Clinical, Laboratory Characteristics and Pregnancy Outcome of COVID-19 Patients Admitted in the Largest COVID Dedicated Hospital of Bangladesh

Background: The 2019 novel corona virus (SARS-CoV-2) has become pandemic, it is of paramount importance to conduct near-real-time surveillance of women who are hospitalized and test positive for COVID-19 during pregnancy. Objective: The purpose of the present study was to evaluate clinical and laboratory characteristics and pregnancy outcome among COVID-19 patients. Methodology: This was a prospective longitudinal study done in COVID dedicated unit of Dhaka Medical College Hospital. All pregnant women admitted with confirmed COVID-19 were included. Result: Among 68 pregnant COVID patients mean (SD) age was 26.58 (4.30) years where gestational age was 25.90 (5.34) weeks. Most common symptoms were fever (94%), cough (79%), sore throat (59%), shortness of breath (44), myalgia (34%). According to severity assessment, 51 (75%) was found to be mild, moderate 9 (13%) and severe 8 (12%) respectively. Regarding overall maternal outcome among 68 patients 64 (94%) recovered and discharged, 2 (3%) of them recovered but abortion occurred and 2 (3%) died. Mean (SD) gestational age during delivery was 37.8 (1.2) weeks. Vaginal delivery was done in 18 (35%), cesarean section in 33 (65%) and 13 (19%) continuing pregnancy. Among fifty one neonate, only 41 (80%) completed RT-PCR test and found negative. Regarding neonatal outcome, 48 (94.2%) term baby, 3 (5.8%) preterm, neonatal pneumonia 1 (1%), neonatal hyperbilirubinemia 3 (6%) were observed. Conclusion: The SARS-CoV-2 infection during pregnancy might not associate with adverse obstetrical and neonatal outcomes. It appears to be unlikely of perinatal transmission of SARS-CoV-2.


Introduction
The 2019 novel corona virus (SARS-CoV-2) has become pandemic, first reported from Wuhan City of Hubei Province of China [1]. Transmission can occur through respiratory droplets from coughing and sneezing, however, aerosol transmission is also possible [2]. Clinical spectrum of COVID-19 varies from asymptomatic or symptomatic forms to clinical conditions like respiratory failure and multiple organ dysfunction syndromes (MODS) [3]. Most common clinical manifestations are fever, fatigue, cough and expectoration. Other symptoms were myalgia, anorexia, chest tightness, shortness of breath, nausea and vomiting, diarrhea, headache, and abdominal pain [4]. There are numerous differences with significant correlation in laboratory findings including neutrophil and lymphocyte count, as well as levels of plasma glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), D-dimer, erythrocyte sedimentation rate (ESR), C Reactive protein (CRP), Ferritin and procalcitonin (PCT) [5]. However, during pregnancy changes occurs in respiratory, endocrine, cardiovascular system due to changes in hormones and physiological structure [6]. Moreover, cell mediated immunity is suppressed, that might make pregnant women more prone to critical illness after infected with the virus [7]. It is of paramount importance to know about clinical characteristics, biochemical, radiological pictures of COVID-19 and outcome among pregnant patients that might help in management especially in a resource limited country like Bangladesh. So, we conducted this study.

Methodology
A prospective longitudinal study was done in COVID-19 dedicated unit of Dhaka Medical College Hospital from March 15, 2020 to August 15, 2020. All pregnant women admitted with symptoms suggestive of COVID-19 followed by confirmation with RT-PCR for SARS-CoV-2 were included. For case definitions and clinical severity assessment WHO [8] and National Guideline of Bangladesh for COVID-19 [9] were followed. Consecutive and purposive sampling techniques were used. Maternal outcome were defined by presence of sepsis, severe pneumonia, abortion, preterm labor, preeclampsia, GDM (Gestational Diabetes Mellitus), post or ante partum hemorrhage and death. However, neonatal outcome were assessed by birth weight, congenital anomaly, birth asphyxia, neonatal pneumonia, diarrhea, hyperbilirubinemia and hypoglycemia. Vital parameters with oxygen saturation were checked regularly. Laboratory investigations like Complete blood count, CRP (C-Reactive Protein), Ferritin, RBS (Random Blood Sugar), Creatinine, ALT (Alanine Transaminase), APTT (Activated Partial Thromboplastin Time), D-dimer, electrolyte, CT scan chest (if possible) and ECG were done. Ultra sonogram of pregnancy profile with anomaly scan performed after one month of discharge to assess congenital anomaly, intrauterine growth retardation (IUGR). Majority of the neonate had done with RT-PCR for SARS-CoV-2 (nasopharynx) test within 24 hours of delivery. Regular follow up was done by social media like messenger or what's app video session every one month later after discharge up to delivery. Data were analyzed by SPSS 23 version. Measurement data of normal distribution was expressed as mean±standard deviation. All counts and measurement data were descriptive statistics, and the results were expressed as mean, median &percentages. Chi square χ2 was used for categorical variables. Informed consent and ethical approval were taken accordingly (Protocol number-MEU-DMC/ECC/2020/21).

Discussion
In this prospective cohort study, 68 pregnant COVID-19 patients were admitted at COVID unit of Dhaka Medical College Hospital. Majority of them were residing in urban area and 30 (44%) had positive history of contact with suspected or confirmed COVID-19 patients. Mean gestational age on admission was 26 (5.34) weeks, Median duration of symptoms were 7 days (range 5-10) where symptomatic improvement required 18 days (range 13-21) from onset of disease. In our study, most common symptoms were fever, cough, sore throat, shortness of breath, myalgia, diarrhea, vomiting, anosmia that were very much similar with Zhang L, et al. [10] & Huang C, Wang Y, Li X, et al. [11]. Majority (75%) of pregnant women had mild symptoms with stable respiratory function where only 25% had moderate to severe symptoms evidenced by presence of hypoxia, tachypnea, hypotension with derangement of blood and biochemical markers, similar to Zaigham M, Andersson [12] but different from San-Juana R et al. [13], described only 40% had mild disease. In this study, 47 patients terminated pregnancy at 3rd trimester and the gestational age was ranging from 36 to 39 weeks. Abortion occurred in two cases around 13+ weeks. 33 cases were terminated by cesarean section, only few of those due to preterm labor, severe preeclampsia, fetal distress, history of previous cesarean section, severe COVID-19 and mostly patients own interest. Zhang L, et al. [10] described similar findings but sample size and gestational age at delivery was different. One of the reasons of behind increased caesarean section at 37+ weeksmay be due to social and psychosocial factors related to COVID-19. Patients who undergone vaginal delivery had mild disease and improved early but those had cesarean delivery took more days to recovery; three of them admitted to ICU and recovered eventually. In a single center study in Spain, Martínez-Perez O, Vouga M, Cruz Melguizo S, et al [14] described similarly though sample size was different. Under strict isolation and active treatment, majority 64 (94%) patients had been recovered and discharged. However, two patients died, both of them had severe COVID-19 (Sepsis & ARDS) with chronic disease like heart failure with chronic rheumatic heart disease and systemic lupus erythematosus (SLE). Patient who had heart failure was not under regular treatment and patient who had SLE lost to follow up for last 6 months. These factors may be the contributing factor along with COVID-19 for their severity and death. Spontaneous abortion occurred in two patients who were primi with a gestational age around 15-17 weeks whom don't have any co-morbidity. Still we don't know whether it was due to COVID-19, Zhang L, et al [10] had also observed that but could not make any conclusive comments regarding COVID-19 in relation to abortion.
Regarding blood picture showed Neutrophilia, Ferritin, APTT and D-dimer all were raised in variable percentage in our study, similar findings observed by Zhang L, et al. [10], Zaigham M, Andersson [13] and Vlachodimitropoulou Koumoutsea E et al. [15]. Only 13 patients in this study undergone HRCT chest scan, had typical HRCT manifestations like multiple flaky, patchy, segmental ground glass shadows in one or both lungs, mainly distributed outside the band similar to the findings mentioned by Lei

Limitations
However, we do have certain limitations like lack of sufficient information on newborns to determine vertical transmission, sample size was small and lack of association between cesarean delivery and risk of ICU admission.

Conclusion
In conclusion, in our study adverse outcome due to SARS-CoV-2 infection during pregnancy has been observed in very few patients. It appears to be unlikely of perinatal transmission of SARS-CoV-2, however, large scale studies with adequate samples are needed to rule out the potential risk of vertical transmission of SARS-CoV-2 and adverse pregnancy outcome.

Declaration of Conflict of Interest
All the authors do not have any possible conflicts of interest.