Introduction

Fewer cases and less lethality from COVID-19 have been seen at high altitudes compared with the numbers reported at sea levels¹. Climatological and demographic factors could explain this observation^2,3. At high altitude, chronic hypoxia has resulted in the genetic adaptation of man to a reduced amount of oxygen^4-8. The association between hypoxia and a decreased expression of angiotensin-converting enzyme 2 (ACE2) is known¹. ACE2 is the main receptor of the SARSCoV-2 virus⁹. In addition, an increase in the activity and expression of ACE2 during pregnancy has been reported in experimental studies¹⁰. In Spain, the seroprevalence for SARS-CoV-2 during pregnancy has been published in 14%¹¹.

For diagnosis, viral RNA detection tests and serology tests that detect IgG/IgM antibodies are used¹².

Clinically, the majority of pregnant women are asymptomatic (87.9%)¹³, and as for pregnant women with symptoms, they have mild (86%), severe (9.3%) and critical (4.7%) illness¹⁴. The most frequent symptoms in pregnant women with SARS-CoV-2 are cough (76%) and fever (38%)¹⁵.

Complications from COVID-19 mostly occur in the third trimester, including 4.2% of patients who suffer from pneumonia¹¹. Obstetric complications are observed in 45% of cases¹⁵. Clinical findings resembling preeclampsia have been reported^16-18. Regarding the mode of delivery, 88% is via cesarean section¹⁵.

Vertical transmission during pregnancy, childbirth and the puerperium is very low, despite being SARS-CoV-2 found in the placenta, not so in cord blood or breast milk^19,20.

At present, no publications have been found that indicate the clinical behavior of COVID-19 in pregnant women adapted to altitude and chronic hypoxia.

Our objective is to describe the maternal and neonatal clinical characteristics of the first cases of women in labor seen in the highlands of Peru infected with COVID-19 and diagnosed by rapid IgM or IgM/IgG antibodies tests.

Methods

The present is a retrospective study of a series of cases of pregnant women treated in a single center located in the altitude between March 6, 2020 and June 15, 2020. It was approved by the institutional board of directors and informed consent was obtained from the pregnant women. We analyzed the clinical charts of 13 pregnant women admitted for labor in the city of Cajamarca, Peru, at 2 750 masl.

The tests used for the detection of antibodies against SARS-CoV-2 were subjected to immunochromatographic assay for the rapid, qualitative, and differential detection of IgG and IgM antibodies, with a sensitivity of 91.8% and specificity of 96.4%.

For the study, we used the CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development checklist. Statistical analysis was performed with SPSS software, version 19.0. Continuous variables were expressed directly as a range. Categorical variables were expressed as numbers (%).

Results

The 13 pregnant women in labor were attended at Simón Bolívar COVID-19 Hospital in Cajamarca, Perú, located at 2 750 masl. They came from altitudes between 2 035 and 3 502 masl. All cases were positive for SARS-CoV-2 IgM or IgM/IgG. Age ranged from 19 to 41 years, gestational age from 33 to 41 weeks. One patient (7.7%) presented mild symptoms (pharyngeal pain) and twelve (92.3%) were asymptomatic. Type of delivery was cesarean section in 8 (61.5%) cases and vaginal in 5 (38.5%). Eight (61.5%) had other pregnancy complications and five (38.5%) did not; two (15.4%) had preeclampsia, one (7.7%) of them HELLP syndrome that resulted in prematurity and fetal death. Three (23.1%) were complicated by postpartum hemorrhage due to uterine hypotonia during cesarean section, which required Hayman or B-Lynch suture. Two (15.4%) had oligohydramnios and other two (15.4%) urinary tract infection (Table 1, Figure 1). No patient required admission to intensive care unit or received specific treatment for COVID-19.

Table 1 Cities of origin, altitude and clinical characteristics 

*masl=meters above sea level; UTI=urinary tract infection; BTL=bilateral tubal ligation; CPD=cephalopelvic disproportion

Figure 1 Obstetric complications in pregnant women with IgM (+) for SARS-CoV-2 at altitude. 

Regarding the laboratory characteristics (Table 2), hemoglobin was reported between 11.1 g/dL and 16 g/dL, leucocytes between 8 720 /mL and 19 800 /mL, lymphocytes 1 188/mL to 2 814/mL, and platelets between 80 000/mL and 249 000/mL.

Table 2 Laboratory results 

All newborns had a negative rapid test for SARSCoV-2 IgM/IgG. The stillborn was not tested. All newborns were breastfed. The weights of the newborns ranged between 2 600 and 3 600 g. There were two cases of prematurity (15.4%) and one case of fetal death (7.7%) (Table 3).

Table 3 Neonatal outcome 

Discussion

92.3% of pregnant women evaluated in labor coming from altitudes between 2 035 and 3 502 masl, with positive IgM antibodies by rapid test for SARS-Cov-2 had asymptomatic or mild disease, and 61.5% suffered obstetric complications. There were 15.4% prematurity and 7.7% fetal deaths. No vertical transmission was found.

In altitude, most of the pregnant women studied had asymptomatic or mild disease, similar to studies from the USA, i.e., approximately 87%^13,14. The cesarean delivery rate was lower than worldwide, i.e. 61.5% instead of 88%¹⁵. However, the high percentage of other obstetrical complications associated to the COVID-19 virus stands out, as it surmounts to 61,5% instead of the 45% published in a systematic review¹⁵. Preeclampsia (15.4%) and uterine atony (23.0%) were the complications found. There was no vertical transmission detected by IgG/IgM in neonates, data that coincides with the report by Chen, who found no vertical transmission¹⁹.

Limitations of this study are having few cases, being retrospective, not having carried out molecular tests and having only evaluated patients during the third trimester; reasons for which the conclusions should be considered in context.

These results show that pregnant women in labor with a rapid test for SARS-CoV-2 in a highland region of Peru were generally asymptomatic or had mild disease. No vertical intrauterine transmission was found and there was a high percentage of other obstetric complications.