by day 7, reaching normal values by day 14 (Figure 1) . However, D-Dimer did not normalize in all individuals by day 14 (Figure 1) Although patients included in this study showed a PaO 2 /FiO 2 value ≤ 300 mmHg and had a medium risk of ARDS according to the Berlin definition, all of them successfully recovered upon IVIG infusion, and none developed ARDS or required ICU admission. Thus, our experience corroborates the clinical applicability of IVIG for treating COVID-19 pneumonia, and warrants future randomized clinical trials to confirm these observations. Antivirals like remdesivir, neutralizing antibodies against cytokines, or our approach using IVIG are more expensive than immunomodulators such as dexamethasone.

However, dexamethasone only reduces 2.9% of deaths in patients who require oxygen but not invasive mechanical ventilation 5 

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