key: cord-311918-gifwg2ho
authors: BENDER, Whitney R.; HIRSHBERG, Adi; COUTIFARIS, Paulina; ACKER, Alexandra L.; SRINIVAS, Sindhu K.
title: Universal Testing for SARS-CoV-2 in Two Philadelphia Hospitals: Carrier Prevalence and Symptom Development Over Two Weeks
date: 2020-09-11
journal: Am J Obstet Gynecol MFM
DOI: 10.1016/j.ajogmf.2020.100226
sha: 
doc_id: 311918
cord_uid: gifwg2ho

Background The COVID-19 pandemic caused by the SARS-CoV-2 virus has challenged obstetric care providers. Universal testing on labor and delivery units has been implemented by many hospitals to ensure patient and staff safety. Asymptomatic carrier rates are expected to vary based on geographic differences in disease prevalence, although differences within the same city have not previously been reported. Additionally, clinical follow-up of women testing negative for SARS-CoV-2 during obstetric hospitalization have not been included in any prior reports. Objectives To describe the prevalence of positive SARS-CoV-2 tests among asymptomatic pregnant women at two Philadelphia obstetric hospitals, characterize the clinical course of those testing positive, and report symptom development among all women tested in the two weeks post-hospitalization. Study Design This is an observational study of asymptomatic pregnant women who underwent SARS-CoV-2 testing at two academic health centers (HUP and PAH) in Philadelphia, PA between April 13, 2020 and April 26, 2020. All women tested were contacted via telephone for symptom follow-up at one and two weeks post-discharge. Asymptomatic positive test rates are reported for the overall population and by hospital. The hospital and two-week post-hospital course are described for women testing positive for SARS-CoV-2. Post-hospital symptom development among women testing negative for SARS-CoV-2 is also described. Results Three hundred and eighteen asymptomatic women underwent SARS-CoV-2 testing during this two-week period. Eight women tested positive. The overall asymptomatic test positive rate was 2.5%. The rate at HUP was 3.8% compared to 1.3% at PAH (p = 0.283). Three women (37.5%) who were initially asymptomatic developed mild symptoms in the two weeks after positive test. Repeat SARS-CoV-2 testing was performed in 14 of the 310 women (4.5%) who initially tested negative; two women (0.6%) were positive on repeat testing. 242 (78.1%) and 213 (68.7%) of the 310 women who were SARS-CoV-2 negative at time of initial hospitalization were reached for telephone follow-up at one and two weeks post-admission, respectively. Viral symptoms, including fevers, chills, shortness of breath, or cough, were self-reported in 4.5% and 4.2% of these women at one and two weeks post-discharge, respectively. Conclusions The asymptomatic positive SARS-CoV-2 test rate among an obstetric population in Philadelphia differed between two hospitals and was lower than described in other geographic regions. This supports the importance of institution-specific testing protocols. The development of symptomatic SARS-CoV-2 infection post-hospitalization among women with initial negative testing is uncommon.

4 after positive test. Repeat SARS-CoV-2 testing was performed in 14 of the 310 women (4.5%) 77 who initially tested negative; two women (0.6%) were positive on repeat testing. 242 (78.1%) 78 and 213 (68.7%) of the 310 women who were SARS-CoV-2 negative at time of initial 79 hospitalization were reached for telephone follow-up at one and two weeks post-admission, 80

respectively. Viral symptoms, including fevers, chills, shortness of breath, or cough, were self-81 reported in 4.5% and 4.2% of these women at one and two weeks post-discharge, respectively. 82

The asymptomatic positive SARS-CoV-2 test rate among an obstetric population in 83

Philadelphia differed between two hospitals and was lower than described in other geographic 84 regions. This supports the importance of institution-specific testing protocols. The delivery, however, often cannot be delayed nor considered elective. 106

Due to the necessity of contact with the health system and the inability to delay such 107 contact, many hospitals have implemented universal testing for SARS-CoV-2 on labor and 108 delivery. Implementation of universal testing has raised many process-related questions 109 regarding isolation, use of personal protective equipment (PPE), accuracy of the test results and 110 implications for newborn and post-discharge care. Much of the information regarding universal 111 SARS-CoV-2 testing has focused on the obstetric population in New York City. The 112 asymptomatic positive rate has been reported as 13.5%. Symptom development occurred in 30-113 70% of women during the course of their hospitalizations or shortly thereafter. [1] [2] [3] [4] Geographic 114 differences in asymptomatic carrier rates have not been widely reported, although rates are 115 likely to be based on disease prevalence. To date, one additional report outside of New York 116 suggested lower asymptomatic SARS-CoV-2 test positive rate of < 3%. 5 117

In each of these studies, the follow-up period for asymptomatic test positive patients 118 was variable as delivery hospitalizations are typically short. Therefore, it remains unclear 119 whether these women were truly asymptomatic or pre-symptomatic. Further, no studies to 120 J o u r n a l P r e -p r o o f 6 date have reported follow-up of asymptomatic women who tested negative during their 121 hospitalization. 122

The objectives of this study are to describe the prevalence of positive SARS-Cov-2 tests 123 at time of admission for delivery among asymptomatic pregnant women in Philadelphia within 124 two large academic hospitals, characterize the in-hospital clinical course for those who tested 125 positive, and report the development of viral symptoms in all women tested for two weeks 126 after hospital discharge. 127

This is an observational study of pregnant women presenting for obstetric care at two 129 hospitals within a large academic health system in Philadelphia, Pennsylvania between April 13, 130 2020 and April 26, 2020. Given its retrospective nature, this study was deemed exempt by the 131 University of Pennsylvania Institutional Review Board. 132

All women presenting for delivery at the Hospital of the University of Pennsylvania 133 (HUP) and Pennsylvania Hospital (PAH) were approached for testing for SARS-CoV-2 via 134 nasopharyngeal and oropharyngeal swab as part of a universal testing clinical protocol. 135

Women admitted for other obstetrical indication and deemed likely to deliver during the 136 admission were also tested. Collection of these specimens was performed by physicians and 137 advanced practice providers at HUP and by registered nurses at PAH. All staff received hands-138 on training on specimen collection at the start of this clinical protocol. A real-time PCR assay 139 was performed for the qualitative detection of nucleic acid of the SARS-CoV-2 virus. Women 140 who reported viral symptoms, were febrile at the time of presentation, or had a known SARS-141

CoV-2 exposure were deemed persons under investigation and were excluded from this study 142 Test results, demographic, obstetric, and neonatal data were abstracted from the 160 electronic medical record (EMR) by a single investigator (WB). The development of viral 161 symptoms among those women who tested positive was also recorded. Telephone calls were 162 made to all of these patients at 7-9 days and 12-14 days post-hospital admission and test date 163 as part of routine clinical follow-up. A total of two weeks of follow up was obtained given the 164 J o u r n a l P r e -p r o o f 8 reported potential for gradual symptom onset over this time period. 6,7 During these calls, 165

patients were asked about the need for personal medical care or the development of viral 166 symptoms in themselves or their family since hospital discharge. The development of viral 167 symptoms was assessed using standardized scripting. Viral symptoms included in the standard 168 script were fever, shortness of breath, anosmia, cough, headaches, sore throat, rhinorrhea, 169 nausea, vomiting, diarrhea, and muscle aches. 170

Sample size was fixed based on the number of women admitted during the prespecified 171 timeframe. Descriptive statistics were calculated for the population at large. Comparisons were 172 made between hospitals and between women testing positive and negative for SARS-CoV-2. 173

The association of categorical variables with binary outcomes were analyzed using Fisher exact 174 test or chi squared analyses as appropriate. The associations of continuous variables with 175 binary outcomes were analyzed using student's t-test or Wilcoxon rank-sum tests for non-176 normally distributed variables 177

During the specified two-week timeframe, testing was not completed on seven women 179 across both sites. Three hundred and eighteen women were tested for SARS-CoV-2; 160 were 180 tested at HUP and 158 were tested at PAH. 181

Complete demographic data for the population by hospital site is listed in Table 1 . Of 182 note, black women accounted for 43% of the total population. Women delivering at PAH were 183 less likely to be black or publically-insured. 9 between the two hospitals. Six women (3.8%) were positive for SARS-CoV-2 at HUP compared 187 to only 1.3% (2/158) of women testing positive for SARS-CoV-2 at PAH (p = 0.283). 188

As seen in Table 2 , there were no differences in demographic characteristics or delivery 189 outcomes between asymptomatic women with positive and negative SARS-CoV-2 test results. 190

Seven of the eight women who tested positive for SARS-CoV-2 were without medical 191 comorbidities; one woman had chronic hypertension. Details of the hospital course for the 192 eight asymptomatic women with a positive SARS-CoV-2 test are shown in Table 3 . Six women 193 delivered a full-term living neonate, with negative SARS-CoV-2 testing on all of these infants. 194

One woman was discharged undelivered after a trauma observation. CoV-2 during their admission. Repeat testing was performed for 14 patients as shown in Table  210 4. Repeat testing was done on the index hospitalization for an unexplained fever on postpartum 211 day one for one patient and again resulted negative. Another patient had repeat testing prior to 212 delivery four days after initial admission testing. The remaining 12 repeat tests were performed 213 at either a subsequent emergency evaluation or hospital readmission. 

In this retrospective cohort study, the asymptomatic SARS-COV-2 test positive rate 248 among pregnant women in Philadelphia was 2.5%. However, it is important to note that the 249 asymptomatic test positive rates differed between the two hospitals (3.8% v. 1.3%) despite only 250 four miles separating the two sites. Eight asymptomatic women tested positive, only one of 251 whom developed a fever during the hospitalization; the other seven remained asymptomatic 252 12 during their hospitalization. None of the women required additional care during the two week 253 follow up period. In addition to the patient who developed a fever while in the hospital, two 254 women subsequently developed mild symptoms within one week of being tested. Therefore, 255 five of the eight women (62.5%) with positive SARS-CoV-2 testing remained asymptomatic. 256

Women who tested negative for SARS-CoV-2 were also followed for two weeks post-257 hospitalization. Two women developed fever and respiratory symptoms during this timeframe 258 and were diagnosed with COVID-19 on repeat testing; in both cases, this occurred more than 5 259 days after initial negative test. 260

This study adds to the growing body of literature on asymptomatic testing for SARS-CoV-262 2 in the obstetric patient. Our rate of asymptomatic positive tests is lower than reported for 263 similar programs in New York City, likely secondary to differences in local disease prevalence. 264

Additionally, the development of symptoms in our asymptomatic test positive population (3/8; 265 37.5%) is lower than that described in the New York City cohort (over 70%). 2 266

Interestingly, however, two hospitals within the same city and health system had 268 clinically though not statistically different asymptomatic positive test rates during the same 269 time frame. The reason for this difference could be several fold. Although all providers received 270 similar instructions on specimen collection, testing was performed by different personnel at 271 each site. Additionally, there are some notable differences in patient population. The difference 272 in rates despite close proximity of the hospitals supports the need for institution-driven testing 273 rather than reliance upon regionally or nationally-reported information. 274 J o u r n a l P r e -p r o o f 13 The inclusion of follow-up data from SARS-CoV-2 negative women allows us to comment 275 upon the potential for false negative test results, negative test results during a potential 276 presymptomatic period, or the risk of viral acquisition during hospitalization. Less than 1% 277

(2/310) of women developed SARS-CoV-2 during their two-week follow-up. While we cannot 278 ascertain when or how these infections were acquired, the low rate of symptomatic infection 279 following discharge may be useful for counseling and providing reassurance to women who 280 have anxiety about disease exposure during their delivery hospitalization throughout the 281 pandemic. While an additional 4-5% of women reported viral symptoms including chills, 282 shortness of breath, or cough in the two-week follow-up period, none of these women were 283 tested for SARS-CoV-2 infection. Therefore, the true significance of these symptoms remains 284 unknown. Five of the eight women who tested positive for SARS-CoV-2 remained asymptomatic 285 during the two week follow-up period. Repeat testing was not performed routinely in this 286 population in the 2 weeks post-delivery, and as such, the possibility for false positive test 287 results cannot be adequately addressed with the data available. 288

As additional testing becomes available, future research is needed to determine the true 290 significance of any viral symptoms post-hospitalization. As this study is among the first to report 291 clinical follow-up from asymptomatic negative women, additional studies are warranted to 292 confirm its findings. Further work to confirm geographic variations within cities and investigate 293 the reasons for their existence is also warranted. Lastly, additional studies are warranted to 294 determine the impact of universal SARS-CoV-2 testing on population spread as well as patient 295 and provider anxiety. 296

This study has several strengths. This was a large cohort study of all asymptomatic 298 pregnant women presenting for care at two hospitals in an academic health system. Data 299 describing hospitalization was abstracted by a single author. The inclusion of telephone-call 300 derived data until two-weeks post-hospitalization for both SARS-CoV-2-positive and negative 301 women allows us to comment upon symptom development in both populations. 302

This study is not without limitations. As this study was conducted within a single 303 academic health system, the data may not be generalizable to the population at large. Follow-304 up information regarding interval symptom development was based on patient report. 305

However, this is the most accurate way to comprehensively assess this information. Lastly, the 306 vast majority (95%) of patients were not re-tested in a short interval to determine conversion of 307 asymptomatic test negative patients to test positive. This is particularly important for the 4.5% 308 and 4.2% of women who reported viral symptoms at one and two weeks postpartum, 309 respectively. Seroconversion of these women to SARS-CoV-2 positive would not have been 310 noted given they did not all undergo repeat SARS-CoV-2 testing. Therefore, it remains possible 311 that the rate of infection development post-hospitalization is higher than the reported less than 312 1% in this cohort. If these were true SARS-CoV-2 infections, however, they were likely mild in 313 nature. Overall, the absence of development of symptoms in the vast majority of women (95%) 314 during the two weeks postpartum is reassuring. 315

In summary, this retrospective cohort study found an asymptomatic carrier rate ranging 317 from 1.3% to 3.8% in the Philadelphia obstetric population. The differences found between the 318 15 two hospitals highlights the importance of institution-specific information and approaches to 319 universal testing and PPE protocols. Less than 1% of the test negative women developed SARS-320

CoV-2 in the two weeks following hospitalization. This information may be an important 321 component of provider counseling as obstetricians continue to determine the best means of 322 providing high quality care in the pandemic. 323 324 J o u r n a l P r e -p r o o f 

Universal Screening for SARS-CoV-2 in Women 327

Admitted for Delivery

Coronavirus disease 2019 infection among asymptomatic and symptomatic pregnant 330 women: two weeks of confirmed presentation to an affiliated pair of New York City 331 hospitals

Critical Illness Among Obstetric Patients with Coronavirus Disease

Online 335 ahead of print

Outcomes of 241 Births to Women with Severe Acute Respiratory Syndrome 338

Coronavirus 2 (SARS-CoV-2) Infection at Five New York City Medical Centers

Online ahead of print

Clinical findings in a group of 346 patients infected with the 2019 novel coronavirus (SARS-CoV-2) outside of Wuhan

China: retrospective case series

The authors report no conflicts of interest. The authors have no financial disclosures to report.