key: cord-0974906-37y3izxk
authors: Voiriot, Guillaume; Fajac, Anne; Gibelin, Aude; Parrot, Antoine; Fartoukh, Muriel
title: Alveolar lymphocytosis with plasmacytosis in severe COVID-19
date: 2020-08-14
journal: Respiratory Medicine and Research
DOI: 10.1016/j.resmer.2020.100784
sha: 4872bfd8ae40abe58d158ef67f12d4a2bb4ef6d8
doc_id: 974906
cord_uid: 37y3izxk

nan

To the Editor, The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is associated with a pulmonary and systemic 'cytokine storm' (1) . Little is known about the lung immune-inflammatory response in the most severely ill patients. To gain insight into this issue, we report preliminary findings regarding bronchoalveolar lavage fluid (BALF) findings in COVID-19 patients admitted to the intensive care unit (ICU). We conducted a comprehensive observational monocenter study in the 20-bed ICU of Tenon University Hospital (AP-HP, Paris). During the study period, all consecutive adult patients with laboratory-confirmed COVID-19 were screened, and those having undergone a BAL within ICU stay were included. Data regarding demographics, comorbidities, microbiological investigations and ICU course were collected. Patients were grouped according to their lymphocyte percentage in BALF, with a cut-off of 25% as used previously (2) . Continuous and categorical variables are described as median [interquartile] and number (percentages), respectively, and compared between groups using the nonparametric pairwise Mann and Whitney test and Fisher's exact test, respectively. From March 17 th to April 9 th 2020, 84 patients were admitted to the ICU with COVID-19, a median of 8 days [6] [7] [8] [9] [10] [11] (median [25 th -75 th percentiles]) after symptoms onset, and 71 (84.5%) patients received mechanical ventilation. Twenty patients underwent a fiberoptic bronchoscopy with BAL (three 50mL aliquots of saline) performed for ruling out bacterial pneumonia as well as opportunistic infections, 13 days [8-17] after symptoms onset and 7 days [3] [4] [5] [6] [7] [8] [9] [10] [11] after hospital referral. In 3 patients, BAL was performed prior to ICU admission. There were 19 men and one woman, aged 61 [52-68] years, all non-smokers, with a Simplified Acute Physiological Score II (SAPS II) of 31 [24-41] on ICU admission and a Sequential Organ Failure Assessment (SOFA) of 6 [3-7] on the day of BAL. No patient had received high-dose immunosuppressive or immunomodulatory drugs prior to BAL, while 5 were previously immunocompromised (Table) . The median BALF total cell count was 260 cells/µL , and the median lymphocyte percentage was 11% . Cultures of BALF were positive for bacteria in 7 (35%) patients, among whom 5 with Staphylococcus aureus. One third of the patients had a BALF lymphocyte percentage above 25% (high-LyBALF group, n=6, median 42.5 % [36 -47], compared to low-LyBALF group, n=14, median 6.5% [2 -12] Our findings suggest that BAL analysis may be informative particularly in patients with persistent or worsening symptoms, to characterize the immune-inflammatory response in severe COVID-19. A lymphocytic phenotype with plasmacytosis, as recently reported in one case (3) , may correspond to a late worsening of the respiratory disease as described by Lescure et al. (4) . Whether this lymphocytic alveolar reaction corresponds to a disease progression towards a COVID-19 organizing pneumonia (5) or to the leakage of the damaged pulmonary vascular endothelium as a consequence of the viral endotheliitis (6) is presently unknown. This pilot study has several limitations. The cytologic analysis of BALF was rudimentary in the special period of COVID-19 crisis, so both lymphocytic typing and quantification of plasma cells were not available routinely. Similarly, the low availability of RT-PCR test for SARS-CoV-2 RNA detection prevented us to repeat it and assess the viral shedding at time of BAL. Eventually, considering the low number of observations, we did not search for putative associations between BALF lymphocytosis and radiological or laboratory data, or even clinical outcomes. As far as we know, our study is the first to report data regarding the BAL findings in severe COVID-19. A third of patients displayed a marked lymphocytosis, with mainly activated cells including plasma cells. Additional information on alveolar cellular profiles at different stages of the disease are needed, which may help clinicians to personalize treatments, especially the use of immunomodulatory and/or immunosuppressive agents, in the most severely affected patients. 

Dysregulation of immune response in patients with COVID-19 in Wuhan, China

The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenivc organizing pneumonia

Exuberant plasmocytosis in bronchoalveolar lavage specimen of the first patient requiring extracorporeal membrane oxygenation for SARS-CoV-2 in Europe

Clinical and virological data of the first cases of COVID-19 in Europe: a case series

Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection

Endothelial cell infection and endotheliitis in COVID-19

Author's contribution GV had full access to all the data and takes responsibility for the integrity of the data. GV drafted the manuscript. AF performed the pathological examination of bronchoalveolar lavage fluids and helped to revise the manuscript. AG and AP performed bronchoalveolar lavages and helped to revise the manuscript. MF revised the manuscript. All authors read and approved the final version to be submitted.

All authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Funding None

All patients (or next of kin) gave consent for their data to be reported.

Data and materials supporting the findings of this study can be entirely shared if asking.