Coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) can cause severe adverse pregnancy outcomes, such as miscarriage, premature delivery, intrauterine growth restriction, and maternal death.
Vertical transmission of the virus responsible for 2019 novel coronavirus disease (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has not yet been detected, whereas perinatal transmission has been suspected in more than one case.
SARS and its effects on pregnant women
Severe acute respiratory syndrome (SARS) is caused by the SARS-coronavirus (SARS-CoV).
Manifestations of SARS consist of fever, chills, headache, malaise, and myalgia.
Diarrhea was seen in some patients.
The incubation period was estimated at a mean of 4.6 days, with a range of 2-14 days.
Transmission appeared to occur most often during the second week of illness when viral excretion is highest; there is no evidence that a person with SARS is contagious before symptom onset.
Pneumonia was nearly always seen in patients diagnosed with SARS, with mechanical ventilation being required in 10-20% of cases. Case fatality rate was estimated at 9-10% (Table).
Table – Comparison of Characteristics of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19)
| Characteristics | Severe Acute Respiratory Syndrome | Middle East Respiratory Syndrome | Coronavirus Disease-2019 |
| First patients reported | Guangdong, China, November 2002 | Zarga, Jordan, April 2012 and Jeddah, Saudi Arabia, June 2012 | Wuhan, China, December 2019 |
| Virus | SARS-CoV | MERS-CoV | SARS-CoV-2 |
| Type of coronavirus | betacoronavirus | betacoronavirus | betacoronavirus |
| Host cell receptor | Angiotensin converting enzyme 2 | Dipeptidyl peptidase 4 | structural analysis suggests Angiotensin converting enzyme 2 receptor52 |
| Sequence similarity | reference | 79% to SARS-CoV, 50% to MERS-CoV35 | |
| Animal hosts | Bats (natural reservoir), masked palm civet and raccoon dogs may be intermediate hosts | Bats (natural reservoir), dromedary camel (intermediate host) | Bats, animal sold at the seafood market in Wuhan might represent an intermediate host35 |
| Incubation period | |||
| Mean (95% CI: days) | 4.6 (3.8-5.8) | 5.2 (1.9-14.7) | 5.2 days (95% confidence interval [CI], 4.1 to 7.0); 95th percentile of the distribution was 12.5 days33 |
| Range (days) | 2-14 | 2-13 | 2-14 |
| Time from illness onset until hospitalization | 2-8 days | 0-16 days | 12.5 days (mean) (95% CI, 10.3 to 14.8) – onset before January 1 9.1 days (mean); 95% CI, 8.6 to 9.7 (onset January 1-11)33 |
| Basic reproduction number (R0) ** | 2-3 | <1 | 2.2 (95% CI, 1.4 to 3.9)33 |
| Patient characteristics | |||
| Adults | 93% | 98% | Nearly all reported patients are adults |
| Children | 5-7% | 2% | Children have been infrequently reported (<1% of cases)39 |
| Age range (years) | 1-91 | 1-94 | 10-89 years |
| Average age (years) | Mean 39.9 | Median 50 | 59 years (median)33 |
| Sex ratio (M:F) | 43%:57% | 64.5%:35.5% | 56%:44%33 |
| Mortality | |||
| Case fatality rate overall | 9.6% | 35-40% | Initial estimate is 1%38 |
| Clinical Manifestations | From hospitalized patients32,36,37 | ||
| Fever | 99-100% | 98% | 83-100% |
| Cough | 62-100% | 83% | 59-82% |
| Myalgia | 45-61% | 32% | 11-35% |
| Headache | 20-56% | 11% | 7-8% |
| Diarrhea | 20-25% | 26% | 2-10% |
| Laboratory findings | |||
| Radiographic abnormalities on chest imaging | 94-100% | 90-100% | 100% |
| Leukopenia | 25-35% | 14% | 9-25% |
| Lymphopenia | 65-85% | 32% | 35-70% |
| Thrombocytopenia | 40-45% | 36% | 5-12% |
*Modified from Rasmussen et al.[23]
**Basic reproduction number – defined as average number of people who will become infected from a single infected person
Abbreviations: SARS-CoV, severe acute respiratory syndrome coronavirus; MERS-CoV, Middle East respiratory syndrome coronaviru; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2
Fecal-oral transmission and transmission via fomites have also been reported.[8]
Airborne spread due to inhalation of small particle aerosols may also be possible.
Although there were relatively few documented cases of SARS occurring during pregnancy, several case reports and small clinical studies have described the clinical effects in pregnant women and their infants.
In reviewing these reports describing pregnant women with SARS in China it is possible, and perhaps even probable, that some of the same patients were included in more than one publication.
However, even if this is the case, there is no doubt that SARS coronavirus infection was found to be associated with severe maternal illness, maternal death, and spontaneous abortion [19,28,29,30,31].
Martha Anker, an expert in statistics formerly with the WHO and the University of Massachusetts, estimated that more than 100 cases of SARS-CoV infection occurred in pregnant women, which warrants closer inspection [27].
The clinical outcomes among pregnant women with SARS in Hong Kong were worse than those occurring in infected women who were not pregnant [32].
Wong et al. [29] evaluated the obstetrical outcomes from a cohort of pregnant women who developed SARS in Hong Kong during the period of 1 February to 31 July 2003 – in which 12 pregnant women were identified.10 The case-fatality rate was 25% (3 deaths).
Clinical and laboratory findings were similar to those seen in the non-pregnant population.
Pneumonia on chest radiograph or CT was seen in all patients.
Major medical complications included adult respiratory distress syndrome in four, disseminated intravascular coagulopathy (DIC) in three, renal failure in three, secondary bacterial pneumonia in two, and sepsis in two patients.
Four of the 7 women (57%) that presented during the 1st trimester sustained spontaneous miscarriages, likely a result of the hypoxia that was caused by SARS-related acute respiratory distress.
Among the 5 women who presented after 24 weeks gestation, 4 had preterm deliveries (80%).
A case-control study to determine the effects of SARS on pregnancy compared 10 pregnant and 40 non-pregnant women with the infection at the Princess Margaret Hospital in Hong Kong [27,33].
There were 3 deaths among the pregnant women with SARS (maternal mortality rate of 30%) and no deaths in the non-pregnant group of infected women (P = 0.006). Renal failure (P = 0.006) and disseminated intravascular coagulopathy (P = 0.006) developed more frequently in pregnant SARS patients when compared with the non-pregnant SARS group.
Six pregnant women with SARS required admission to the intensive care unit (ICU) (60%) and 4 required endotracheal intubation (40%), compared with a 12.5% intubation rate (P = 0.065) and 17.5% ICU admission rate (P = 0.012) in the non-pregnant group.
Maxwell et al. [32] reported 7 pregnant women infected with SARS-CoV who were followed at a designated SARS unit—2 of the 7 died (CFR of 28%), and 4 (57%) required ICU hospitalization and mechanical ventilation.
In contrast, the mortality rate was less than 10% and mechanical ventilation rate less than 20% among non-pregnant, age-matched counterparts who were not infected with SARS-CoV.
Two women with SARS recovered and maintained their pregnancy but had infants with IUGR. Among the live newborn infants, none had clinical or laboratory evidence for SARS-CoV infection.
Zhang et al. [34] described SARS-CoV infections in 5 primagravidas from Guangzhou, China at the height of the SARS epidemic.
Two of the mothers became infected in the 2nd trimester, and 3 developed infection in the 3rd trimester.
All 5 pregnant women had fever and abnormal chest radiographs; 4 had cough; 4 developed hypoalbuminemia; 3 had elevated alanine aminotransferase levels (ALT), 3 had chills or rigor, 2 had decreased lymphocytes, and 2 had decreased platelets.
One pregnant woman required intensive care, but all recovered and there were no maternal deaths.
The 5 infants were clinically evaluated, and none had evidence of SARS.
Two pregnant women with SARS were reported from the United States. In a detailed case report, Robertson et al. [35] described a 36-year-old pregnant woman with an intermittent cough of approximately 10 days duration and no fever.
While travelling in Hong Kong during the 2003 epidemic, she was exposed at her hotel to a person subsequently known to be infected with SARS-CoV.
At 19 weeks gestation she developed fever, anorexia, headache, increasing cough, weakness, and shortness of breath.
Upon returning to the United States she was hospitalized with pneumonia.
Obstetrical ultrasounds revealed a low-lying placenta (placenta previa) but were otherwise normal.
Following her discharge home and clinical recovery, she was found to have antibodies to SARS-CoV. She underwent cesarean section at 38 weeks gestation because of the placenta previa and a healthy baby girl was delivered [35,36].
The placenta was interpreted as being normal.
At 130 days post-maternal illness, maternal serum and whole blood, swabs from maternal nasopharynx and rectum, post-delivery placenta, umbilical cord blood, amniotic fluid, and breast milk were collected for analysis-no viral RNA was detected in specimens tested by reverse transcriptase polymerase chain reaction (RT-PCR).
Antibodies to SARS-CoV were detected from maternal serum, umbilical cord blood, and breast milk by enzyme immunoassay (EIA) and indirect immunofluorescence assay. No clinical specimens (except for cord blood) were available for testing from the infant.
The second case in the USA occurred in a 38-year-old woman who had travelled to Hong Kong at 7 weeks gestation where she was exposed to SARS-CoV in the same hotel as the aforementioned American woman [37].
Following her return to the United States, her husband developed the clinical onset of SARS, and 6 days later she became ill with fever, myalgia, chills, headache, coryza, and a productive cough with shortness of breath and wheezing.
Following her hospitalization for SARS she recovered, serum samples taken on days 28 and 64 post-onset of illness were positive for antibodies to SARS-CoV by enzyme immunoassay and immunofluorescent assays. Her pregnancy continued and was unremarkable except for developing elevated glucose levels.
A cesarean section that was performed at 36 weeks gestation due to preterm rupture of membranes and fetal distress resulted in a healthy baby boy.
At the time of delivery, the mother’s serum samples were positive for antibodies to SARS-CoV, but samples taken of umbilical cord blood and placenta were negative. Breast milk sampled 12 and 30 days after delivery were also negative for SARS-CoV antibodies.
Specimens evaluated from maternal blood, stool, and nasopharynx samples, as well as umbilical cord blood of the infant, were all negative for coronavirus RNA by RT-PCR.
Neonatal stool samples obtained on days-of-life 12 and 30 were also negative for viral RNA.
From Canada, Yudin et al. [38] reported a 33-year-old pregnant woman who was admitted to the hospital at 31 weeks gestation with a fever, dry cough, and abnormal chest radiograph demonstrating patchy infiltrates. She had acquired SARS from contact with an infected family member.
Following a 21-day stay in the hospital, during which she did not require ventilatory support, her convalescent antibody titers were positive for coronavirus infection. She had a normal labor and delivery and her newborn girl had no evidence of infection.
In a study of 5 liveborn neonates who were delivered to women infected with SARS-CoV during the Hong Kong epidemic, results from multiple tests – including serial RT-PCR assays, viral culture, and paired neonatal serological titers – were negative for SARS-CoV [39].
None of the 5 neonates developed any clinical signs or symptoms of respiratory infection or compromise.
Fortunately, there were no cases of vertical transmission identified among pregnant women infected with SARS-CoV during the 2002–2003 Asian epidemic [27,30,31,39,40], and with the exception of a small cluster of cases that recurred in late 2003, no new cases of SARS have occurred.
Placental Pathology of SARS
In the only reported study of the placental pathology of mothers with SARS, Ng et al. [41] reported the findings from 7 pregnant women infected with SARS-CoV.
In the case of 2 women who were convalescing from SARS-CoV infection during the 1st trimester of pregnancy, the placentas were found to be normal.
Three placentas were delivered from pregnancies in which the mothers had acute SARS-CoV infection – these were abnormal and demonstrated increased subchorionic and intervillous fibrin, a finding that can be associated with abnormal maternal blood flow to the placenta.
In the placentas of 2 women who were convalescing from SARS-CoV infection in the 3rd trimester of pregnancy the placentas were highly abnormal.
They showed extensive fetal thrombotic vasculopathy with areas of avascular chorionic villi – chronic findings of fetal vascular malperfusion.
These 2 pregnancies also were complicated by oligohydramnios and had poor obstetrical outcomes – both infants had developed IUGR.
It is interesting that villitis, the microscopic finding of inflammation of the chorionic villi that is the histologic hallmark of many maternal hematogenous infections that are transmitted through the placenta to the fetus, was not identified in any of these placentas.
Safe Management of Pregnant Women with SARS
Similar to other coronavirus infections, SARS-CoV is easily spread from person-to-person via respiratory droplets and secretions as well as through nosocomial contacts [42,43].
In addition to transmission of SARS-CoV through natural aerosols from infected patients, it was found that in Hong Kong the SARS-CoV could also be transmitted by mechanical aerosols [44].
Environmental factors had an important role when it was discovered that during the Amoy Gardens housing estate outbreak as many as two-thirds of infected persons had diarrhea, SARS-CoV was excreted in their stools, and that aerosols arising from the flushing of toilets could transmit the virus [44].
Healthcare facilities were also an important source of new SARS infections during the 2002–2003 epidemic, and healthcare workers were also at high risk for acquiring the infection.
In order to address the safety issues for the obstetrical management and delivery of pregnant women with SARS, guidelines were prepared by the Canadian Task Force on Preventive Health Care and the Society of Obstetricians and Gynaecologists of Canada [45].
These recommendations include:
- “All hospitals should have infection control systems in place to ensure that alerts regarding changes in exposure risk factors for SARS or other potentially serious communicable diseases are conveyed promptly to clinical units, including the labour and delivery unit.
- At times of SARS outbreaks, all pregnant patients being assessed or admitted to the hospital should be screened for symptoms of and risk factors for SARS.
- Upon arrival in the labour triage unit, pregnant patients with suspected and probable SARS should be placed in a negative pressure isolation room with at least 6 air exchanges per hour. All labour and delivery units caring for suspected and probable SARS should have available at least one room in which patients can safely labour and deliver while in need of airborne isolation.
- If possible, labour and delivery (including operative delivery or Caesarean section) should be managed in a designated negative pressure isolation room, by designated personnel with specialized infection control preparation and protective gear.
- Either regional or general anaesthesia may be appropriate for delivery of patients with SARS.
- Neonates of mothers with SARS should be isolated in a designated unit until the infant has been well for 10 days, or until the mother’s period of isolation is complete. The mother should not breastfeed during this period.
- A multidisciplinary team, consisting of obstetricians, nurses, pediatricians, infection control specialists, respiratory therapists, and anaesthesiologists, should be identified in each unit and be responsible for the unit organization and implementation of SARS management protocols.
- Staff caring for pregnant SARS patients should not care for other pregnant patients. Staff caring for pregnant SARS patients should be actively monitored for fever and other symptoms of SARS. Such individuals should not work in the presence of any SARS symptoms within 10 days of exposure to a SARS patient.
- All health care personnel, trainees, and support staff should be trained in infection control management and containment to prevent spread of the SARS virus.
- Regional health authorities in conjunction with hospital staff should consider designating specific facilities or health care units, including primary, secondary, or tertiary health care centers, to care for patients with SARS or similar illnesses.”
Coronavirus Disease 2019 (COVID-19)
Clinical, epidemiologic, and viral characteristics
Respiratory illness caused by a novel coronavirus (now referred to as SARS-CoV-2) was first noted in December of 2019 in Wuhan, Hubei Province, China. The WHO China Country office was notified of an outbreak of pneumonia of unknown etiology on December 31, 2019 (Figure 2).
Between December 31, 2019 and January 3, 2020, 44 cases were reported to the WHO.
On January 7, 2020, Chinese authorities identified a novel coronavirus as the cause.
The virus has quickly spread first through Wuhan and subsequently to other areas of China and other countries in the world (Figure 1). Early data suggested an association between the Huanan Seafood Wholesale Market and COVID-19 with 27 of 41 cases in one report [52] and 26 of 47 in another report [73]with epidemiologic links to the market, leading to closure of the market on January 1, 2020. Given that the earliest case reported (illness onset on December 1, 2019) [72] did not have exposure to the market raises the possibility that the initial emergence into humans occurred elsewhere.
However, sampling of the market’s environment supports the market’s importance in early transmission of the virus. Later cases were much less likely to have visited the market, supporting the role of person-to-person transmission in later cases.
The SARS-CoV-2 is a betacoronavirus similar to SARS-CoV and MERS-CoV (Table).
Sequencing data show that the SARS-CoV-2 is most closely related to coronaviruses found in bats, with more than 85% nucleotide identity with a bat SARS-like CoV. [54,55]
The virus has 79% nucleotide identity to SARS-CoV and about 50% to MERS-CoV.35 Bats appear to be the natural reservoirs of both SARS-CoV and MERS-CoV. The emergence of these viruses in humans has been attributed to host switching: the virus “jumped” from an intermediary host species (e.g., civet cats for SARS-CoV and dromedary camels for MERS-CoV) to humans. An intermediary host species is thought to be likely for SARS-CoV-2,35 although it has been yet to be identified.
Sequence data that show a high degree (>99.98%) of similarity of the virus among different patients, suggesting a recent emergence in humans.
Clinical manifestations of COVID-19 are similar to those with SARS and MERS (Table).
Studies of hospitalized patients with COVID-19 show that patients commonly develop severe pneumonia with 23-32% admitted to the intensive care unit and 17-29% of cases progressing to acute respiratory distress syndrome (ARDS). [ 52,56,57]
Among hospitalized patients, 4-15% have died. [ 52,56,57]
Overall case fatality ratio estimates (including asymptomatic and symptomatic infections) appear to be in the range of 1% (95% confidence interval 0.5-4%),[58] although these estimates should be considered preliminary.
Average age of hospitalized patients was 49-56 years, with 32-51% having an underlying illness.
Most (54-73%) patients were men.
Children with COVID-19 appear to be rarely identified, with only 28 children reported as of January 30, 2020 (<1% of total), and most of those identified had mild symptoms.[59]
No pregnant women were reported in any of these initial cohorts.
Common manifestations among hospitalized patients were fever (83-100%), cough (59-82%), myalgia (11-35%), headache (7-8%), and diarrhea (2-10%).
All patients had abnormalities on radiographic imaging of the chest.
Person-to-person transmission of SARS-CoV-2 is thought to be similar to transmission of influenza and other respiratory pathogens; respiratory droplets are formed when an infected person coughs or sneezes and these droplets are inhaled by close contacts, generally within 6 feet.
It is unclear if infection can be transmitted from fomites.
Fecal-oral transmission might be possible, given that SARS-CoV-2 has been identified in stool specimens [60] and SARS-CoV might have been transmitted in this manner.[61] The basic reproduction number, R0 (the average number of people who will become infected from a single infected person in a population where all persons are susceptible) is affected by factors such as the duration of infectivity, the transmissibility of the pathogen, and the number of susceptible contacts.
Measles, which is highly infective, has a R0 of 12-18, while 2009 H1N1 influenza and SARS have an R0 of 1.2-1.6 and 2-5, respectively.[62] Current estimates of R0 for SARS-CoV-2 places it at 2.2 (95% CI, 1.4 to 3.9) [53].
As with SARS and MERS, nosocomial transmission is playing a key role in transmission, presumed to be responsible for infection of 29% of affected health professionals and 12% of hospitalized patients in a recent study.[57]
Implications of COVID-19 for pregnant women
In the midst of a rapidly evolving outbreak that could have significant effects on our public health and medical infrastructure, the unique needs of pregnant women should be included in preparedness and response plans.
In previous outbreaks, clinicians have at times been reluctant to treat or vaccinate pregnant women because of concerns for fetal safety[63].
It is critical that pregnant women not be denied potentially life-saving interventions in the context of a serious infectious disease threat unless there is a compelling reason to exclude them.
As with all decisions regarding treatment during pregnancy, carefully weighing of the benefits of interventions for the mother and fetus with potential risks is necessary.
As surveillance systems for cases of COVID-19 are established, it is essential that information on pregnancy status, as well as maternal and fetal outcomes, be collected and reported.
Susceptibility to and severity of COVID-19 in pregnancy
Although data are limited, there is no evidence from other severe coronavirus infections (SARS or MERS) that pregnant women are more susceptible to infection with coronavirus.
Thus far, in this outbreak of novel coronavirus infection, more men have been affected than Women [52.53.56.57].
This observed gender difference could be due to differences in reporting, susceptibility, exposure, or recognition and diagnosis of infection.
There are no data to inform whether pregnancy increases susceptibility to COVID-19.
Previous data on SARS and MERS suggest that clinical findings during pregnancy can range from no symptoms to severe disease and death.
The most common symptoms of COVID-19 are fever and cough, with more than 80% of hospitalized patients presenting with these symptoms [56].
In a recent study by Chen et al. [64] , nine women diagnosed with COVID-19 during the third trimester of pregnancy were reported.
In this small series, clinical presentation was similar to that seen in nonpregnant adults, with fever in seven, cough in four, myalgia in three, and sore throat and malaise each in two women.
Five had lymphopenia. All had pneumonia, but none required mechanical ventilation, and none died.
All women had a cesarean delivery, and Apgars were 8-9 at 1 minute and 9-10 at 5 minutes.
In a second series of nine pregnancies with ten infants (one set of twins) reported by Zhu et al. [65], symptom onset was before delivery (1-6 days) in four, on the day of delivery in two, and after delivery (1-3 days) in three cases.
Clinical presentation of COVID-19 was similar to that seen in nonpregnant patients.
Among the nine pregnancies, intrauterine fetal distress was noted in six, seven were cesarean deliveries, and six infants were born preterm.
Based on these limited reports, and the available data from other respiratory pathogens such as SARS and influenza, it is unknown whether pregnant women with COVID-19 will experience more severe disease.
Travel guidance for pregnant women
Travel recommendations have been instituted to limit exposure to persons in the United States. All persons, including pregnant women, should not travel to China. On February 2, 2020, the U.S. State Department upgraded their travel advisory to level 4, the highest level of travel advisory.
Obstetric providers should obtain a detailed travel history for all patients and should specifically ask about travel in the past 14 days to areas experiencing widespread transmission of SARS-CoV-2. Currently this is limited to China, but this situation is rapidly evolving and obstetricians should stay alert to the global situation by consulting the CDC website and following media coverage.
Vaccination in pregnancy
There is currently no vaccine to prevent COVID-19. Since posting of a SARS-CoV-2 virus genetic sequence online on January 10, 2020, multiple organizations, including the National Institutes of Health, have been working to rapidly develop a COVID-19 vaccine.
Development of this vaccine builds on and benefits from work on SARS and MERS vaccines [66].
However, it is not known how quickly a safe and effective vaccine may be readily available.
Infection control measures and diagnostic testing
All patients, including pregnant women, should be evaluated for fever and signs and symptoms of a respiratory infection. Ideally, screening procedures begin before arrival on a labor and delivery unit or prenatal care clinic.
For example, when scheduling appointments, patients should be instructed what to do if they have respiratory symptoms on the day of their appointment or if a patient calls triage prior to presentation, respiratory signs and symptoms should be assessed over the telephone. Those patients with respiratory symptoms should be separated from other waiting patients and a facemask should be placed on them.
Patients who meet criteria for a Person Under Investigation (Box 1) should be immediately placed in an Airborne Infection Isolation Rooms (single-patient rooms at negative pressure).
Once in isolation, the patient’s facemask may be removed. Health care personnel should adhere to standard, contact and airborne precautions. Infection control personnel and local/state health departments should be notified immediately; local/state health departments can help to arrange testing of relevant specimens (upper and lower respiratory specimens and serum are currently recommended; other specimens may also be sent).
BOX 1 – Criteria to Guide Evaluation of Persons Under Investigation for Coronavirus Disease 2019 (COVID-19)
| Clinical Features | AND | Epidemiologic Risk |
| Fever* or signs/symptoms of lower respiratory illness (e.g., cough or shortness of breath | AND | Any person, including health care workers, who has had close contact** with a laboratory-confirmed COVID-19 patient within 14 days of symptom onset |
| Fever* and signs/symptoms of a lower respiratory illness (e.g., cough or shortness of breath | AND | A history of travel from Hubei Province China within 14 days of symptom onset |
| Fever* and signs/symptoms of a lower respiratory illness (e.g., cough or shortness of breath) requiring hospitalization | AND | A history of travel from mainland China within 14 days of symptom onset |
*Fever may be subjective or confirmed
**Close contact is defined as:
- being within ~6 feet (2 meters) of a COVID-19 case for a prolonged period of time while not wearing recommended personal protective equipment (e.g., gowns, gloves, NIOSH-certified disposable N95 respirator, eye protection); close contact can occur while caring for, living with, visiting, or sharing a health care waiting area or room with a COVID-19 case
OR
- having direct contact with infectious secretions of a COVID-19 case (e.g., being coughed on) while not wearing recommended personal protective equipment.
The criteria are intended to serve as guidance for evaluation. Patients should be evaluated and discussed with public health departments on a case-by-case basis if their clinical presentation or exposure history is equivocal (e.g., uncertain travel or exposure).
From: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html#foot1
Management of COVID-19 in pregnancy
General principles regarding management of COVID-10 during pregnancy include early isolation, aggressive infection control procedures, testing for SARS-CoV-2 and co-infection, oxygen therapy as needed, avoidance of fluid overload, empiric antibiotics (due to secondary bacterial infection risk), fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multi-specialty consultations (Box 2).
BOX 2 – Principles for Management of Pregnant Women with Confirmed or Suspected Coronavirus Disease 2019 (COVID-19) [68,73,74) 48,53,54
- Patients with respiratory
symptoms should adhere to respiratory hygiene, cough etiquette, and hand
hygiene. Ensure rapid triage of pregnant patients with respiratory symptoms.
Patients with respiratory symptoms should wear a facemask and wait in a
separate, well ventilated waiting area at least 6 feet from other people.
- Confirmed and suspected cases of COVID-19 should be isolated as soon as possible in an Airborne Infection Isolation Room (AIIR). If an AIIR is not available, consider transfer to a hospital with an AIIR.
- Implement CDC infection prevention and control procedures for healthcare providers including standard, contact, and airborne precautions. Eye protection and properly-fitted N95 respirators should be used. Provide additional staff training in correct use of personal protective equipment (PPE) including correct donning, doffing and disposal of PPE.
- Contact hospital infection personnel.
- In coordination with local/state health department, collect and send relevant specimens for diagnostic SARS-CoV-2 testing.
- Limit visitor and health care personnel access to patient rooms with a confirmed or suspected case.
- Pregnancy should be considered a potentially increased risk condition and monitored closely including fetal heart rate and contraction monitoring.
- Consider early oxygen therapy (target O2 saturations ≥95% and/or pO2 ≥70mmHg). Consider early mechanical ventilation with evidence of advancing respiratory failure. Non-invasive ventilation techniques may have a small increased risk of aspiration in pregnancy.
- Use intravenous fluids conservatively unless cardiovascular instability is present.
- Screen for other viral respiratory infections and bacterial infections (due to risk of co- infections).
- Consider empiric antimicrobial therapy (because of risk for superimposed bacterial infections).
- Consider empiric treatment for influenza, pending diagnostic testing.
- Do not routinely use corticosteroids. Use of steroids to promote fetal maturity with anticipated preterm delivery can be considered on individual basis.
- If septic shock is suspected, institute prompt, targeted management.
- Delivery and pregnancy termination decisions should be based on gestational age, maternal condition, and fetal stability, and maternal wishes.
- Consult with specialists in obstetrics, maternal-fetal medicine, neonatology, intensive care, anesthesia, and nursing.
- Communicate with patients and families regarding diagnosis, clinical status and management wishes.
*All guidance should be considered subject to revision as additional data on pregnant women with COVID-19 become available.
Team-based management is recommended for pregnancies managed in a health care facility and should include a determination of the optimal clinical unit on which to provide care.
Ability to provide surveillance for early detection of a worsening maternal course of illness, as well as an ability to monitor for evidence of obstetric complications (e.g., preterm labor or fetal compromise), are needed.
Changes in fetal heart rate pattern may be an early indicator of maternal respiratory deterioration.
Based on experience with SARS and MERS, severe respiratory failure might occur in pregnant women, and in the most severe cases, mechanical ventilation might not be sufficient to support adequate oxygenation. If that occurs, limited literature suggests a potential role of extracorporeal membrane oxygenation (ECMO) in pregnancy; use should only be considered in centers that have experience with this technique.[67].
Whether delivery provides benefit to a critically ill mother is unknown; decisions regarding delivery should consider the gestational age of the fetus and should be made in conjunction with the neonatologist [48].
There are currently no antiviral medications approved by the US Food and Drug Administration for treatment of COVID-19, although broad-spectrum antivirals used in animal models of MERS are being evaluated for activity against SARS-CoV-2 [66].
Corticosteroids for the treatment of coronavirus-associated pneumonia should be avoided unless other indications are present because they were not shown to be beneficial in MERS and could lead to delayed MERS-CoV clearance [69].
Therefore, decisions about the use of corticosteroids for fetal lung maturity should be made in consultation with infectious disease specialists and maternal-fetal medicine consultants.
All guidance should be considered subject to revision as additional data on pregnant women with COVID-19 become available.
Care of infants born to mothers with COVID-19
Although the limited experience with newborn evaluations after delivery with SARS and MERS has not identified cases of maternal-to-fetal transmission, reports have appeared in the media of a 30-hour infant who was diagnosed with COVID-19, suggesting the possibility of in utero transmission.[70] However, insufficient information is included in media reports to rule out perinatal or postnatal modes of transmission.
Data from the recent case series published by Chen et al.[64] and Zhu et al. [65] of 18 women (19 infants) infected in the third trimester of pregnancy with SARS-CoV-2 identified no laboratory evidence of vertical transmission.
Testing of amniotic fluid, cord blood, and neonatal throat swab samples was negative for SARS-CoV-2 in the six patients reported by Chen et al. [64] In the report by Zhu et al., [65] some infants were symptomatic (shortness of breath in six, cyanosis in three, gastric bleeding in two, and one baby died of multiple organ failure and DIC); however, throat swab testing of all infants was negative for SARS-CoV-2 , suggesting that these neonatal complications might not be related intrauterine transmission.
Thus, at this time, it is unknown if SARS-CoV-2 can be transmitted from mother-to-fetus. Given the current lack of information, it seems reasonable to assume that a newborn born to a mother with COVID-19 at delivery could possibly be infected, either in utero or perinatally, and thus should be placed in isolation to avoid exposure to other newborns.
Although the ideal setting for a healthy infant is within a healthy mother’s room, temporary separation of an ill mother and her infant, as was recommended during pandemic H1N1, [71] seems prudent.
Whether COVID-19 can be transmitted through breastmilk is unknown.
We are aware of a single report of SARS-CoV testing of breastmilk in a mother who had recovered from SARS and no viral RNA was detected; however, the specimen was collected ~130 days after illness nset.[15]
SARS-CoV antibodies were seen in breastmilk of that patient, [15] but not in another patient who was infected at 7 weeks gestation with breastmilk tested at postpartum days 12 and 30. [16]
Breastmilk was tested for SARS-CoV-2 in six of the mothers reported by Chen et al. [64]; all specimens were negative. Until additional data are available, mothers who intend to breastfeed and are well enough to express breastmilk should be encouraged to do so; breastfeeding can be instituted after she is no longer considered infectious. No data are available to guide length of separation and will need to be decided on a case-by-case basis after discussion between infection control experts and neonatologists.
Current Status of 2019-nCoV (SARS-CoV-2) Infection of Pregnant Women and Neonates
On 5 February 2020 it was reported by multiple media outlets that a newborn infant delivered during the epidemic in Wuhan had tested positive for 2019-nCoV at the Wuhan Children’s Hospital in Hubei Province 30 hours following its birth.
According to the official Xinhua news agency, the infant was delivered on 2 February to a mother who had tested positive for the virus.
Reports have stated that the infant had stable vital signs, no fever or cough, but had shortness of breath together with abnormal chest radiographs and abnormalities of liver function [76,77,78]. Dr. Zeng Lingkong, Chief Physician at the Neonatal Medicine Department of the hospital, said [78],
“This reminds us to pay attention to mother-to-child being a possible route of coronavirus transmission”
The hospital also provided information about a previous case of a baby that had been delivered on 13 January 2020. Following its birth, the infant’s nanny was diagnosed with 2019-nCoV, and the mother was diagnosed days later [76].
On 29 January the baby began to develop symptoms. According to Dr. Zeng Lingkong [76],
“Whether it was the baby’s nanny who passed the virus to the mother who passed it to the baby, we cannot be sure at the moment.
But we can confirm that the baby was in close contact with patients infected with the new coronavirus, which says newborns can also be infected”
In considering whether these and future cases of neonatal infection are acquired prior to delivery, it is important to remember that newborn infants can acquire an infection in other ways beyond intrauterine maternal-fetal transmission.
In some cases, viral infection can be acquired when the infant passes through the birth canal during a vaginal delivery or through post-partum breast feeding, although these mechanisms would be highly unusual for a respiratory virus.
Neonatal infection from respiratory viruses can occur after delivery through such mechanisms as inhalation of the agent through aerosols produced by coughing from the mother, relatives or healthcare workers or other sources in the hospital environment.
Based upon past experience with pregnant women who developed MERS and SARS, and realizing that the numbers are limited, there has never been confirmed intrauterine coronavirus transmission from mother to fetus. Discussing the most recent baby to be diagnosed with the 2019-nCoV infection, Dr. Stephen Morse, an epidemiologist at the Mailman School of Public Health at Columbia University stated [77],
“It’s more likely that the baby contracted the virus from the hospital environment, the same way healthcare workers get infected by the patients they treat,”
“It’s quite possible that the baby picked it up very conventionally-by inhaling virus droplets that came from the mother coughing.”
And according to Dr. Paul Hunter, Professor of Medicine at the University of East Anglia [79],
“As far as I am aware there is currently no evidence that the novel coronavirus can be transmitted in the womb. When a baby is born vaginally it is exposed to the mother’s gut microbiome, therefore if a baby does get infected with coronavirus a few days after birth we currently cannot tell if the baby was infected in the womb or during birth.”
Reference
8. Hui DSC, Zumla A. Severe acute respiratory syndrome: Historical, epidemiologic, and clinical features. Infect Dis Clin North Am. 2019;33:869-889.
10. Wong SF, Chow KM, Leung TN, et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol. 2004;191:292-297
15. Robertson CA, Lowther SA, Birch T, et al. SARS and pregnancy: a case report. Emerg Infect Dis. 2004;10:345-348.
16. Stockman LJ, Lowther SA, Coy K, Saw J, Parashar UD. SARS during pregnancy, United States. Emerg Infect Dis. 2004;10:1689-1690.
19. Lau KK, Yu WC, Chu CM, Lau ST, Sheng B, Yuen KY. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis. 2004;10:342-344.
27. Assiri A, Abedi GR, Al Masri M, Bin Saeed A, Gerber SI, Watson JT. Middle East respiratory syndrome coronavirus infection during pregnancy: A report of 5 cases from Saudi Arabia. Clin Infect Dis. 2016;63:951-953.
28. Malik A, El Masry KM, Ravi M, Sayed F. Middle East respiratory syndrome coronavirus during pregnancy, Abu Dhabi, United Arab Emirates, 2013. Emerg Infect Dis. 2016;22:515-517.
29.Payne DC, Iblan I, Alqasrawi S, et al. Stillbirth during infection with Middle East respiratory syndrome coronavirus. J Infect Dis. 2014;209:1870-1872.
30. Racelis S, de los Reyes VC, Sucaldito MN, Deveraturda I, Roca JB, Tayag E. Contact tracing the first Middle East respiratory syndrome case in the Philippines, February 2015. Western Pac Surveill Response J. 2015;6:3-7.
31. Jeong SY, Sung SI, Sung JH, et al. MERS-CoV Infection in a pregnant woman in Korea.
J Korean Med Sci. 2017;32:1717-1720.
32. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020.
33. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020.
34. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020.
35. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020.
36. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020.
37. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients With 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020.
38. Dorigatti I, Okell L, Cori A, et al. Report 4: Severity of 2019-novel coronavirus (nCoV). WHO Collaborating Centre for Infectious Disease Modelling, MRC Centre for Global Infectious Disease Analysis, Imperial College London. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida- fellowships/Imperial-College-2019-nCoV-severity-10-02-2020.pdf Accessed February 11, 2020.
39. Shen KL, Yang YH. Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue. World J Pediatr. 2020.
40. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel noronavirus in the United States. N Engl J Med. 2020.
41. Ng, W.F.; Wong, S.F.; Lam, A.; Mak, Y.F.; Yao, H.; Lee, K.C.; Chow, K.M.; Yu, W.C.; Ho, L.C. The placentas of patients with severe acute respiratory syndrome: A pathophysiological evaluation. Pathology 2006, 38, 210–218.
42. Poutanen, S.M.; Low, D.E.; Henry, B.; Finkelstein, S.; Rose, D.; Green, K.; Tellier, R.; Draker, R.; Adachi, D.; Ayers, M.; et al. Identification of severe acute respiratory syndrome in Canada. N. Engl. J. Med. 2003, 348, 1995–2005.
43. Seto, W.H.; Tsang, D.; Yung, R.W.; Ching, T.Y.; Ng, T.K.; Ho, M.; Ho, L.M.; Peiris, J.S.M.; Advisors of Expert SARS group of Hospital Authority. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome. Lancet 2003, 361, 1519–1520.
44. Hung, L.S. The SARS epidemic in Hong Kong: What lessons have we learned? J. R. Soc. Med. 2003, 96, 374–378.
45. Maxwell, C.; McGeer, A.; Tai, K.F.Y.; Sermer, M.; Maternal Fetal Medicine Committee; Infectious Disease Committee. Management guidelines for obstetric patients and neonates born to mothers with suspected or probable severe acute respiratory syndrome (SARS). J. Obstet. Gynaecol. Can. 2009, 31, 358–364.
52. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020.
53. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020.
54. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020.
55. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020.
56. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020.
57. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients With 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020.
58. Dorigatti I, Okell L, Cori A, et al. Report 4: Severity of 2019-novel coronavirus (nCoV). WHO Collaborating Centre for Infectious Disease Modelling, MRC Centre for Global Infectious Disease Analysis, Imperial College London. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida- fellowships/Imperial-College-2019-nCoV-severity-10-02-2020.pdf Accessed February 11, 2020.
59. Shen KL, Yang YH. Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue. World J Pediatr. 2020.
60. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel noronavirus in the United States. N Engl J Med. 2020.
61. Yu IT, Li Y, Wong TW, et al. Evidence of airborne transmission of the severe acute respiratory syndrome virus. N Engl J Med. 2004;350:1731-1739.
62. Chen J. Pathogenicity and transmissibility of 2019-nCoV-A quick overview and comparison with other emerging viruses. Microbes Infect. 2020.
63. Haddad LB, Jamieson DJ, Rasmussen SA. Pregnant women and the Ebola crisis. N Engl J Med. 2018;379:2492-2493.
64. Chen H, Guo J, Wang C, 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; Published online February 12, 2020.
65. Zhu H, Wang L, Fang C, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr 2020.
66. Paules CI, Marston HD, Fauci AS. Coronavirus infections-More than just the common cold. JAMA. 2020.
67. Pacheco LD, Saade GR, Hankins GDV. Extracorporeal membrane oxygenation (ECMO) during pregnancy and postpartum. Semin Perinatol. 2018;42:21-25.
68. Lapinsky SE. Management of acute respiratory failure in pregnancy. Semin Respir Crit Care Med. 2017;38:201-207.
69. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for critically ill patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018;197:757-767.
70. D’Amore R. Can coronavirus pass from mother to baby? Maybe, but experts need more research. Global News. https://globalnews.ca/news/6515302/coronavirus-mother-baby- transmission/ Posted February 7, 2020. Accessed February 10, 2020.
71. Rasmussen SA, Kissin DM, Yeung LF, et al. Preparing for influenza after 2009 H1N1: special considerations for pregnant women and newborns. Am J Obstet Gynecol. 2011;204:S13-20.
72. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol. 2020.
73. CDC. Interim infection prevention and control recommendations for patients with confirmed 2019 novel coronavirus (2019-nCoV) or patients under investigation for 2019- nCoV in healthcare settings. Centers for Disease Control and Prevention. Updated February 3, 2020. https://www.cdc.gov/coronavirus/2019-nCoV/hcp/infection- control.html Accessed February 11, 2020.
74. CDC. Interim guidance for implementing home care of people not requiring hospitalization for 2019 novel coronavirus (2019-nCoV). Updated January 31, 2020 – https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-home-care.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019- ncov%2Fguidance-home-care.html. Accessed February 11, 2020
76. Steinbuch, Y. Chinese Baby Tests Positive for Coronavirus 30 Hours after Birth. Available online: https://nypost.com/2020/02/05/chinese-baby-tests-positive-for-coronavirus-30-hours-after-birth/ (accessed on 9 February 2020).
77. Woodward, A. A Pregnant Mother Infected with the Coronavirus Gave Birth, and Her Baby Tested Positive 30 Hours Later. Available online: https://www.businessinsider.com/wuhan-coronavirus-in-infant-born-from-infected-mother-2020-2 (accessed on 8 February 2020).
78. Gillespie, T. Coronavirus: Doctors Fear Pregnant Women Can Pass on Illness after Newborn Baby Is Diagnosed. Available online: https://news.sky.com/story/coronavirus-doctors-fear-pregnant-women-can-pass-on-illness-after-newborn-baby-is-diagnosed-11926968 (accessed on 8 February 2020).
79. Science Media Centre. Expert Reaction to Newborn Baby Testing Positive for Coronavirus in Wuhan. Available online: https://www.sciencemediacentre.org/expert-reaction-to-newborn-baby-testing-positive-for-coronavirus-in-wuhan/ (accessed on 9 February 2020).
