Covid-19 on Routine Testing In Eclampsia: A Duo Complication to Look out for in Pregnancy

Background: Coronavirus Disease 2019 (COVID-19) has been associated with adverse pregnancy outcomes including preeclampsia. COVID-19 and pre-eclampsia have overlapping clinical features therefore challenging to differentiate. Since COVID-19 is not routinely tested among pregnant women, it’s prudent to test it among patients presenting with Pre-eclampsia-Eclampsia. Case Presentation: A 23 year old female Gravida 1 Para 0 at 36 weeks and 5 days of amenorrhea presented at Mal Super Specialty Hospital as a referral in a semi-conscious state after a severe attack of tonic-clonic seizures. Detailed history from the husband was insignicant except for a persistent cough for the last 7 days. She had denied any visual changes, headaches or vaginal discharge. Physical examination revealed a tachycardia (150 bpm), elevated blood pressure (187/111 mmHg), a tachypnea (36 breaths/minute) and SPO 2 of 94% at room air. Routine COVID-19 Rapid test turned positive, and the urine dipstick was +3. Additional tests revealed a leukocytosis and elevated liver enzymes. Chest radiograph revealed prominent interstitial markings and a bedside transabdominal ultrasonography showed a live single intrauterine fetus in cephalic presentation with normal cardiac activity and movements. A diagnosis of a prime gravida with eclampsia and COVID-19 was made. She was managed with intravenous labetalol, she had already received a loading dose of IV Magnesium sulphate and we administered two maintenance doses during monitoring. Within an hour of admission, she had a spontaneous rupture of the amniotic membranes, with meconium stained liquor (grade 2), and the fetal heart rate (148 beats per minute) was reassuring. She had an uncomplicated vaginal delivery of a live male newborn. Shortly after delivery, she developed slight respiratory distress and signicant uid overload that was managed with furosemide. A COVID-19 RT-PCR came back negative for the neonate and positive for the mother. She was shifted to the COVID-19 treatment unit and contact limited with the child. She was kept on a course of tablets Ivermectin,

radiograph revealed prominent interstitial markings and a bedside transabdominal ultrasonography showed a live single intrauterine fetus in cephalic presentation with normal cardiac activity and movements. A diagnosis of a prime gravida with eclampsia and COVID-19 was made. She was managed with intravenous labetalol, she had already received a loading dose of IV Magnesium sulphate and we administered two maintenance doses during monitoring. Within an hour of admission, she had a spontaneous rupture of the amniotic membranes, with meconium stained liquor (grade 2), and the fetal heart rate (148 beats per minute) was reassuring. She had an uncomplicated vaginal delivery of a live male newborn. Shortly after delivery, she developed slight respiratory distress and signi cant uid overload that was managed with furosemide. A COVID-19 RT-PCR came back negative for the neonate and positive for the mother. She was shifted to the COVID-19 treatment unit and contact limited with the child. She was kept on a course of tablets Ivermectin, zinc, vitamin C, a montelukast, azithromycin, metronidazole and injectable pantoprazole. They were discharged on day 15 after recovery with a negative COVID nasopharyngeal swab.
Conclusion: A diagnosis of pre-eclampsia-Eclampsia should prompt testing for COVID-19.

Background
Coronavirus Disease 2019 (COVID-19), an infection caused by SARS-CoV-2 was initially not attributed to serious maternal or neonatal morbidities [1,2]. However, with the evolving literature, it has been reported to increase the risk for adverse pregnancy outcomes, causing higher rates of preterm birth, preeclampsia, cesarean delivery, and perinatal death especially among women with severe disease [3,4]. COVID-19 is primarily a respiratory infection that also causes signi cant vascular changes through direct endothelial damage leading to hypertension, renal diseases and affecting multiple organs just like preeclampsia in pregnancy [5]. The overlap in clinical features of COVID-19 and pre-eclampsia presents a challenge in differentiating them [6]. Mendoza and colleagues, have coined a concept of Pre-eclampsia-like syndrome associated with severe COVID-19, which could be distinguished from actual Preeclampsia by raised soluble fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) ratio, Lactate Dehydrogenase (LDH) and uterine artery pulsatility index (UtAPI) [6] although these tests may not be readily available in many hospital settings. However, Papageorghiou et al demonstrate that vascular changes that occur in preeclampsia just like in essential hypertension predispose to susceptibility to contracting COVID-19 [4].
The interplay between the two conditions remains an area of interest for further research. Therefore as we get to clearly understand the relationship, precautions for hypertensive disorders of pregnancy like Preeclampsia should be undertaken while monitoring pregnant women with COVID-19 infection [7].
Furthermore, although COVID-19 is also not routinely tested among pregnant women in most countries, it's prudent to rule it out among differentials in women presenting with Pre-eclampsia-Eclampsia clinical spectrum. In this case study we present a prime gravida who was referred to our hospital with features of eclampsia that as well turned out to be COVID-19 positive.

Case Presentation
A 23 year old female Gravida 1 Para 0 at 36 weeks and 5 days of amenorrhea presented to the emergency department of Mal Super Specialty Hospital on 2nd June 2021 as a referral from another facility in a semi-conscious state due to a severe attack of tonic-clonic seizures. A detailed history taken from the husband was insigni cant except for a persistent cough for the last 7 days. She denied any visual changes, headaches or vaginal discharge. In the Emergency department her physical examination revealed a tachycardia of 150 beats per minute(bpm), elevated blood pressure of 187/111 mmHg, a tachypnea of 36 breaths per minute and oxygen saturation of 94% at room air. Routine COVID-19 Rapid Antigen Test (RAT) turned positive, and the urine dipstick was +3. Her blood was sent for additional laboratory tests (Table 1) and a chest X-ray was ordered ( Figure 1). A diagnosis of COVID-19 in eclampsia was made. Chest radiography images revealed prominent interstitial markings and a bedside transabdominal ultrasonography revealed a live single intrauterine fetus in cephalic presentation with normal cardiac activity and movements.
On admission, she was promptly started on intravenous (IV) labetalol 20 mg that was repeated for one more dose after 15 minutes to control the blood pressure. She had been given a loading dose of IV Magnesium sulphate (MgSO4) 4g of 20% at 8:30 am from the referring facility for suspected eclampsia and the maintenance doses of 5 gm of 50% MgSO4 were administered at 12:30pm and 4:30 pm while monitoring for toxicity with patellar re exes and respiratory rate prior to each dose at Mal Superspeciality Hospital. She was shifted to the critical care unit (CCU) and monitored. Within an hour of admission, she had a spontaneous rupture of the amniotic membranes, with meconium stained liquor (grade 2); however, the fetal heart of 148 beats per minute was reassuring. The cervix dilated progressively up to 10cm leading to an uncomplicated vaginal delivery of a healthy, live born male neonate. Shortly after delivery, she developed slight respiratory distress and her renal function (renal function tests in Table 1) worsened suddenly resulting in signi cant volume overload and acute kidney injury. However, diuresis with furosemide 40 mg IV was administered on the evening of the delivery and followed up with the same dose after 12 hours, resulting in stabilization of her serum creatinine levels at 1.0 mg/dL as the hypoxic condition improved A COVID-19 Reverse ranscription polymerase chain reaction (RT-PCR) came back negative for the neonate while that of the mother returned positive the next day and she was shifted to the COVID-19 High Dependency Unit (HDU). Due to her COVID 19 positive state, contact between mother and child was limited. During her entire stay at the COVID HDU, she was kept on a course of tablets (tab) Ivermectin (once daily for 5 days),tab zinc (once a day), tab vitamin C (once daily), tab montelukast (once a day for 7 days), antibiotics: ceftriaxone IV (for 5 days) and azithromycin 500 (for 7 days) each once daily, paracetamol 100 mg IV after delivery followed by tab paracetamol 650 3 times a day, metronidazole 400 3 times a day, and inj pantoprazole 40 mg IV for 3 days followed by tab pantoprazole 40 mg orally twice daily. Mother and infant were discharged on day 15 after undergoing complete recovery and a negative COVID nasopharyngeal swab.

Discussion
Eclampsia is de ned as a seizure that occurs after 20 weeks gestation in the absence of epilepsy and other basic disorders. 80% of eclampsia cases arise during the prenatal period and childbirth although eclampsia has emerged in the postpartum period in a few cases. Even though pre-eclampsia (PE) and eclampsia do not always occur in succession, it was found that 79% cases of PE developed into eclampsia. It has been found that these patients can have symptoms of brain edema (visual symptoms, headache) even when blood pressure remains normal [8]. The exact mechanism of seizure in eclampsia is not very clear, but is most likely secondary to a combination of cerebral edema, ischemia, and transitory vasospasm of the cerebral vasculature [9].
The co-existence of COVID-19 and preeclampsia or eclampsia synergistically increases the risks of adverse pregnancy outcomes like for preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes [4]. During pregnancy, the angiotensin converting enzyme 2 (ACE2) receptor that mediates SARS-CoV-2 actions in COVID-19 is abundantly expressed in the placental tissue and plays a vital role in the regulation of arterial pressure which is disrupted leading to vasoconstriction and preeclampsia [5,10] The relationship between COVID-19 and preeclampsia-eclampsia spectrum could be looked at from different angles; COVID-19 can manifest signs and symptoms that ful ll the diagnostic criteria for preeclampsia, alternatively COVID-19 could be on an etiologic road toward preeclampsia, and as well preeclampsia can create a milieu that increases the risk of contracting COVID-19 [4]. Papageorghiou et al from a longitudinal prospective study showed that COVID-19 in pregnancy is independently associated with preeclampsia especially among nulliparous women irrespective of severity of symptoms. Furthermore, they report that prevalence of COVID-19 was highest within 33 to 37 weeks of gestation when preeclampsia typically manifests clinically [4]. In our case study the patient was nulliparous in the 36th week of gestation which reinforces these ndings.
Existing literature has indicated that there is little risk of vertical transmission of COVID-19 to the fetus [11]. In a case series of pregnant women with COVID-19, only one newborn tested positive for SARS-CoV-2 within the rst 24 h of life using a nasopharyngeal swab test [12]. In our case report, the neonate tested negative for COVID-19 in consonance with most studies that have reported no vertical transmission of SARS-CoV-2. .
At present there are no de nite guidelines for early detection or prevention of late onset postpartum eclampsia in a patient without prior eclampsia [13]. Managing hypertension and preventing convulsions are key elements in treating severe preeclampsia/eclampsia. While any of several anti-hypertensive drugs may be used to treat severe preeclampsia/eclampsia, MgSO4 is the clear drug of choice to prevent convulsions, and its potential impact on maternal morbidity and mortality is considerable [14]. In Kano, Nigeria, for example, the case fatality rate for severe preeclampsia/eclampsia fell from 20.9-2.3% after MgSO4 was introduced; perinatal mortality also fell signi cantly [15]. Although there is a theoretical concern that treatment with magnesium sulphate could worsen SARS-CoV-2 infection given the possibility of its respiratory depression, Joudi and colleagues safely administered magnesium sulphate with an intravenous loading dose of 4g and maintenance doses just like in our case study without adversities. [16]

Declarations
Ethics approval and consent to participate Informed consent was obtained from the participant included in the study. The Biomedical Ethics Research Committee issued that approval was not applicable.

Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor in-Chief of this journal.

Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current case report

Competing interests
The authors declare that they have no competing interests.

Funding
This case report was not funded.
Authors' contributions AK and SD: case design, case presentation and manuscript writing. AMK: manuscript writing, editing and proof reading. PK: case design, manuscript writing. All authors read and approved the nal manuscript. Chest X-Ray showing prominent interstitial markings