








key: cord-313382-prxc0lue
authors: Hossein Norooznezhad, Amir; Hantoushzadeh, Sedigheh; Shamshirsaz, Alireza A.
title: Empiric Antibiotics in Management of Inpatient Pregnant Women Infected with Coronavirus Disease 2019 (COVID-19): Focusing on Inflammation and Preterm Labor
date: 2020-09-12
journal: Med Hypotheses
DOI: 10.1016/j.mehy.2020.110269
sha: 
doc_id: 313382
cord_uid: prxc0lue

nan

The outbreak of novel coronavirus (SRARS-CoV-2) caused Coronavirus disease 2019 (COVID-19) and led to emergency pandemic according to the World Health Organization (WHO) [1] . This disease with the main manifestation of pneumonia [2] may cause a wide range of morbidities which might lead to mortality [3] . Not only the maternal outcomes but also fetal/neonatal outcomes might be affected by COVID-19. Data have shown that prevalence of preterm birth among inpatient pregnant women with COVID-19 up to 47% [4] [5] [6] . Herein, we would evaluate one of possible cause of non-viral induced preterm labor in pregnant women diagnosed with COVID-19 which could be administration of empiric antibiotics with inflammatory properties in absence of bacterial infection in the inpatients.

In a recent paper [7] , we have reviewed the role of inflammation as one of the most important key elements of preterm labor. Although, in most cases the inflammation cascade for preterm labor has been started with a bacterial infection. However, we have highlighted that the use of antibiotics in the absence of bacterial infection might result in the release of pro-inflammatory cytokine and therefore, an inflammatory storm. As we have shown, antibiotics (in absence of infection) seem to cause gut bacterial decontamination and lipopolysaccharide (LPS) release and therefore endotoxemia. During this endotoxemia, the activation of toll-like receptors (TLRs) cause the release/expression of pro-inflammatory cytokines (such as interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)), chemokines, prostaglandins, and proteases which are involved in preterm labor. We have called this pathway as the indirect pathway while some antibiotics have been shown to affect immune cells such as monocytes to release pro-inflammatory cytokines (direct pathway) [7] . Interestingly, a study has evaluated the outcome of empiric antibiotic therapy on gestational duration in two groups of microbe positive and negative pregnant individuals using 3 rapid and high-sensitive polymerase chain reaction (PCR). Among 104 evaluated pregnant cases, it was shown that the antibiotic-treated microbe negative group had a significantly shorter gestation duration (p<0.0001) [8] . Also, At the beginning of the pandemic, we have suggested avoiding any non-indicated antibiotic consumption to prevent pro-inflammatory cytokine storm which might be one of the causes of septic shock in critically ill COVID-19 patients who have been admitted in intensive care unit (ICU) [2] .

Altogether, we have raised some concern regarding the increased risk of inflammation in patients received antibiotics without evidence of bacterial infection(s). After collecting data from critically ill pregnant patients with COVID-19, we have observed that the most of them had used antibiotics at admission or just a few days following admission and while most cases reported no evidence of bacterial infection [3, 9] . Another study which has compared COVID-19 pregnant women with healthy controls showed the significant increase in the prevalence of preterm labor while all the COVID-19 cases had received antibiotic from admission [10] .

As we have shown, some antibiotics can induce inflammation [7] ; on the other hand, some others (such as macrolides) could modulate inflammation. [11] It is reasonable to start empiric antibiotics for some hospitalized pregnant patients (especially those in ICU), however, we suggest to consider all aspects of the treatment first. If antibiotic(s) should be administrated, it is wiser to choose the one with anti-inflammatory activity such as macrolids which is able to reduce/modulate inflammation (especially in airways) as well as pro-inflammatory cytokines (such as IL-1, IL-6, TNF-α) [11] when there is no other significant difference between the choices. This issue may lead to a decrease in pro-inflammatory cytokines release and possibly preventing preterm labor in pregnant women with COVID-19. 4 Authors declare no actual or potential compacting interest related to this study.

This study was not funded.

Primary Symptoms, Comorbidities, and Outcomes of 431 Hospitalized Patients with Confirmative RT-PCR Results for COVID-19

Inappropriate Antibiotic Consumption as a Possible Cause of Inflammatory Storm and Septic Shock in Patients Diagnosed with Coronavirus-19

Disease (COVID-19)

Maternal Death Due to COVID-19 Disease

Coronavirus Disease 2019 (COVID-19) Pandemic and Pregnancy

Coronavirus in pregnancy and delivery: rapid review

Severe Coronavirus Infections in Pregnancy: A Systematic Review

Antibiotics, Inflammation, and Preterm Labor: A Missed Conclusion

Antibiotic therapy increases the risk of preterm birth in preterm labor without intra-amniotic microbes

gestation period in preterm labor with microbes, evaluated by rapid and high-sensitive PCR system

A case of 2019 Novel Coronavirus in a pregnant woman with preterm delivery

Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study

Antibiotics as immunomodulant agents in COPD

Title: Empiric Antibiotics in Management of Inpatient Pregnant Women Infected with Coronavirus Disease 2019 (COVID-19): Focusing on Inflammation and Preterm Labor

Amir Hossein Norooznezhad declares no actual or potential conflict of interests related to this study

Sedigheh Hantoushzadeh declares no actual or potential conflict of interests related to this study

Shamshirsaz declares no actual or potential conflict of interests related to this study



