High case fatality rate maternal with COVID-19: lesson learned from tertiary hospital

in Indonesia

Introduction

Coronavirus disease 2019 (COVID-19) was firstly reported in Wuhan, China in

December 2019. This infectious disease caused by a novel positive – sense RNA belongs to

Betacoronavirus genus, named as severe acute respiratory syndrome coronavirus-2 (SARS-

CoV-2).  COVID-19 has spread widely around the world, therefore The World Health

Organization (WHO) announced this outbreak as a pandemic. The latest data reported by

WHO on May 1 , 2021, there have been 150,989,419 confirmed cases of COVID-19,
st

including 3,173,576 deaths globally. In addition, South – east Asia has 21,847,392 COVID-

19 confirmed cases with 272,453 death cases.  Meanwhile, Indonesia reported 1,672,880

confirmed cases with 45,652 death cases. This pandemic has become a public health threat to

people around the world presently because of unpredictability of disease progression and high

transmission potential.1, 2, 3, 4

Pregnant women are one of the high risk populations to be infected by Sars-Cov-2

virus. Sars Cov-2 infection in pregnancy is now known to result in a spectrum of

asymptomatic to critical maternal disease. Evidence is accumulating that pregnant patients

with SARS-COV-2 infection are at higher risk of hospitalization, mechanical ventilation,

intensive care unit (ICU) admission and preterm birth. A report from CDC found an

increased risk of mortality among pregnant women versus non pregnant women with SARS-

Cov-2 infection.5

Moreover, a systematic review and meta-analysis of coronavirus infection outcome

during pregnancy reported a higher rate of miscarriage, pre-term birth, pre-eclampsia,

caesarean births, and perinatal death in the setting of COVID-19 diseases. In addition,

physiologic maternal adaptation to pregnancy predisposes pregnant women to a more severe

course of pneumonia, with subsequent higher maternal and fetal morbidity and mortality.

Thus, pregnant women with COVID-19 infection need more supervision to the development

of the disease.6,7

However, the study of COVID-19 in pregnant women is limited especially in low

resources countries. Therefore, we propose a study to evaluate maternal and perinatal

outcomes on pregnant women with COVID-19 in Kariadi Hospital as tertiary hospital in

Central Java, Indonesia.

Method

This study was a single center observational study with a cross sectional method of

pregnant women suspected or confirmed COVID-19. It was performed in Kariadi hospital as

tertiary hospital in Central Java, Indonesia from March 2020 to January 2021.

The data collected were COVID-19 status, pregnancy age, symptoms of the disease,

blood test result, chest x ray result, mode of delivery, maternal, perinatal and neonatal

outcome. Confirmed COVID 19 case defined by a positive result on a reverse transcriptase-

polymerase chain reaction (RT- PCR) assay for SARS-CoV-2.

Asymptomatic cases were defined for those who reported in healthy condition with no

sign or symptoms of COVID 19. Mild cases were defined as symptoms requiring no

additional oxygen supplementation during standard labor and delivery care. Severe cases

were defined as dyspnea with respiratory rate equal or higher than 30 times per minutes,

oxygen saturation equal or less than 93% room air, or a finding of pneumonia in chest x ray,

or combination of them. Critical case was defined as any or all of the following: respiratory
failure (need for intubation on invasive ventilation), septic shock, and multiple organ

dysfunction or failure.     

Result

Sample Characteristics

In this study, we included 269 cases of confirmed and suspected COVID-19 patients

came to Kariadi Hospital, Semarang during March 2020 to January 2021, with complete data.

Among all the cases, 153 (56.9%) cases were confirmed COVID 19 which had positive result

of RT PCR test of Sars-Cov-2. The rate of pregnancy age was 37.87 weeks. The most sample

was in the third trimester (97.5%). Diabetes in pregnancy and HIV were the most common

comorbidities found in this study, there were patients came with preeclampsia, SLE and

thyroid disease.

Cough and dyspnea were the most common symptoms found in the patients,

accounting for 11,2 % and 9,3% respectively. The other symptoms were fever, fatigue, sore

throat, nasal congestion and diarrhea.  In this study, we found more symptoms in confirmed

than suspected COVID-19 patients. Symptoms such as sore throat, nasal congestion and

diarrhea were not found in suspected COVID 19 patients. Cough, fatigue and dyspnea were

statistically significant found in confirmed COVID-19 compared with suspected COVID-19

patients at admission ( p= 0.015, p= 0.028 and p= 0.043  respectively)

Based on disease severity, most of the patients were asymptomatic (74%). Disease

severity was higher in confirmed COVID 19 patients compared with non-COVID-19 and

showed a significant value (p= 0.04). 

 In the blood test profile, the rate of lymphocyte count was 13.79, it was indicated as

lymphophenia. The rates of lymphopenia, NLR, CRP,  Procalcitonin were not different

statistically between the two groups (p = 0.532, p = 0.766, p=0.208, p=0.157 respectively )

The chest x-ray test revealed 112 (41.6%) cases of pneumonia and 26 (9.7%) non

pneumonia. Abnormal chest x-ray findings in COVID-19 group had significantly higher rates

of pneumonia (p= 0.038), non-pneumonia pattern on x-ray was found higher in suspected

COVID 19 patients (p< 0.001)     

Tabel 1. Subject Characteristic and Symptoms of COVID 19

COVID 19 Status
Confirmed Suspected
Variable P
n (%) Mean (min – n (%) Mean (min-
max) max)
Gestational Age 38.7 (13.43 – 38.4 (22-42) 0.733
2nd Trimester 41.86) 0.541
3rd Trimester 4 (2.7%) 2 (2%)
124 (97.3%) 96 (98%)
Symptoms
Fever 9 (5.9%) 2 (1.7%) 0.078
Cough 23 (15%) 7(6%) 0.015
Dyspnea 19 (12.4%) 6 (5.2%) 0.043
Fatigue 9 (5.9%) 1 (0.9%) 0.028
Sore Throat 4 (2.6%) 0 (0%) 0.103
Nasal 5 (2.3%) 0(0%) 0.058
Congestion
Diarrhea 1 (0.7%) 0 (0%) 0.569
Lymphocyte 14,03 ± 6,86 13,35 ± 5,39 0.532
NLR 5 (1.87 – 48.5) 5.2 (2.2 – 31.3) 0.766
CRP 1.04 (0.08 – 1.61 (0.06 – 0.208
27.75) 260)
Procalcitonin 0.09 (0.01- 0.06 (0.01 – 0.157
11.62) 0.89)
Pneumonia 72 (47.1 %) 40 (34.5%) 0.038
Non-Pneumonia 5 (3.3%) 21(18.1%) <0.001
Gestational age 0.249
on delivery
Term
Preterm 65 (47.8%) 49 (55.7%)
71 (52.2%) 39 (44.3%)
Covid-19 0.040
Severity
Asymptomatic 107 (69.9%) 92 (82.9%)
Mild 29 (19%) 16 (14.4%)
Moderate 10 (6.5%) 1 (0.9%)
Severe 3 (2%) 2 (1.8%)
Critical 4 (2.6%) 0 (0%)

Maternal and Perinatal Outcome

The delivery mode of the patients was 69.1% caesarian section and 30.9% vaginal

delivery. Caesarian section was found higher in confirmed COVID 19 patients, incontrast

with pervaginam delivery mode. This comparison was statistically significant (p =0.02).

There were total of 12 patient sent to intensive care unit (ICU) and 11 of them needed

mechanical ventilator. Complication mostly were acute respiratory distress syndrome

(83.3%) and coagulopathy COVID-19 (83.3%). In this study, we reported 30 (11.2%)

patients died during the treatment, while 88.8% recovered. The total 26/30 (86.7%) of

maternal mortalities were COVID 19 positive which means maternal death had significantly

higher rates in COVID-19 group ( p <0.001) than non-COVID group.

There were some adverse pregnancy outcomes, 25 patients got preeclampsia, and 11

patients experienced preterm premature rupture of membrane.  In this study, we reported

some adverse perinatal outcomes as well. There were total of five babies with intrauterine

growth restriction (IUGR) and eight fetal distress and 11 cases of Intrauterine Fetal Death

(IUFD) in both groups. IUGR, fetal distress, and IUFD were found higher in COVID-19

group even though not statistically significant.

Table 2. Maternal and Perinatal Outcome

Variable COVID 19 Status P

Confirmed Suspected
n (%) Mean (min – n (%) Mean (min-max)
 max)
Delivery mode 0.029
Vaginal
Caesarean 39 (25.5%) 44 (37.9%)
114 (74.5%) 72 (62.1%)
Ongoing 0 (0%) 1 (0.9%) 0.431
Pregnancy
IUGR 4 (2.6%) 1 (0.9%) 0.283
PE 13 (8.5%) 12 (10.3%) 0.605
PPROM 4 (2.6%) 7 (6%) 0.138
Fetal distress 6 (3.9%) 2 (1.7%) 0.250
IUFD 6 (3.9%) 5 (4.4%) 0.554
ICU admission 9 (5.9%) 3 (2.6%) 0.195
Mechanical 8 (5.2%) 3 (2.6%) 0.222
Ventilator

Table 3. Maternal Mortality

COVID 19 Status Maternal Outcome P

Recovery Death
Confirmed 145 (94.7%) 8 (5.3%) <0.001
Negative result 112 (46.9%) 4 (13.3%)

The rate of birth weight was 2921 grams. The total of 41 newborn babies had low

birth weight, higher low birth weight babies found in COVID-19 group (26 babies, 17 %),

than non-COVID-19 group (15 babies, 12.9 %), although not statistically significant. The

assessment of APGAR score < 7 in the 1 minutes and 5 minutes found in 18 and 12 patients
st th

respectively in both group, but APGAR score lower than 7 in 1 minute, was found more (15

babies, 9.8 %) in COVID-19 group than non-COVID-19 group (3 babies, 2.6 %) and

statistically significant (p=0.019).

There were 19 newborns needed treatment in neonatal intensive care unit. The

mortality cases of the new born baby was 3.7%. Moreover, perinatal death was higher in

COVID-19 group (90%) than non-COVID-19 group which showed significant analysis (p=

0.028)

Table 4. Neonatal Outcome

 COVID 19 Status
Variable Confirmed Suspected P
n (%) Mean (min – max) n (%) Mean (min-max)
Neonatal 2945 (900 – 4760) 3100 (900 – 4060) 0.085
weight
LBW 26 (17%) 15 (12.9%) 0.359
APGAR 1 9 (0-9) 9 (4-9) 0.248
minutes
APGAR < 7 15 3 (2.6%) 0.019
in 1st minutes (9.8%)
APGAR 5 10 (0-10) 10 (5-10) 0.021
minutes
APGAR <7 in 10 2 (1.7%) 0.058
5th minutes (6.5%)
NICU 13 6 (5.2%) 0.292
admission (8.5%)

Table 5. Neonatal Mortality

COVID 19 Status Neonatal Mortality P

Yes No
Confirmed 9 (90%) 144 (55.6%) <0.028
Negative result 1 (10%) 115 (44.4%)

Discussion

Pregnant women are one of the vulnerable populations in this COVID-19 pandemic.

Some reports revealed this population seems to have a higher risk of mortality compared to

non-pregnant population. Moreover, pregnant patients with COVID-19 infection lead to

adverse maternal and perinatal complication. 8 In this study we reported 153/ 269 pregnant

patients, who were diagnosed as COVID-19 positive. We found 12 maternal mortalities with

case fatality rate 6.9%. Meanwhile, some study showed a low case fatality of COVID 19

infection. Prospective cohort study in New York city and Italy reported no maternal death

during the study.6,9,10

 In this study, 97.5% sample was in the third trimester. We also reported 74% of the

sample was asymptomatic infection, and only 1.9% and 1.5% were severe and critical cases,

respectively. An article review shows that evidence about the possible impact of COVID 19

in early pregnancy is limited. The majority case was in the third trimester with mild to

moderate symptoms. In addition, only a few patients required critical care admission. 8 This

result is similar with the previous study from Khoury et al, that shows 61.4% or majority of

pregnant woman with COVID 19 infection were asymptomatic. 6 A study from Savasi et al

reported 2/3 population of their study was in third trimester, while 84% of the sample

experienced COVID 19 symptoms.9

We reported the most common symptoms found in the pregnant patients were cough

(11.2%) and dypsneu (9.3%) in both group. Cough, dyspnea, and fatigue were higher in

COVID-19 patients and statistically significant. This finding is similar to a systematic study

performed by Juan et all that present the most common symptoms of the infection were fever,

cough, dyspnea, fatigue and myalgia.11

We also present 41.6% of pneumonia diagnosed by chest x ray examination, and it

was shown to have a significant value in the confirmed COVID-19 case. This finding is

similar to a cohort performed by Savasi et al that showed 55% of pneumonia findings in chest

x ray of COVID 19 in pregnant women. 9 The modulation of the maternal immune system

may affect the response to infection, and specifically to the Viruses. This COVID 19

infection makes an alteration of both innate and adaptive immune systems. Besides the

changes of immune response, the anatomical changes present in the respiratory system of

pregnant women as well. The changes of chest shape and elevation of diaphragm cause

changes to respiratory function. The reduction in total lung capacity and inability to clear

secretion can make pregnant women susceptible to severe respiratory infection. 8

 Caesarean birth was the most delivery mode of the pregnant women in this study, it

accounted for 69.1%. This result similar with study from Khoury et al showed that caesarean

birth was the mode of delivery for 52.4% of women with severe and 91.7% with critical

COVID-19.6 The study of Juan et all shows similar results as well, caesarean birth was 78 %

of delivery mode of the research sample. 11

Maternal adverse event in COVID-19 patient reported in this study were 8.5 % of

sample experienced preeclampsia (PE) and 2.6 % case of preterm premature rupture of

membrane (PPROM). A cohort study from Antoun et all, showed a similar result, they

reported 10.5% and 13.7% of their study population experienced PE and PPROM

respectively.12

Furthermore, this study reported some adverse perinatal outcomes as well. 2.6 % of

the fetus was IUGR and 3.9 % IUFD. This study also reported that 17 % of the newborn had

low birth weight in COVID-19 patient. This result was similar with a systematic review

which showed low birth weight and intrauterine fetal death as an adverse perinatal outcome

of COVID 19 in pregnant women. 11

The APGAR score < 7 in 1 and 5 minutes in this study reported 6.7% and 4.5%

respectively. In addition, 3.7% neonatal mortality was reported. In contrast with this study, a

cohort performed by Savasi et al and Antoun et all reported no neonatal mortality case.

However, the APGAR score in their study was higher than this study, they got a more

favorable outcome.9, 12

Conclusion

Increased risk of dying from pregnant women with COVID-19 was found in this

study, with CFR 6.9 %, as well as perinatal mortality was higher in COVID-19 group, so
indepth analysis of the potential risk factor that contribute in maternal and perinatal death of

COVID-19 infection in the setting of low resources country is urgently needed.

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