Next Article in Journal
Addressing Acute Stress among Professionals Caring for COVID-19 Patients: Lessons Learned during the First Outbreak in Spain (March–April 2020)
Previous Article in Journal
On-Match Impact and Outcomes of Scoring First in Professional European Female Football
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJERPH
Volume 18
Issue 22
10.3390/ijerph182212011
ijerph-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Is the Course of COVID-19 Different during Pregnancy? A Retrospective Comparative Study

by
Marcin Januszewski
1,
Laura Ziuzia-Januszewska
2,
Alicja A. Jakimiuk
3,
Waldemar Wierzba
1,4,
Anna Gluszko
5,
Joanna Zytynska-Daniluk
5 and
Artur J. Jakimiuk
1,6,*
1
Department of Obstetrics and Gynecology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland
2
Department of Otolaryngology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland
3
Department of Plastic Surgery, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland
4
Satellite Campus in Warsaw, University of Humanities and Economics, 01-513 Warsaw, Poland
5
Department of Neonatology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland
6
Center for Reproductive Health, Institute of Mother and Child, 01-211 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2021, 18(22), 12011; https://doi.org/10.3390/ijerph182212011
Submission received: 18 October 2021 / Revised: 12 November 2021 / Accepted: 14 November 2021 / Published: 16 November 2021
(This article belongs to the Section Women's Health)
Review Reports Versions Notes

Abstract

:
The COVID-19 pandemic has challenged health systems around the world. Maternal-foetal medicine, which has been particularly affected, must consider scientific data on the physiological processes occurring in the pregnant woman’s body to develop relevant standards of care. Our study retrospectively compared the clinical and laboratory characteristics of 52 COVID-19 pregnant patients with 53 controls. Most of the pregnant patients required medical attention during the third trimester and therefore we propose that vaccination is needed prior to the 30th week of pregnancy. We found no differences between the 2 groups in the course of illness classification system, days of hospital stay, need for oxygen supplementation, need for mechanical ventilation, and ICU admission. Moreover, clinical manifestations and imaging findings were comparable. Pregnant patients needed a greater oxygen flow rate and required high flow oxygen therapy more frequently. Considering pregnancy-related physiological adaptations, we found that COVID-19 infection in pregnant patients is associated with higher levels of inflammatory markers, apart from serum ferritin, than in non-pregnant women, and concluded that biomarkers of cardiac and muscle injury, as well as kidney function, may not be good predictors of COVID-19 clinical course in pregnant patients at the time of admission, but more research needs to be conducted on this topic.

1. Introduction

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by WHO on 11 March 2020, and has exposed vulnerable populations to an unprecedented global health crisis. Maternal-foetal medicine was unprepared and struggled to mount an adequate response. As new data on SARS-CoV-2 are emerging, guidelines regarding perinatal care are constantly being updated to balance evidence-based maternity care with COVID-19 management and treatment strategies.
The SARS-CoV-2 infection mainly affects the respiratory system, causing mild or moderate respiratory symptoms in 85% of cases. Cardiovascular, renal, neurological, psychiatric, dermatological, and gastrointestinal manifestations have also been reported [1,2,3,4,5]. Guan et al., [2] reported fever (88.7%), cough (67.8%), fatigue (38%), sputum production (33.7%), shortness of breath (18.7%), myalgia or arthralgia (14.9%), sore throat (13.9%), headache (13.6%), chills (11.5%), nausea or vomiting (5%), nasal congestion (4.8%), and diarrhea (3.85%) as the leading symptoms. In 5–30% of patients the virus causes severe acute respiratory syndrome (SARS) which leads to the use of mechanical ventilation methods and can progress to multiorgan failure [1,2,3]. Acute respiratory distress syndrome (ARDS) is represented by hypoxemic respiratory failure with bilateral lung infiltrates. Almost 5% of patients with COVID-19 develop a severe form of the disorder that requires treatment in an intensive care unit (ICU) [6,7,8]. The frequency of progression towards greater clinical severity and the likelihood of ICU admission in COVID-19 patients is greater with increasing age, male sex, obesity, and comorbidities such as hypertension, asthma, diabetes, and cardiovascular diseases [1,2,3]. According to Lauer et al., [9] the median incubation period, the time between exposure to the virus and the appearance of symptoms, was estimated to be 5.1 days, and 97.5% of those who develop symptoms will do so within 11.5 days.
The fact that SARS-CoV-2 has the potential to spread to extrapulmonary tissues has an impact on its clinical manifestations and is based on the binding and entry mechanism into the host cell [10].
The spike (S) protein of coronaviruses enables viral entry into target cells. Entry depends on the binding of the surface unit of the S protein, S1, to a cellular receptor, the human receptor angiotensin I-converting enzyme 2 (ACE2) [11], which facilitates viral attachment to the surface of target cells. Entry requires S protein activation by cellular proteases. In this process, driven by the S2 subunit and mediated by cellular serine protease (TMPRSS2), the fusion of viral and cellular membranes occurs [12,13,14].
SARS-CoV-2 virulency includes direct viral cytopathic effect and induction of a spontaneous immune response characterized by an exaggerated production of soluble immune mediators. This phenomenon has been called a “cytokine storm”, and as a dysregulated inflammatory reaction, it is responsible for mediating tissue damage in patients with COVID-19 [15,16,17,18]. These states of constant inflammation and hypercoagulation interplay, creating an endless feedback loop [19].
Pregnancy increases the severity of respiratory tract infections such as influenza [20,21], or RSV [22], due to physiological adaptations to pregnancy, such as the higher diaphragm position that prompts a restriction in lung expansion, increased oxygen demand, and progesterone-related airway swelling [23]. Intolerance to hypoxemia predisposes women to complications associated with respiratory infections, leading to maternal and foetal mortality and morbidity [24,25].
In addition, an immunologic modulation occurs, from a pro-inflammatory state (profitable for cell clearance, angiogenesis, and foetal growth) during the first trimester, to an anti-inflammatory condition combined with skewing towards humoral immunity (favourable for foetal growth) in the second trimester, and finally reaching a second pro-inflammatory state during the third trimester (initiation of parturition) [26,27].
Pregnant women’s sensitivity to infections and the hypercoagulation state places them in a risk group for COVID-19 infection and the increased risk of pregnancy-related complications such as miscarriages, premature birth, preeclampsia, and foetal growth restriction. Pregnancy loss, especially when occurring during the first trimester in SARS-CoV-2 infected women, is probably due to placenta infection and insufficiency [28]. Higher rates of preeclampsia were observed in a study by Conde-Agudelo et al. [29]. Di Mascio D et al., and Wei SQ et al., found increased incidences of both preeclampsia and premature births in SARS-CoV-2 infected pregnancies [30,31]. Moreover, the latter study also suggested there was an association between low birth weight and the severe form of COVID-19 [31].
Moreover, serious adverse outcomes among pregnant women with previous SARS and MERS coronavirus infections have been observed, including maternal and neonatal deaths, preterm birth, and neonatal intensive care treatment [32].
The objective of our study was to compare the clinical course and laboratory findings of pregnant women during their second and third trimesters, who were infected with SARS-CoV-2, with a cohort of non-pregnant women of reproductive age with a confirmed diagnosis of COVID-19. The outcomes we measured in relation to the severity of the disease were: course of illness classification system, increased demand for oxygen supplementation, days of hospital stay, need for oxygen supplementation and high flow oxygen therapy, need for mechanical ventilation, and ICU admissions.

2. Materials and Methods

2.1. Study Population

This retrospective single-centered study was carried out in the Department of Obstetrics and Gynecology, at the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Poland. The control group was comprised of non-pregnant women of reproductive age who were randomly recruited from those designated for COVID-19 treatment in Hospital Departments. From 15 May 2020 to 26 April 2021, a total of 52 pregnant and 53 non-pregnant women with COVID-19 infection were admitted for treatment. The research was approved by the Bioethics Committee of the Central Clinical Hospital of Interior and Administration in Warsaw.

2.2. Inclusion and Exclusion Criteria

Inclusion criteria were temperature >39 °C despite the use of paracetamol, tachypnoea >30/min, SaO2 <95% on room air, oxygen requirement, or critical course of illness. The COVID-19 diagnosis was confirmed by positive RT-PCR assay performed within no more than 13 days prior to admission.
Exclusion criteria were hospital admissions for problems other than those reflecting a deteriorating condition.

2.3. Clinical Course of Illness

We divided the patients into 4 groups based on the Polish Association of Epidemiologists and Infectiologists [33] classification guidelines determined by the severity of symptoms and the results of tests. Mild (asymptomatic, or the presence of cough, fever, dyspnoea, fatigue, headache, muscle pains, nausea, vomiting, diarrhoea), moderate (clinical and radiological features of lung occupation), severe (respiratory failure, low peripheral SpO2 < 90%), or critical (ARDS, hypotensive shock, multiorgan failure, loss of consciousness).

2.4. Study Procedures

At admission, all the women underwent blood, urine, coagulation, and biochemical blood tests, as well as computed tomography (without contrast) in cases where moderate, severe, or critical forms of COVID-19 were suspected.
The following variables were analysed: patient age, weight, height, body mass index (BMI), pre-existing medical conditions (diabetes mellitus, hypertension, hypothyroidism, asthma), symptoms, physical examination results, pregnancy status, and gestational age at the initial presentation.

2.5. Statistical Analysis

Statistical analysis was performed using Statistica 13.1 statistical software (StatSoft Polska Sp. z o.o., Kraków, Poland). Mean values and standard deviations were used to describe the study groups; in case of skewed distributions the median was calculated as a measure of central tendency, and the scatter was presented using the 25th and 75th percentile of the distribution; in case of qualitative variables the data were presented as a percentage. After assessing the normality of the distributions of the explanatory variables using the Shapiro–Wilk test, a comparative analysis of each group was performed. For variables that did not meet the assumption of near normal distribution, the Mann–Whitney U test was used to compare groups; for variables that met the assumption of normal distribution, the Student’s t-test was used for comparison. In the case of qualitative variables, the chi-squared test was used to compare the frequencies of the studied characteristics in groups. Fisher’s exact test was applied when the expected number of frequencies in the chi-square test was less than 5. Differences were considered statistically significant at p < 0.05.

3. Results

The median gestational age was 30 (IQR-7) weeks ranging from 17 to 37 weeks (Table 1). The mean age of patients was 31.9 ± 4.79 years, the median weight was 77 (IQR-26) kg, the median body mass index was 28.36 (IQR-9.88) kg/m2. Patients’ characteristics are summarized in Table 2. The main clinical symptoms were dyspnoea (n = 48, 92.31%), cough (n = 47, 90.38%) fever (n = 33, 63.46%), fatigue (n = 22, 42.31%), and muscle aches (n = 22, 42.31%). Dyspnoea and cough were more frequent, and diarrhoea less frequent, in the pregnant group (Table 3). Comorbidities included diabetes (n = 9, 17.65%), hypertension (n = 5, 10.00%), asthma (n = 2, 3.85%), and hypothyroidism (n = 18, 35.29%), the latter being more common in the pregnant cohort. (Table 4). Nine (17.31%) cases were classified as a mild course of COVID-19. Moderate, severe, and critical COVID-19 accounted for 25 (48.08%), 17 (32.69%), and 1 (1.92%) cases respectively (Table 5). The median duration of hospitalization was 8 (IQR = 6, range 2–23) days. The median length of time from the onset of SARS-CoV-2 symptoms was 7 (IQR = 6, range 1–23) days. The median percentage of lung involvement on CT was 20% (IQR = 11). Forty-two (80.77%) pregnant COVID-19 patients required oxygen supplementation and 9 (17.31%) needed high-flow therapy. The median oxygen flow rate was 4 (IQR = 4.5) l/min which was significantly higher than in the non-pregnant group. ICU admission was necessary for 2 (3.85%) cases and no mechanical ventilation was needed in the pregnant group. Clinical course parameters are presented in Table 6. Six (11.5%) cases delivered, in weeks 29, 32, 35, 36, 36, and 37 of pregnancy. Comparison of the cases’ laboratory results with those of the non-pregnant group revealed higher level of leucocytes, neutrophiles, CRP, procalcitonin, IL-6, D-dimer, and fibrinogen, and significantly lower levels of hemoglobin, lymphocytes, platelets, NT pro-BNP, calcium, ferritin, creatinine, urea, magnesium, sodium, and prothrombin time in the pregnant cohort (Table 7).

4. Discussion

4.1. Patients’ Characteristics and Comorbidities

Mean gestational age at admittance was 30 weeks. Based on current knowledge, a severe and critical COVID-19 course of illness is mainly a hyperinflammatory, immune-mediated disorder, triggered by a viral infection. As a result of their immunological features, pregnant women are supposed to be particularly susceptible to intracellular infections as well as immunological disturbances, especially during the late second and third trimesters [27]. During the second trimester, these changes are characterized mostly by the elevation of humoral immune responses and suppression of cell-mediated immunity, referred to as the T-helper lymphocyte type 1-type 2 (Th1-Th2) shift [34,35]. Therefore, Th1 cell-mediated immunity is compromised, increasing the susceptibility of pregnant women to viral and intracellular bacterial infections [26,27,36]. During the third trimester, increased numbers of monocytes and granulocytes are found in maternal blood, compared to non-pregnant women, releasing inflammatory cytokines, e.g., IL-8, TNF-a, and IL-6 [27,37,38]. Moreover, pathophysiological processes responsible for the development of hypertension, diabetes, or cardiovascular diseases intensify during the 3rd trimester and pregnant women with comorbidities and older pregnant women appear to be at particularly elevated risk of adverse maternal outcomes [23,39,40,41,42]. We believe that this should addressed by implementing preventive measures in the form of vaccination prior to week 30 of pregnancy. The use of mRNA vaccines for both maternal and foetal benefits is well established in the literature. The efficiency and safety of inoculation against SARS-CoV-2 in pregnant and lactating cohorts were underlined in studies by Collier et al., and Gray et al. [43,44]. Antibodies detected in umbilical blood and milk suggests the possibility of infant protection and their cord blood titers show a correlation with the time from vaccination to delivery [45]. Data show the presence of foetal antibodies after 15 days of both mRNA vaccine and infection. [46] However, impaired placental transmission during the third trimester has been recorded [46,47]. Therefore, late second trimester may be proposed as a perfect time for vaccination [48], although further evaluation of this is needed.
Hypothyroidism was the only comorbidity that was statistically more frequent in the pregnant group. Thyroid hormone dysfunction could affect maternal COVID-19 outcomes and increase mortality in patients with a critical illness [49,50,51]. Moreover, in a retrospective study of hospitalized moderate-to-critical COVID-19 patients, 56% of the 50 subjects studied showed lower-than-normal TSH values during their infection [52]; it has been suggested that it is necessary to monitor thyroid hormones in COVID-19 patients [53]. In our opinion however, serum TSH FT3 and FT4 concentrations in pregnant patients with a combination of primary hypothyroidism and levothyroxine treatment might be misinterpreted. Our two groups did not differ in terms of the time of SARS-CoV-2 onset, length of hospital stay, and lung involvement in the CT scan. In contrast, more severe disease at imaging has been documented in a cohort of pregnant patients from China [54].

4.2. Symptoms

The high prevalence of dyspnoea (n = 48, 92.31%), cough (n = 47, 90.38%), fever (n = 33, 63.46%), fatigue (n = 22, 42.31%), and muscle aches (n = 22, 42.31%), and the greater frequency of dyspnoea in pregnant group may be partially associated with the physiology of pregnancy and is consistent with the findings of Zambrano et al., [39]. Other studies among pregnant patients have revealed 73% [41] and 95% [55] were asymptomatic. Pregnant women have also been found to be more likely to be asymptomatic than non-pregnant women of reproductive age with COVID-19 [41]. However, these analyses included pregnant and recently pregnant women diagnosed as having either suspected or confirmed COVID-19 who were attending or admitted to hospital for any reason. At any given time, pregnant women account for 3% (234 million) of the world population of 7.8 billion [56] and only fraction of this cohort was tested. Therefore, it is not possible to identify with complete accuracy how many pregnant women have been affected and all pregnant persons should be monitored for development of symptoms and signs of COVID-19.

4.3. Clinical Course Comparison

Our case-control study, which included patients admitted to hospital for non-obstetric reasons with RT-PCR confirmed infection, indicated that pregnant women diagnosed with COVID-19 did not present more severe outcomes than their nonpregnant counterparts. Data emerging from the meta-analyses by Allotey et al., [41] Khali et al., [57] and Mazur-Bialy et al., [58] show that pregnant women may have an increased risk of developing severe symptoms. In meta-analysis made by Zambrano et al., [39] that included over 23,000 pregnant women and more than 386,000 nonpregnant women of reproductive age with symptomatic laboratory-confirmed SARS-CoV-2 infection, pregnant patients had a higher risk of ICU admission, receiving invasive ventilation, ECMO, and death. However, lack of information on the women’s pregnancy status and reasons for hospitalisation limits the usefulness of the study’s findings. Another meta-analysis made by Martinez-Portilla et al., [59] that compared 5183 pregnant with 175,905 nonpregnant women after propensity score-matching revealed a higher risk of death, pneumonia, and ICU admission.
Our study showed that the oxygen flow rate and the need for high-flow oxygen therapy were both higher in the pregnant group in comparison with the non-pregnant subjects. Due to a comparable lung involvement percentage in the 2 groups, the physiological adaptations during pregnancy (higher diaphragm position due to increased uterus size, increased oxygen demand, and progesterone-induced airway oedema) may play a role.

4.4. Laboratory Findings in Comparison with Non-Pregnant Group

The results of the laboratory tests performed on the pregnant group on admission comparing the inflammatory markers with those non-pregnant group revealed that the leucocyte counts, neutrophiles counts, CRP levels, procalcitonin levels, and IL-6 were higher, the exception being ferritin levels. Some findings are consistent with similar studies and may be explained by the hyper induction of the immune system caused by pregnancy and the SARS-CoV-2 infection [60]. Data from Liu et al., and Qiancheg et al., shows that an elevated leukocytes count in the blood is significantly more frequently observed among pregnant COVID-19-affected women [61,62]. Nevertheless, an analysis of the data reported by Liu et al., shows that the number of leukocytes is almost in the high normal range of values for pregnant women. Additionally, mild leukocytosis physiologically occurs in the third trimester [61,62,63]. Serum levels of ferritin were not significantly higher, probably due to the higher frequency of iron deficiency anaemia in the pregnant group [64].
In our study, the hypercoagulation state manifested in higher D-dimer and fibrinogen levels and lower prothrombin times may have been partially pregnancy-induced. Available data suggest an increased risk of venous thromboembolism (VTE) related to COVID-19 in infected pregnant patients compared with uninfected pregnant patients [65,66,67].
Our study revealed lower haemoglobin, platelets, creatinine, and urea levels typical for pregnancy resulting from hemodilution, increased renal flow rate and pregnancy-related thrombocytopaenia.
We also detected some shifts in ion levels due to the physiological changes during pregnancy, namely lower magnesium, calcium, and sodium levels.
Interestingly, we also discovered significantly lower NT-proBNP levels in the pregnant group and similarly for troponin levels. Nt-ProBNP is produced by the heart and the pregnant uterus, because of relevant cardiac volume overload in chronic heart failure. Between 8 and 28% of COVID-19 patients show evidence of cardiac injury with elevated troponin and natriuretic peptides [68,69]. Some data support NT-proBNP as an independent risk factor for in-hospital death, ICU admission, mechanical ventilation, and coagulopathy in patients with severe COVID-19 disease [70].

5. Conclusions

Most pregnant patients infected with SARS-CoV-2 require medical attention during the third trimester. We propose that all pregnant women should be vaccinated prior to the 30th week of pregnancy.
Pregnant women diagnosed with COVID-19 did not present more severe outcomes than their non-pregnant counterparts, probably due to the small patient sample and imperfect measuring methods. Clinical manifestations of COVID-19 disease were similar in the two cohorts, and some, like dyspnoea or fatigue, overlap with the symptoms of normal pregnancy.
The laboratory and imaging findings were generally similar in both the pregnant and non-pregnant groups. Laboratory results for the coagulation test, morphology, or serum levels of ions can be explained by normal pregnancy-related physiological processes. Moderate and severe COVID-19 clinical courses in pregnant women are associated with higher levels of inflammatory markers, apart from serum ferritin, than in non-pregnant women, which might be partially explained by the imposition of immunological features and iron deficiency anaemia. Biomarkers of cardiac and muscle injury, as well as kidney function, may not be good predictors of COVID-19 clinical course in pregnant patients at the time of admission, but more research needs to be conducted on this topic.

5.1. Research Implications

Future studies of pregnant patients infected with SARS-CoV-2 should focus on the assessment of disease severity predictors for early identification of patients at risk of developing complications, and thus improve optimalization and preventative efforts in this cohort. Further validation with a larger study group and risk models are needed to provide useful data for the effective management of health resources in the COVID-19 era.

5.2. Strengths and Limitations

The main strength of our study is the variety of parameters evaluated.
The main weaknesses of our investigation include its single-centre nature, as well as a small and homogeneous group of patients.

Author Contributions

Conceptualization: M.J.; methodology, M.J., A.J.J., L.Z.-J. and W.W.; software, A.A.J.; validation, M.J., A.J.J. and L.Z.-J.; investigation, M.J., A.A.J., A.G., J.Ż.-D.; data curation, M.J.; writing—original draft preparation, M.J.; writing—review and editing, A.J.J., M.J.; visualization, L.Z.-J.; supervision, A.J.J. and W.W.; project administration, W.W.; funding acquisition, A.J.J. and W.W. All authors discussed the results and reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Bioethics Committee of the Central Clinical Hospital of the Interior and Administration in Warsaw decision nr 104/21.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The datasets generated and/or analyzed during the current study are not publicly available due to our policy but are available from the corresponding author upon reasonable request.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef] [Green Version]
  2. Guan, W.-J.; Ni, Z.-Y.; Hu, Y.; Liang, W.-H.; Ou, C.-Q.; He, J.-X.; Liu, L.; Shan, H.; Lei, C.-L.; Hui, D.S.; et al. China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020, 382, 1708–1720. [Google Scholar] [CrossRef] [PubMed]
  3. Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020, 323, 1061–1069. [Google Scholar] [CrossRef] [PubMed]
  4. Grant, M.C.; Geoghegan, L.; Arbyn, M.; Mohammed, Z.; McGuinness, L.; Clarke, E.L.; Wade, R.G. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLoS ONE 2020, 15, e0234765. [Google Scholar] [CrossRef] [PubMed]
  5. Rogers, J.P.; Chesney, E.; Oliver, D.; Pollak, T.A.; McGuire, P.; Fusar-Poli, P.; Zandi, M.; Lewis, G.; David, A. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: A systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 2020, 7, 611–627. [Google Scholar] [CrossRef]
  6. Vittori, A.; Lerman, J.; Cascella, M.; Gomez-Morad, A.D.; Marchetti, G.; Marinangeli, F.; Picardo, S.G. COVID-19 pandemic acute respiratory distress syndrome survivors: Pain after the storm? Anesth. Analg. 2020, 131, 117–119. [Google Scholar] [CrossRef] [PubMed]
  7. Ñamendys-Silva, S.A. ECMO for ARDS due to COVID-19. Heart Lung 2020, 49, 348–349. [Google Scholar] [CrossRef] [Green Version]
  8. Yang, X.; Yu, Y.; Xu, J.; Shu, H.; Xia, J.; Liu, H.; Wu, Y.; Zhang, L.; Yu, Z.; Fang, M.; et al. Clinical course and outcomes of critically ill patients with SARSCoV-2 pneumonia in Wuhan, China: A singlecentered, retrospective, observational study. Lancet Respir. Med. 2020, 8, 475–481. [Google Scholar] [CrossRef] [Green Version]
  9. Lauer, S.A.; Grantz, K.H.; Bi, Q.; Jones, F.K.; Zheng, Q.; Meredith, H.R.; Azman, A.S.; Reich, N.G.; Lessler, J. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann. Intern. Med. 2020, 172, 577–582. [Google Scholar] [CrossRef] [Green Version]
  10. Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.-H.; Nitsche, A.; et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020, 181, 271–280.e8. [Google Scholar] [CrossRef]
  11. Li, W.; Moore, M.J.; Vasilieva, N.; Sui, J.; Wong, S.K.; Berne, M.A.; Somasundaran, M.; Sullivan, J.L.; Luzuriaga, K.; Greenough, T.C. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426, 450–454. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  12. Glowacka, I.; Bertram, S.; Müller, M.A.; Allen, P.; Soilleux, E.; Pfefferle, S.; Steffen, I.; Tsegaye, T.S.; He, Y.; Gnirss, K. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J. Virol. 2011, 85, 4122–4134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Matsuyama, S.; Nagata, N.; Shirato, K.; Kawase, M.; Takeda, M.; Taguchi, F. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J. Virol. 2010, 84, 12658–12664. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Hidalgo, P.; Valdés, M.; González, R.A. Molecular biology of coronaviruses: An overview of virus-host interactions and pathogenesis. Boletín Médico del Hospital Infantil de México 2021, 78, 41–58. [Google Scholar] [CrossRef] [PubMed]
  15. Conti, P.; Ronconi, G.; Caraffa, A.; Gallenga, C.E.; Ross, R.; Frydas, I.; Kritas, S.K. Induction of pro-inflammatory cytokines. (IL-1 and IL-6) and lung inflammation by Coronavirus-19. (COVI-19 or SARS-CoV-2): Anti-inflammatory strategies. J. Biol. Regul. Homeost. Agents 2020, 34, 327–331. [Google Scholar] [CrossRef]
  16. McGonagle, D.; Sharif, K.; O’Regan, A.; Bridgewood, C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun. Rev. 2020, 19, 102537. [Google Scholar] [CrossRef]
  17. Wan, S.; Yi, Q.; Fan, S.; Lv, J.; Zhang, X.; Guo, L.; Lang, C.; Xiao, Q.; Xiao, K.; Yi, Z.; et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv 2020. [Google Scholar] [CrossRef] [Green Version]
  18. Yang, Y.; Shen, C.; Li, J.; Yuan, J.; Wei, J.; Huang, F.; Wang, F.; Li, G.; Li, Y.; Xing, L.; et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J. Allergy Clin. Immunol. 2020, 146, 119–127.e4. [Google Scholar] [CrossRef]
  19. Domingo, P.; Mur, I.; Pomar, V.; Corominas, H.; Casademont, J.; de Benito, N. The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19). EBioMedicine 2020, 58, 102887. [Google Scholar] [CrossRef]
  20. Siston, A.M.; Rasmussen, S.A.; Honein, M.A.; Fry, A.M.; Seib, K.; Callaghan, W.M.; Louie, J.; Doyle, T.J.; Crockett, M.; Lynfield, R.; et al. Pandemic H1N1 Influenza in Pregnancy Working Group. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010, 303, 1517–1525. [Google Scholar] [CrossRef]
  21. Jamieson, D.J.; Honein, M.A.; Rasmussen, S.A.; Williams, J.L.; Swerdlow, D.L.; Biggerstaff, M.S.; Lindstrom, S.; Louie, J.K.; Christ, C.M.; Bohm, S.R.; et al. Novel Influenza A (H1N1) Pregnancy Working Group. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009, 374, 451–458. [Google Scholar] [CrossRef]
  22. Hause, A.M.; Panagiotakopoulos, L.; Weintraub, E.S.; Sy, L.S.; Glenn, S.C.; Tseng, H.-F.; McNeil, M.M. Adverse Outcomes in Pregnant Women Hospitalized With Respiratory Syncytial Virus Infection: A Case Series. Clin. Infect. Dis. 2021, 72, 138–140. [Google Scholar] [CrossRef]
  23. Chen, H.; Guo, J.; Wang, C.; Luo, F.; Yu, X.; Zhang, W.; Li, J.; Zhao, D.; Xu, D.; Gong, Q.; et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet 2020, 395, 809–815. [Google Scholar] [CrossRef] [Green Version]
  24. Liu, H.; Wang, L.-L.; Zhao, S.-J.; Kwak-Kim, J.; Mor, G.; Liao, A.-H. Why are pregnant women susceptible to COVID-19? An immunological viewpoint. J. Reprod. Immunol. 2020, 139, 103122. [Google Scholar] [CrossRef] [PubMed]
  25. Rasmussen, S.; Jamieson, D.J.; Uyeki, T.M. Effects of Influenza on Pregnant Women and Infants. Am. J. Obstet. Gynecol. 2012, 207, S3–S8. [Google Scholar] [CrossRef]
  26. Mor, G.; Aldo, P.; Alvero, A.B. The unique immunological and microbial aspects of pregnancy. Nat. Rev. Immunol. 2017, 17, 469–482. [Google Scholar] [CrossRef]
  27. Ferrer-Oliveras, R.; Mendoza, M.; Capote, S.; Pratcorona, L.; Esteve-Valverde, E.; Cabero-Roura, L.; Alijotas-Reig, J. Immunological and physiopathological approach of COVID-19 in pregnancy. Arch. Gynecol. Obstet. 2021, 304, 39–57. [Google Scholar] [CrossRef]
  28. Kazemi, S.N.; Hajikhani, B.; Didar, H.; Hosseini, S.S.; Haddadi, S.; Khalili, F.; Mirsaeidi, M.; Nasiri, M.J. COVID-19 and cause of pregnancy loss during the pandemic: A systematic review. PLoS ONE 2021, 16, e0255994. [Google Scholar] [CrossRef]
  29. Conde-Agudelo, A.; Romero, R. SARS-CoV-2 infection during pregnancy and risk of preeclampsia: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2021. [Google Scholar] [CrossRef]
  30. Di Mascio, D.; Khalil, A.; Saccone, G.; Rizzo, G.; Buca, D.; Liberati, M.; Vecchiet, J.; Nappi, L.; Scambia, G.; Berghella, V.; et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. MFM 2020, 2, 100107. [Google Scholar] [CrossRef]
  31. Wei, S.Q.; Bilodeau-Bertrand, M.; Liu, S.; Auger, N. The impact of COVID-19 on pregnancy outcomes: A systematic review and meta-analysis. Can. Med. Assoc. J. 2021, 193, E540–E548. [Google Scholar] [CrossRef]
  32. Schwartz, D.A.; Graham, A.L. Potential maternal and infant outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) infecting pregnant women: Lessons from SARS, MERS, and other human coronavirus infections. Viruses 2020, 12, 194. [Google Scholar] [CrossRef] [Green Version]
  33. Flisiak, R.; Horban, A.; Jaroszewicz, J.; Kozielewicz, D.; Pawłowska, M.; Parczewski, M.; Piekarska, A.; Tomasiewicz, K.; Zarębska-Michaluk, D. Management of SARS-CoV-2 infection: Recommendations of the Polish Association of Epidemiologists and Infectiologists as of March 31, 2020. Pol. Arch. Intern. Med. 2020, 130, 352–357. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Figueiro-Filho, E.A.; Yudin, M.; Farine, D. COVID-19 during pregnancy: An overview of maternal characteristics, clinical symptoms, maternal and neonatal outcomes of 10,996 cases described in 15 countries. J. Périnat. Med. 2020, 48, 900–911. [Google Scholar] [CrossRef]
  35. Littauer, E.Q.; Esser, E.S.; Antao, O.Q.; Vassilieva, E.V.; Compans, R.W.; Skountzou, I. H1N1 influenza virus infection results in adverse pregnancy outcomes by disrupting tissue-specific hormonal regulation. PLOS Pathog. 2017, 13, e1006757. [Google Scholar] [CrossRef] [Green Version]
  36. Kumpel, B.M.; Manoussaka, M.S. Placental immunology and maternal alloimmune responses. Vox Sang. 2011, 102, 2–12. [Google Scholar] [CrossRef]
  37. Messerli, M.; May, K.; Hansson, S.; Schneider, H.; Holzgreve, W.; Hahn, S.; Rusterholz, C. Feto-maternal interactions in pregnancies: Placental microparticles activate peripheral blood monocytes. Placenta 2010, 31, 106–112. [Google Scholar] [CrossRef] [PubMed]
  38. Wegmann, T.G.; Lin, H.; Guilbert, L.; Mosmann, T.R. Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon? Immunol. Today 1993, 14, 353–356. [Google Scholar] [CrossRef]
  39. Zambrano, L.D.; Ellington, S.; Strid, P.; Galang, R.R.; Oduyebo, T.; Tong, V.T.; Woodworth, K.R.; Nahabedian, J.F.; Azziz-Baumgartner, E.; Gilboa, S.M.; et al. Meaney-Delman D. CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status—United States, 22 January–3 October 2020. MMWR Morb. Mortal. Wkly. Rep. 2020, 69, 1641–1647. [Google Scholar] [CrossRef]
  40. López, M.; Gonce, A.; Meler, E.; Plaza, A.; Hernández, S.; Martinez-Portilla, R.J.; Cobo, T.; García, F.; Roig, M.D.G.; Gratacós, E.; et al. Coronavirus Disease 2019 in Pregnancy: A Clinical Management Protocol and Considerations for Practice. Fetal Diagn. Ther. 2020, 47, 519–528. [Google Scholar] [CrossRef] [PubMed]
  41. Allotey, J.; Stallings, E.; Bonet, M.; Yap, M.; Chatterjee, S.; Kew, T.; Debenham, L.; Llavall, A.C.; Dixit, A.; Zhou, D.; et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: Living systematic review and meta-analysis. BMJ 2020, 370, m3320. [Google Scholar] [CrossRef]
  42. Ellington, S.; Strid, P.; Tong, V.T.; Woodworth, K.; Galang, R.R.; Zambrano, L.D.; Nahabedian, J.; Anderson, K.; Gilboa, S.M. Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status—United States, 22 January–7 June 2020. Morb. Mortal. Wkly. Rep. 2020, 69, 769–775. [Google Scholar] [CrossRef] [PubMed]
  43. Collier, A.-R.Y.; McMahan, K.; Yu, J.; Tostanoski, L.H.; Aguayo, R.; Ansel, J.; Chandrashekar, A.; Patel, S.; Bondzie, E.A.; Sellers, D.; et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA 2021, 325, 2370. [Google Scholar] [CrossRef] [PubMed]
  44. Gray, K.J.; Bordt, E.A.; Atyeo, C.; Deriso, E.; Akinwunmi, B.; Young, N.; Baez, A.M.; Shook, L.L.; Cvrk, D.; James, K.; et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: A cohort study. Am. J. Obstet. Gynecol. 2021, 225, 303.e1–303.e17. [Google Scholar] [CrossRef]
  45. Zdanowski, W.; Waśniewski, T. Evaluation of SARS-CoV-2 Spike Protein Antibody Titers in Cord Blood after COVID-19 Vaccination during Pregnancy in Polish Healthcare Workers: Preliminary Results. Vaccines 2021, 9, 675. [Google Scholar] [CrossRef]
  46. Beharier, O.; Mayo, R.P.; Raz, T.; Sacks, K.N.; Schreiber, L.; Suissa-Cohen, Y.; Chen, R.; Gomez-Tolub, R.; Hadar, E.; Gabbay-Benziv, R.; et al. Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine. J. Clin. Investig. 2021, 131, e154834. [Google Scholar] [CrossRef]
  47. Atyeo, C.; Pullen, K.M.; Bordt, E.A.; Fischinger, S.; Burke, J.; Michell, A.; Slein, M.D.; Loos, C.; Shook, L.L.; Boatin, A.A.; et al. Compromised SARS-CoV-2-specific placental antibody transfer. Cell 2021, 184, 628–642.e10. [Google Scholar] [CrossRef]
  48. Douxfils, J.; Gillot, C.; De Gottal, É.; Vandervinne, S.; Bayart, J.-L.; Dogné, J.-M.; Favresse, J. Efficient Maternal to Neonate Transfer of Neutralizing Antibodies after SARS-CoV-2 Vaccination with BNT162b2: A Case-Report and Discussion of the Literature. Vaccines 2021, 9, 907. [Google Scholar] [CrossRef]
  49. Rothberger, G.D.; Valestra, P.K.; Knight, K.; Desai, A.K.; Calixte, R.; Shapiro, L.E. Low free T3 is associated with worse out- comes in patients in the ICU requiring invasive mechanical ventilation. J. Intensive Care Med. 2021, 36, 313–318. [Google Scholar] [CrossRef] [PubMed]
  50. Kim, J.G.; Shin, H.; Kim, W.; Lim, T.H.; Jang, B.; Cho, Y.; Choi, K.-S.; Ahn, C.; Lee, J.; Na, M.K. The value of decreased thyroid hormone for predicting mortality in adult septic patients: A systematic review and meta-analysis. Sci. Rep. 2018, 8, 14137. [Google Scholar] [CrossRef] [Green Version]
  51. Akbaş, T.; Deyneli, O.; Sönmez, F.T.; Akalın, S. The pituitary-gonadal-thyroid and lactotroph axes in critically ill patients. Endokrynol. Pol. 2016, 67, 305–312. [Google Scholar] [CrossRef] [Green Version]
  52. Chen, M.; Zhou, W.; Xu, W.-W. Thyroid Function Analysis in 50 Patients with COVID-19: A Retrospective Study. Thyroid 2021, 31, 8–11. [Google Scholar] [CrossRef] [PubMed]
  53. Speer, G.; Somogyi, P. Thyroid complications of SARS and coronavirus disease 2019 (COVID-19). Endocr. J. 2021, 68, 129–136. [Google Scholar] [CrossRef] [PubMed]
  54. Liu, F.; Liu, H.; Hou, L.; Li, J.; Zheng, H.; Chi, R.; Lan, W.; Wang, D. Clinico-Radiological Features and Outcomes in Pregnant Women with COVID-19: Compared with Age-Matched Non-Pregnant Women (3/16/2020). Available online: https://ssrn.com/abstract=3556647 (accessed on 7 May 2021).
  55. Yanes-Lane, M.; Winters, N.; Fregonese, F.; Bastos, M.; Perlman-Arrow, S.; Campbell, J.R.; Menzies, D. Proportion of asymptomatic infection among COVID-19 positive persons and their transmission potential: A systematic review and meta-analysis. PLoS ONE 2020, 15, e0241536. [Google Scholar] [CrossRef] [PubMed]
  56. Sedgh, G.; Singh, S.; Hussain, R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud. Fam. Plan. 2014, 45, 301–314. [Google Scholar] [CrossRef] [Green Version]
  57. Khalil, A.; Kalafat, E.; Benlioglu, C.; O’Brien, P.; Morris, E.; Draycott, T.; Thangaratinam, S.; Le Doare, K.; Heath, P.; Ladhani, S.; et al. SARS-Cov-2 Infection in Pregnancy: A Systematic Review and Meta-Analysis Of Clinical Features And Pregnancy Outcomes. EClinicalMedicine 2020, 25, 100446. [Google Scholar] [CrossRef]
  58. Mazur-Bialy, A.I.; Kołomańska-Bogucka, D.; Tim, S.; Opławski, M. Pregnancy and Childbirth in the COVID-19 Era-The Course of Disease and Maternal-Fetal Transmission. J. Clin. Med. 2020, 9, 3749. [Google Scholar] [CrossRef]
  59. Martinez-Portilla, R.J.; Sotiriadis, A.; Chatzakis, C.; Torres-Torres, J.; Espino YSosa, S.; Sandoval-Mandujano, K.; Castro-Bernabe, D.A.; Medina-Jimenez, V.; Monarrez-Martin, J.C.; Figueras, F.; et al. Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: Propensity score matched analysis of a nationwide prospective cohort (COV19Mx). Ultrasound Obstet. Gynecol. 2021, 57, 224–231. [Google Scholar] [CrossRef] [PubMed]
  60. Tanacan, A.; Yazihan, N.; Erol, S.A.; Anuk, A.T.; Yetiskin, F.D.Y.; Biriken, D.; Ozgu-Erdinc, A.; Keskin, H.L.; Tekin, O.M.; Sahin, D. The impact of COVID-19 infection on the cytokine profile of pregnant women: A prospective case-control study. Cytokine 2021, 140, 155431. [Google Scholar] [CrossRef]
  61. Liu, H.; Liu, F.; Li, J.; Zhang, T.; Wang, D.; Lan, W. Clinical and CT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children. J. Infect. 2020, 80, e7–e13. [Google Scholar] [CrossRef] [PubMed]
  62. Qiancheng, X.; Jian, S.; Lingling, P.; Lei, H.; Xiaogan, J.; Weihua, L.; Gang, Y.; Shirong, L.; Zhen, W.; GuoPing, X.; et al. Coronavirus disease 2019 in pregnancy. Int. J. Infect. Dis. 2020, 95, 376–383. [Google Scholar] [CrossRef]
  63. Novoa, R.H.; Quintana, W.; Llancarí, P.; Urbina-Quispe, K.; Guevara-Ríos, E.; Ventura, W. Maternal clinical characteristics and perinatal outcomes among pregnant women with coronavirus disease 2019. A systematic review. Travel Med. Infect. Dis. 2021, 39, 101919. [Google Scholar] [CrossRef]
  64. Stewart, T.; Lambourne, J.; Thorp-Jones, D.; Thomas, D. Implementation of early management of iron deficiency in pregnancy during the SARS-CoV-2 pandemic. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021, 258, 60–62. [Google Scholar] [CrossRef]
  65. Metz, T.D.; Clifton, R.G.; Hughes, B.L.; Sandoval, G.; Saade, G.R.; Grobman, W.A.; Manuck, T.A.; Miodovnik, M.; Sowles, A.; Clark, K.; et al. Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19). Obstet. Gynecol. 2021, 137, 571–580. [Google Scholar] [CrossRef]
  66. Jering, K.S.; Claggett, B.L.; Cunningham, J.W.; Rosenthal, N.; Vardeny, O.; Greene, M.F.; Solomon, S.D. Clinical Characteristics and Outcomes of Hospitalized Women Giving Birth With and Without COVID-19. JAMA Intern. Med. 2021, 181, 714–717. [Google Scholar] [CrossRef] [PubMed]
  67. Servante, J.; Swallow, G.; Thornton, J.G.; Myers, B.; Munireddy, S.; Malinowski, A.K.; Othman, M.; Li, W.; O’Donoghue, K.; Walker, K.F. Haemostatic and thrombo-embolic complications in pregnant women with COVID-19: A systematic review and critical analysis. BMC Pregnancy Childbirth 2021, 21, 108. [Google Scholar] [CrossRef]
  68. Liu, P.P.; Blet, A.; Smyth, D.; Li, H. The science underlying COVID-19: Implications for the cardiovascular system. Circulation 2020, 142, 68–78. [Google Scholar] [CrossRef] [Green Version]
  69. Bhatraju, P.K.; Ghassemieh, B.J.; Nichols, M.; Kim, R.; Jerome, K.R.; Nalla, A.K.; Greninger, A.L.; Pipavath, S.; Wurfel, M.M.; Evans, L.; et al. Covid-19 in Critically Ill Patients in the Seattle Region—Case Series. N. Engl. J. Med. 2020, 382, 2012–2022. [Google Scholar] [CrossRef] [PubMed]
  70. Bansal, A.; Kumar, A.; Patel, D.; Puri, R.; Kalra, A.; Kapadia, S.R.; Reed, G.W. Meta-analysis Comparing Outcomes in Patients with and Without Cardiac Injury and Coronavirus Disease 2019 (COVID 19). Am. J. Cardiol. 2021, 141, 140–146. [Google Scholar] [CrossRef] [PubMed]
Table
Table 1. Weeks of pregnancy.
Table 1. Weeks of pregnancy.
hbdn (%)
≤2612 (23.08)
171 (1.92)
223 (5.77)
242 (3.85)
252 (3.85)
264 (7.69)
27–3015 (28.85)
274 (7.69)
282 (3.85)
296 (11.54)
303 (5.77)
31–338 (15.38)
311 (1.92)
324 (7.69)
333 (5.77)
34–3615 (28.85)
347 (13.46)
356 (11.54)
362 (3.85)
≥372 (3.85)
372 (3.85)
Table
Table 2. Patients’ characteristics.
Table 2. Patients’ characteristics.
VariableCasesControlsp-Value
Age (years)N52530.282
Mean ± SD31.9 ± 4.7932.96 ± 5.22
Range22–4023–45
hbdN520
Median (IQR)30 (7)
Range17–37
Weight (kg)N43330.566
Median (IQR)77 (26)75 (27)
Range54–13052–120
Height (cm)N43330.415
Mean ± SD166.12 ± 5.83167.21 ± 5.69
Range151–175156–180
BMI (kg/m2)N43350.379
Median (IQR)28.36 (9.88)29.3 (7.71)
Range20.82–45.9118.59–45.17
Table
Table 3. Patients’ symptoms.
Table 3. Patients’ symptoms.
VariableCasesControlsp-Value (Pearson’s Chi-Square Test)
Fatigueno30 (57.69%)29 (54.72%)0.759 *
yes22 (42.31%)24 (45.28%)
Sputumno49 (94.23%)47 (88.68%)0.488 **
yes3 (5.77%)6 (11.32%)
Dyspnoeano4 (7.69%)16 (30.77%)0.003 *
yes48 (92.31%)36 (69.23%)
Muscle achesno30 (57.69%)31 (58.49%)0.934 *
yes22 (42.31%)22 (41.51%)
Sore throatno46 (88.46%)47 (88.68%)0.972 *
yes6 (11.54%)6 (11.32%)
Headacheno40 (76.92%)35 (66.04%)0.217 *
yes12 (23.08%)18 (33.96%)
Chillsno50 (96.15%)52 (98.11%)0.618 **
yes2 (3.85%)1 (1.89%)
Nauseano50 (96.15%)48 (90.57%)0.437 **
yes2 (3.85%)5 (9.43%)
Nasal dischargeno47 (90.38%)48 (90.57%)1 **
yes5 (9.62%)5 (9.43%)
Diarrhoeano50 (96.15%)44 (83.02%)0.028 *
yes2 (3.85%)9 (16.98%)
Smell and taste disorderno38 (73.08%)34 (64.15%)0.325 *
yes14 (26.92%)19 (35.85%)
Coughno5 (9.62%)20 (37.74%)<0.001 *
yes47 (90.38%)33 (62.26%)
Feverno19 (36.54%)19 (35.85%)0.941 *
yes33 (63.46%)34 (64.15%)
* Pearson’s chi-square test, ** Fisher’s exact test.
Table
Table 4. Patient’s comorbidities.
Table 4. Patient’s comorbidities.
VariableCasesControlsp-Value (Pearson’s Chi-Square Test)
Preeclampsiano50 (98.04%)53 (100%)0.490 **
yes1 (1.96%)0 (0%)
Hypothyroidismno33 (64.71%)44 (83.02%)0.033 *
yes18 (35.29%)9 (16.98%)
Hypertensionno45 (90.00%)43 (81.13%)0.202 *
yes5 (10.00%)10 (18.87%)
Diabetes mellitusno42 (82.35%)47 (88.68%)0.359 *
yes9 (17.65%)6 (11.32%)
Asthmano50 (96.15%)49 (92.45%)1 **
yes2 (3.85%)4 (7.55%)
* Pearson’s chi-square test, ** Fisher’s exact test.
Table
Table 5. Clinical course of illness.
Table 5. Clinical course of illness.
SeverityCasesControlsTotal
1 mild illness9 (17.31%)6 (11.32%)15
2 moderate illness25 (48.08%)32 (60.38%)57
3 severe illness17 (32.69%)14 (26.42%)31
4 critical illness1 (1.92%)1 (1.89%)2
Total5253105
Table
Table 6. Clinical course parameters.
Table 6. Clinical course parameters.
VariableCasesControlsp-Value
Length of hospitalisation (days)N52530.120
Median (IQR)8 (6)10 (5)
Range2–233–25
Percentage of lung involvement on CT (%)N34460.539
Median (IQR)20 (11)27.5 (35)
Range1–600–80
Time from the onset of SARS-CoV-2 symptoms (days)N51500.863
Median (IQR)7 (6)7.5 (6)
Range1--232–21
Oxygen flow (L/min)N52530.009
Median (IQR)4 (4.5)2 (5)
Range0–150–15
VariableCasesControlsp-Value (Pearson’s Chi-Square Test)
Need for oxygen supplementationno10 (19.23%)23 (43.40%)0.008
yes42 (80.77%)30 (56.60%)
Need for invasive ventilationno52 (100.00%)52 (98.11%)0.32
yes0 (0.00%)1 (1.89%)
Need for high-flow oxygen therapyno43 (82.69%)52 (98.11%)0.007
yes9 (17.31%)1 (1.89%)
Need for ICU admissionno50 (96.15%)52 (98.11%)0.547
Table
Table 7. Patients’ laboratory results.
Table 7. Patients’ laboratory results.
VariableCasesControlsp-Value
Hemoglobin (g/dL)N5253<0.001
Median (IQR)12 (1.1)13.3 (1.6)
Range7.3–159–16.4
Leukocytes (×103/μL)N52530.012
Median (IQR)7.7 (3.23)6.37 (3.89)
Range2.99–18.582.12–18.13
Lymphocytes (×103/μL)N52530.002
Median (IQR)0.97 (0.32)1.35 (0.92)
Range0.6–2.650.32–3.23
Neutrophils (×103/μL)N5253<0.001
Median (IQR)5.8 (3.11)4.17 (2.98)
Range2.16–16.771.21–14.89
Platelets (×103/μL)N52530.003
Median (IQR)184.5 (58.5)236 (104)
Range34–4440.32–475
AST—Aspartate aminotransferase (U/L)N52520.879
Median (IQR)28 (18.5)26.5 (26.5)
Range9–2630–211
APTT—activated partial thromboplastin time (s)N49400.318
Median (IQR)33.7 (5.5)32.45 (5.2)
Range22.2–4725.6–63.6
ALT—Alanine aminotransferase (U/L)N50520.10
Median (IQR)24 (24)25 (33.5)
Range6–1776–130
Bilirubin (mg/dL)N49400.16
Median (IQR)0.46 (0.51)0.36 (0.28)
Range0.09–1.660.14–1.81
NT pro-BNP (pg/mL)N44340.006
Median (IQR)29.5 (39)69.5 (135)
Range5–2609–1109
Calcium (mmol/L)N43180.021
Mean ± SD2.16 ± 0.092.22 ± 0.1
Range1.86–2.412.05–2.48
CK—creatine kinase (U/L)N50310.653
Median (IQR)61.5 (69)60 (62)
Range11–72915–1019
CRP—C Reactive Protein (mg/L)N5253<0.001
Median (IQR)46.95 (52.4)18 (45.5)
Range1.2–1600.3–210.4
D-dimer (μg/L FEU)N3247<0.001
Median (IQR)1178 (515.5)624 (601)
Range458–4235211–6650
Ferritin (ng/mL)N50210.001
Median (IQR)83.5 (109)222 (204)
Range13–4500–699
Fibrinogen (mg/dL)N5020<0.001
Median (IQR)553 (225)363.5 (230.5)
Range273–941186–654
Glucose (mg/dL)N41240.421
Median (IQR)92 (17)94 (33)
Range67–15772–253
Potassium (mmol/L)N52500.163
Median (IQR)3.93 (0.64)4.02 (0.63)
Range2.95–4.963.33–4.57
Creatinine (mg/dL)N5050<0.001
Median (IQR)0.52 (0.17)0.74 (0.18)
Range0.19–0.90.51–1.7
LDH (U/L)N50420.782
Median (IQR)226.5 (91)237 (118)
Range103–389142–507
Magnesium (mg/dL)N4621<0.001
Median (IQR)1.74 (0.16)2.15 (0.45)
Range1.41–3.431.7–2.71
Sodium (mmol/L)N5249<0.001
Median (IQR)138 (4)141 (3)
Range134–144120–147
Procalcitonin (ng/mL)N5147<0.001
Median (IQR)0.14 (0.19)0.06 (0.09)
Range0.03–95.50.02–15
PT—Prothrombin time (s)N5142<0.001
Median (IQR)1 (0.08)1.17 (0.16)
Range0.891.290.97–1.75
Urea (mg/dL)N5247<0.001
Median (IQR)11 (5)22 (11)
Range4–2012–75
Vitamin D3 25(OH) (ng/mL)N45240.776
Mean ± SD27.15 ± 10.8228.08 ± 16.31
Range6.8–56.30–62.5
Anti-SARS-CoV-2 IgG (ELISA) (index)N4920.596
Median (IQR)3.8 (4.1)7.35 (7.7)
Range1.8–78.13.5–11.2
Anti-SARS-CoV-2 IgA + IgM (ELISA) (index)N4920.056
Median (IQR)0.8 (2.8)21.85 (36.3)
Range0.1–403.7–40
IL-6 (pg/mL)N5229<0.001
Median (IQR)26.5 (31.6)5.06 (7.79)
Range1.5–1130–70
Troponin I (ng/mL)N52310.071
Median (IQR)2.75 (2.15)1.80 (2.7)
Range0–250–3.4
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Januszewski, M.; Ziuzia-Januszewska, L.; Jakimiuk, A.A.; Wierzba, W.; Gluszko, A.; Zytynska-Daniluk, J.; Jakimiuk, A.J. Is the Course of COVID-19 Different during Pregnancy? A Retrospective Comparative Study. Int. J. Environ. Res. Public Health 2021, 18, 12011. https://doi.org/10.3390/ijerph182212011

AMA Style

Januszewski M, Ziuzia-Januszewska L, Jakimiuk AA, Wierzba W, Gluszko A, Zytynska-Daniluk J, Jakimiuk AJ. Is the Course of COVID-19 Different during Pregnancy? A Retrospective Comparative Study. International Journal of Environmental Research and Public Health. 2021; 18(22):12011. https://doi.org/10.3390/ijerph182212011

Chicago/Turabian Style

Januszewski, Marcin, Laura Ziuzia-Januszewska, Alicja A. Jakimiuk, Waldemar Wierzba, Anna Gluszko, Joanna Zytynska-Daniluk, and Artur J. Jakimiuk. 2021. "Is the Course of COVID-19 Different during Pregnancy? A Retrospective Comparative Study" International Journal of Environmental Research and Public Health 18, no. 22: 12011. https://doi.org/10.3390/ijerph182212011

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop