Maternal and perinatal characteristics and outcomes of pregnancies complicated with COVID-19 in Kuwait

Background The effect of SARS-CoV-2 infection in pregnant women and newborns is incompletely understood. Preliminary data shows a rather fluctuating course of the disease from asymptomatic or mild symptoms to maternal death. However, it is not clear whether the disease increases the risk of pregnancy-related complications. The aim of the study is to describe the maternal and neonatal clinical characteristics and outcome of pregnancies with SARS-CoV-2 infection. Methods In this retrospective national-based study, we analyzed the medical records of all pregnant women infected with SARS-CoV-2 and their neonates who were admitted to New-Jahra Hospital (NJH), Kuwait, between March 15th 2020 and May 31st 2020. During the study period and as part of the public health measures, a total of 185 pregnant women infected with SARS-CoV-2, regardless of symptoms, were hospitalized at NJH, and were included. Maternal and neonatal clinical manifestations, laboratory tests and treatments were collected. The outcomes of pregnancies included miscarriage, intrauterine fetal death (IUFD), preterm birth and live birth were assessed until the end date of the outcomes follow-up (November 10th 2020). Results A total of 185 pregnant women infected with SARS-CoV-2 were enrolled with a median age of 31 years (interquartile range, IQR: 27.5–34), and median gestational age at diagnosis of SARS-CoV2 infection was 29 weeks (IQR: 18–34). The majority (88%) of these women had mild symptoms, with fever (58%) being the most common presenting symptom followed by cough (50.6%). At the time of the analysis, out of the 185, 3 (1.6%) of the pregnant women had a miscarriage, 1 (0.54%) had IUFD which was not related to COVID-19, 16 (8.6%) had ongoing pregnancies and 165 (89%) had a live birth. Only 2 (1.1%) of these women developed severe pneumonia and required intensive care. A total of 167 neonates with two sets of twins were born with median gestational age at birth was 38 (IQR: 36–39) weeks. Most of the neonates were asymptomatic, and only 2 of them tested positive on day 5 by nasopharyngeal swab testing. Conclusions In this national-based study, most of the pregnant women infected with SARS-CoV-2 showed mild symptoms. Although mother-to-child vertical transmission of SARS-CoV-2 is possible, COVID-19 infection during pregnancy may not lead to unfavorable maternal and neonatal outcomes. Supplementary Information Supplementary information accompanies this paper at 10.1186/s12884-020-03461-2.


Stratification Risk Factors by Age, Gender and Comorbidities
• Age ≥ 60 years and older • Male gender • Those with comorbidities (10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6% for hypertension, and 5.6% for cancer) Plus smokers. • Immunocompromised hosts (T-cell depleted medications; Corticosteroid equivalent to prednisone >15 mg per day for more than 2 months).

Stratification by Clinical Symptoms:
• Fever • Cough (usually dry) • Approximately 90% of patients present with more than one symptom, and 15% of patients present with fever, cough, and dyspnea • Patients may present with nausea or diarrhea 1 to 2 days prior to onset of fever and breathing difficulties.  15 . Imperative to start treatment early. In one study late initiation of Lopinavir/ritonavir did not improve mortality rate 16 . 6. Obtain CRP baseline and serially follow. 7. Ask virology lab to check cycle threshold (ct) value at the initiation of treatment and at 72 hours. 8. Obtain ECG daily. 9. Review above antibiotic regimen in 72 hours * Rationale for use: Hydroxychloroquine is an inexpensive and generally safe drug for short term use, with few drugdrug interactions. While it is unknown if it is effective to treat COVID-19, there is a favorable risk: benefit and cost ratio. Multiple trials are ongoing, and this recommendation will be updated when further data is available. The recent French study 13 showing combination of Hydroxychloroquine and Azithromycin achieved viral suppression is methodologically weak and has not been subjected to peer review. When limiting the analysis to those with comparable baseline cycle threshold values, combination therapy with hydroxychloroquine and azithromycin led to a similar proportion of negative testing by day 6 compared to hydroxychloroquine monotherapy. Furthermore, the study does not report the clinical outcomes of these patients, and it is unknown if reductions in viral load correlate with improvements in clinical outcomes. Thus, based on this limited (only 6 patients in combination group) and weak evidence, we recommend against the routine use of azithromycin for the treatment of COVID-19 at this time.
In patients <50 yo with comorbidities OR > 50 yo regardless of associated comorbidities, and mild pneumonia: 1. If no hospitalization in the past 90 days, start Ceftriaxone or Amoxicillin-Clavulanic Acid to treat secondary bacterial infection. In PCN-allergic patients, start Moxifloxacin. Treat for 5-7 days only. If hospitalized in the past 90 days -consider piperacillin-tazobactam 4.5 mg IV q8. If PCN allergic, consider Levofloxacin 500 mg IV/PO daily. Treat for 5-7 days only. 2. If the nasal MRSA screen is positive, consider MRSA coverage for 5 days only-Preferred agent is Teicoplanin (6 mg/kg IV q12 x 3 loading dose; then 6 mg/kg IV q daily) 10  • Alternative therapy if hydroxychloroquine is unavailable or if the patient has contraindications or adverse effects. • Adverse events: Hepatotoxicity, pancreatitis, diabetes, QT prolongation, lipid elevations, and fat redistribution • Major substrate and inhibitor of Cytochrome P450, and can cause severe drug-drug interactions.
Thorough evaluation of a patient's medication profile and clinical pharmacy consultation should be initiated before starting therapy. • Pregnancy: Lopinavir-ritonavir is safe to use during pregnancy.

Not Recommended (alphabetical order): Risk/benefit ratio does not favor use Angiotensin/RAS Blocking Agents (ACEi/ARBs) 17
Do not discontinue these therapies for COVID-19 disease. Multiple professional societies in cardiology and have reviewed the current data and conclude that the evidence suggesting discontinuation of ACEi/ARB therapy to decrease risk for more severe COVID-19 is not well supported at this time.

Azithromycin 12
No activity for SARS-CoV-2. Single study of combination therapy with hydroxychloroquine does not convincingly suggest added benefit to azithromycin combination therapy, given multiple study limitations and concern for antibiotic overuse.

Ibuprofen/NSAIDs 18
Do not discontinue these therapies for COVID-19 disease. Paracetamol is the preferred fever reducer for use in COVID-19. Although there has been theoretical concern raised for these agents worsening outcomes, no data currently exist to support this. FDA is not aware of scientific evidence connecting the use of NSAIDs, like ibuprofen, with worsening COVID-19 symptoms. The agency is investigating this issue further and will communicate publicly when more information is available.

Corticosteroids 19
There is significant interest and controversy surrounding the role of corticosteroids for the management of severe pneumonia due to coronaviruses. The potential benefit of these agents to blunt the