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Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. 281
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Chong et al
TABLE 1. Clinical characteristics of SARS-CoV-2 patients. Corresponding normal reference range of serum values are provided in square brackets
where applicable.
pneumonia, which is more than seven days after presen- counts (1% and less) in our study patients were similar to
tation with SARS-CoV-2 pneumonia.4,6 An observational white cell count differentials observed in other viral-induced
study on radiological findings of 62 SARS-CoV-2 pleural effusions.8,10 Moreover, most of these patients were
patients demonstrated that the risk of developing pleural on steroids, which can explain low eosinophils in the pleural
effusion was up to 23% in patients with advanced space. A prospective study has reported no increased risk
SARS-CoV-2 pneumonia.6 of significant bleeding associated with pleural effusion
The exact pathogenesis of pleural effusion due to drainage in the setting of therapeutic anticoagulation.11 We
SARS-CoV-2 pneumonia is not known. However, our hypothesize that sanguineous pleural effusion in SARS-
patients have significantly increased inflammatory markers, CoV-2 may be the result of endothelial dysfunction-related
which may signify an increase in capillary and endothelial microthrombi from underlying inflammation that causes
dysfunction leading to exudation of fluid into the pleural foci of hemorrhage in the lung parenchyma extending into
space. Only 40% of pleural effusions were lymphocytic the pleura. This has been described in autopsy findings of
predominant (lymphocytes >50% of nucleated cells), lower SARS-CoV-2 patients in New Orleans.12
than seen in other viral infection-related pleural effusions All effusions were exudative by Light’s criteria.7.
such as avian influenza.8,9 This finding can be explained by These findings can be explained by the markedly ele-
relative lymphopenia seen in patients with SARS-CoV-2 vated pleural fluid LDH in all pleural effusions (pleural
infection. Majority (3/5,60%) of effusions were hemorrhagic fluid to serum LDH ratio of 0.6<) with a mean pleural fluid
(RBC >100,000 per mm3) [Table 2]. While it is possible that LDH level of 1550 (Table 2). The significantly elevated
intrapleural bleeding could reflect a procedural complica- level of LDH in pleural fluid can be due to the presence of
tion in patients receiving systemic anticoagulation, anticoa- a large amount of hemolyzed red blood cells in the pleu-
gulants were held prior to drainage. Furthermore, high ral fluid. However, this finding persisted after excluding
eosinophil counts are frequently encountered in hemor- the effusions with sanguineous appearance. A height-
rhagic pleural effusions, but the finding of low eosinophil ened immune response observed in many SARS-CoV-2
TABLE 2. Characteristics of pleural fluid samples from SARS-CoV-2 patients. Corresponding normal reference range of serum values are provided in
brackets where applicable.
patients with extremely elevated inflammatory markers related pleural effusions, except a higher proportion of
causing a high cell turnover may explain this finding.2,4,13 SARS-CoV-2 patients have hemorrhagic effusion.
A markedly elevated pleural fluid to serum LDH ratio of 1.3
and more may suggest underlying SARS-CoV-2-associ-
DECLARATION OF COMPETING INTEREST
ated pleural effusion. Similar findings have been found in
WC: None, JH: Consultant/Advisory Boards: IBIOS
patients with either H5N1 Influenza A or Pneumocystis jir-
[IPF]; Roche/Genentech [IPF(Nintedanib)]; Boehringer
ovecii-associated pleural effusions. In these observational
Ingelheim [IPF (Pirfenidone)], AC: None.
studies, the mean pleural fluid LDH was 400 IU/L and
more with pleural fluid to serum LDH ratio greater than
1.9,14 Our study patient’s pleural fluid glucose levels were FUNDING
within the normal range, which are similar to findings None.
noted on other viral-induced pleural disease.8 Woon H. Chong,1
Our study was limited by the small sample size. Pleu- John Terrill Huggins,2
ral fluid was not tested for the presence of SARS-CoV-2 Amit Chopra1,*
using RT-PCR. However, there was no alternative cause 1
Division of Pulmonary and Critical Care Medicine, Department of
of pleural effusion identified in these patients. Repeat Medicine, Albany Medical Center, Albany, NY, United States
2
RT-PCR test during the time of pleural drainage on these Division of Pulmonary and Critical Care Medicine, Department of
patients remained positive. All patients were receiving Medicine, Ralph H. Johnson VA Medical Center, Charleston, SC,
systemic anticoagulation for hypercoagulability, which United States
E-mail: Chopraa1@amc.edu
may explain the high prevalence of hemorrhagic effusions
in these patients.
Our study demonstrated that SARS-CoV-2-associated
pleural effusions are commonly unilateral and occur after a REFERENCES
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novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;
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found in pleural fluid as compared to serum. These findings 2. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson
were consistent with features seen in other viral infection- JJ. COVID-19: consider cytokine storm syndromes and
Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved. 283
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Chong et al