Molecular evidence suggesting the persistence of residual SARS‐CoV‐2 and immune responses in the placentas of pregnant patients recovered from COVID‐19

Abstract

Objectives Recent studies have shown the presence of SARS‐CoV‐2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high‐risk group for COVID‐19. Based on these findings, we assessed SARS‐CoV‐2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID‐19 and cytokine fluctuations in maternal and foetal tissues. Materials and Methods Remnant SARS‐CoV‐2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS‐CoV‐2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. Results Residual SARS‐CoV‐2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. Conclusions Our study showed that SARS‐CoV‐2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.

Chronic pain and infection: mechanisms, causes, conditions, treatments, and controversies

“…20 21 Similarly, viral remnants such as mRNA or proteins, or even subdetectable levels of virus, could promote a persistent immune response which results in pain and other symptoms typically associated with acute infections. 22 Treatment associated chronic pain Vaccine reactions-Vaccines are designed to induce an immune response. After entering the body, antigen derived (pathogen associated) and host derived (damage associated) molecular patterns bind to pattern recognition receptors such as toll-like receptors found on circulating immune and stromal cells.…”

Fetoplacental transmission and placental response to SARS-CoV-2: Evidence from the literature

“…Additionally, Wu et al ( 45 ) reported that there was increased CD14+ macrophage infiltration, interferon-γ induced protein 10 (IP-10) and monocyte induced by gamma interferon (MIG) cytokines expression in term placenta from pregnant women recovering from COVID-19. The increased production of these types of chemokines within the local inflammatory lesions can induce a Th1-mediated antiviral immune response, leading to macrophage recruitment and activation for virus clearance ( 45 ). Another key finding was the reduction of plasma IL-12 secretion in pregnant patients who had recovered, indicating the activation of anti-inflammatory response might have already occurred during infection ( 45 ).…”

Transient Early Fine Motor Abnormalities in Infants Born to COVID-19 Mothers Are Associated With Placental Hypoxia and Ischemia

“…In the COVID-19 placentas, some studies observed elevated IL-5 levels as well as decreased IL-7 and TNF-related apoptosis-inducing ligand levels. In particular, the level of IFN-γ was higher in placentas that tested positive for both viral nucleic acids and proteins relative to placentas that tested positive only for the viral proteins ( 46 ). However, significantly higher levels of IL-2, IL-6, TNF-α, and IFN-γ were found in the pregnant women with COVID-19 infection.…”