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Our take —

The degree of immunity acquired by individuals after SARS-CoV-2 infection, and how it changes over time, is a matter of considerable public health concern. In contrast to a previous study showing rapidly waning levels of antibodies that target a different SARS-CoV-2 antigen among patients with mild symptoms, this study from New York City shows that neutralizing antibodies to SARS-CoV-2 spike protein diminished over time but remained at high levels up to 3 months after symptom onset in a group of patients with mostly mild illness. The patient population was small and not well described, so it is unclear if these results apply to the broader population of those infected with SARS-CoV-2. Important questions remain about how varying levels of SARS-CoV-2 antibody translate to protection from infection.

Study design

Case series; prospective cohort; other

Study population and setting

This paper reports on three related studies: 1) Enzyme linked immunoassay (ELISA) testing for IgG antibodies to the SARS-CoV-2 spike protein among 72,401 individuals with laboratory-confirmed or suspected infection approximately 30 days after symptom onset from the Mount Sinai Health System in New York City, from March to October 6, 2020; 2) testing of 120 samples that had a known ELISA titer for neutralization of SARS-CoV-2 using a quantitative neutralization assay; and 3) longitudinal screening of 121 patients for IgG antibodies to the SARS-CoV-2 spike protein at two additional time points (approximately 82 and 148 days after symptom onset) after the initial screening (approximately 30 days after symptom onset).

Summary of Main Findings

Less than 5% of all individuals screened required hospitalization or emergency room evaluation. Of those screened, 30,082 (42%) tested positive for detectable antibodies to the SARS-CoV-2 spike protein at a titer of 1:80 or higher. Most of those testing positive had moderate-to-high titers (defined as 1:320 or higher): 2.3% had a titer of 1:80, 4.8% of 1:160, 22.5% of 1:320, 31.8% of 1:960, and 38.6% of 1:2880. Neutralizing titers significantly correlated with ELISA titers (Spearman’s r=0.87). Half of sera with spike-binding titers between 1:80 and 1:160 had neutralizing activity, while 90% of sera with 1:320 titers and all those with 1:960 titers or above had neutralizing activity. Among the 121 individuals sampled over a total of three time points (at an average of 30, 82, and 148 days post-symptom onset), the geometric mean titers (GMT) declined from 764 to 690 to 404. Among those with a 1:320 titer or lower, antibody titers increased on average at the second time point, followed by a decrease at the third time point. Three individuals with initially low titers (1:80) lost reactivity, one at the second time point and two at the third. The correlation between neutralizing and ELISA titers remained high at the third time point (r=0.79).

Study Strengths

This study examined antibodies to the spike protein of SARS-CoV-2, which are likely to be more relevant to immunity than antibodies to nucleoprotein. Antibody titers were measured in a large number of individuals using an assay with high accuracy in a validation panel. Longitudinal analyses of antibody titers considered two time points after the initial assay, allowing for discernment of nonlinearities in trajectory.

Limitations

Patient demographic and clinical characteristics were not reported, which makes it difficult to interpret how these data apply to any particular group of individuals. Of particular concern is the lack of data on COVID-19 clinical severity in either the larger study population or in the two substudies. Thus, while it appears that these studies were conducted on primarily mild cases of COVID-19, this study did not assess any relationship between disease severity and antibody response. Also, the timing of initial antibody screening relative to symptom onset or date of potential exposure was not characterized in the larger study population and there was variation in the timing of antibody assays in the longitudinal study. Not all individuals screened for antibodies were tested for SARS-CoV-2 infection, which means an unknown number of people who had been infected with SARS-CoV-2 may have tested negative for antibodies. The size of the population in the longitudinal study (n=121) and the lack of reported demographic or clinical characteristics makes it difficult to generalize the results.

Value added

This study provides some of the strongest evidence to date regarding the persistence of neutralizing antibodies to SARS-CoV-2 over time, particularly among those without severe disease. This has implications for both pandemic planning and vaccine development.

Our take —

This case series provides a characterization of the first 100 cases of confirmed COVID-19 in Zambia, a lower-middle income country in sub-Saharan Africa, and includes a description of the national response in the early days of the pandemic. While this study documented known risk factors for disease (male sex), cases were generally young and only 20% had underlying comorbidities. Of those with comorbidities, HIV infection and hypertension were the most common. This study profiles Zambia’s experience in the early stages of the COVID-19 epidemic; however, updated data on the progress of their detection and containment strategies are warranted.

Study design

Case Series

Study population and setting

This case series details the likely source of infection, natural history, and clinical outcomes from the first 100 individuals with laboratory-confirmed SARS-CoV-2 infection in Zambia from March 18 to April 28, 2020. During this time frame, the Ministry of Health conducted 6,165 SARS-CoV-2 tests, initially only in individuals with suspected COVID-19, per the March 20, 2020 World Health Organization definition, and starting April 13, 2020 followed a national mandate, more broadly in all hospitalized patients, outpatients with fever, cough, or shortness of breath, any death in an individual with respiratory symptoms, and biweekly in healthcare workers in facilities that had treated any patients with COVID-19. Other measures to capture suspected cases included community-based and port-of-entry screening, a national public hotline, and contact tracing. From March 20 onwards, authorities in Zambia closed all schools, colleges, and universities, restricted foreign travel, and restricted mass gatherings to limit the spread of COVID-19.

Summary of Main Findings

Of the 6,165 tests, 100 (1.6%) were positive. Most positive tests (77%) were from Lusaka, and were identified through point-of-entry testing (35%) or contact tracing (30%). The majority of cases were males (61%) and in those 30 to 44 years of age (32%). At the time of testing, most cases were asymptomatic (79%); among those with symptoms, fever, cough, sore throat, headache and fatigue were the most common. Patients recovered a median of 12 days (interquartile range 1-42 days) from symptom onset (or date of testing for asymptomatic patients). Although few patients (20%) had comorbidities, those who did were most likely to have HIV (35%) or hypertension (35%). All three patients who died (3 out of 100 cases) had at least one underlying health condition and two of them received intensive care services.

Study Strengths

This study provides detailed epidemiologic and clinical data on the first 100 cases of COVID-19 in Zambia.

Limitations

This case series does not offer insight into how COVID-19 may have acted and/or spread in Zambia after these first 100 cases, particularly how its dynamics may have changed as the virus spread beyond the capital city (Lusaka). Additionally, these data are not necessarily representative of other countries in the region.

Value added

This is one of the first characterizations of how one country in sub-Saharan Africa (Zambia) tracked and managed the first 100 cases over the first 41 days of the COVID-19 pandemic within its borders.

Our take —

Using detailed epidemiologic, contact tracing, and genome sequencing data, a cluster of infections was identified with an apparent source of an indoor bar in Ho Chi Minh City on March 14, 2020. From the initial index case, a total of 18 additional cases were identified, including 12 who also attended the bar that evening. This event was characterized as a superspreading event, and genome sequencing data confirms these clusters as likely being part of the same, single cluster. Without adequate precautions, indoor bars with poor ventilation and prolonged contact between patrons may be the site of superspreading events.

Study design

Case Series

Study population and setting

This study presents findings on an identified case of COVID-19 in Ho Chi Minh City, Vietnam on March 18, 2020 and the contact tracing data related to this case. The contact tracing data identifies a likely superspreading event, defined as between six and eight secondary cases. Genetic sequencing was conducted in order to further establish whether the identified cases were from the same cluster.

Summary of Main Findings

The index patient was a 43-year old man who presented to the Hospital for Tropical Diseases with fever, cough, and other symptoms. Symptom onset was on March 17, 2020. He subsequently showed evidence of SARS-CoV-2 infection by RT-PCR. Based on the contact tracing data, the index patient had traveled between Thailand and Vietnam in the 14 days prior to symptom onset. He had attended an event at an indoor bar in Ho Chi Minh City on March 14. Based on contact tracing data, an additional 18 positive PCR-confirmed cases were identified (12 from the bar and 6 were other contacts). None of the confirmed cases reported any symptoms on March 14 or 15. Whole genome sequences of SARS-CoV-2 obtained from 11 of the confirmed cases were either identical of very similar, even when compared with other sequences from Ho Chi Minh City.

Study Strengths

Detailed contact tracing data and sequencing data provide strong evidence of a superspreading event that took place in an indoor bar.

Limitations

The total number of contacts of the initial case is not provided and therefore calculation of a secondary attack rate is not possible.

Value added

Results from this study provide further evidence that indoor bars with limited ventilation may be the site of superspreading events.

Our take —

Several CDC case reports and published case series suggest that multisystem inflammatory syndrome due to SARS-CoV-2 infection may not be limited to children. This MMWR describes 27 cases of MIS-A (adults) who had confirmed SARS-CoV-2 infection (either previously or currently) and were hospitalized with severe dysfunction of extrapulmonary organ systems but minimal respiratory illness. However, the clinical presentation, timing, and ascertainment of SARS-CoV-2 infection varied widely, and refinements to the MIS-A case definition will help to estimate the overall burden of disease and guide research on its pathogenesis.

Study design

Case Series

Study population and setting

This report describes 27 patients with multisystem inflammatory syndrome in adults (MIS-A) from three data sources: CDC reports (n=9), published case reports (n=7), and three published case series (n=11). MIS-A was defined as adults (21+ years) who were hospitalized with severe illness, had a positive test result for SARS-CoV-2 during admission or in the prior 12 weeks, had severe dysfunction of at least other extrapulmonary organ system, had laboratory evidence of severe inflammation, and did not have severe respiratory illness. The cases were voluntarily reported to CDC by clinicians and health departments using a case report form developed for MIS-C (multisystem inflammatory syndrome in children). A literature search on August 20, 2020 identified the additional published case reports and case series.

Summary of Main Findings

Among the 16 patients (56% women, age range: 21-50 years, 56% with underlying conditions) included in case reports (9 from CDC reports and 7 from published case reports), all had evidence of cardiac involvement, 13 had GI symptoms at admission, and 10 had evidence of pulmonary involvement despite minimal respiratory symptoms. Inflammatory markers (CRP and ferritin) and markers of coagulopathy (D-dimer) were elevated in all. Timing of SARS-CoV-2 testing was variable; only 10 showed evidence of SARS-CoV-2 by RT-PCR at initial assessment for MIS-A, 4 had positive antibody tests at admission, and 2 were positive 14 and 37 days prior to admission but were negative at the time of admission. Ten required intensive care, and two patients died. Data from the published case series (n=11 from 3 case series) were similar: age range 20-50, at least four with negative PCR tests at admission but high IgG antibody titers, elevated inflammatory markers, and heterogeneous presentation (two patients had large vessel strokes, others with cardiac dysfunction, GI symptoms, and dermatologic symptoms, but mild respiratory symptoms).

Study Strengths

The report includes a thorough review of MIS-A cases in the United States and the United Kingdom.

Limitations

Given that this was a case series of voluntarily reported cases to CDC and published case series/reports, the results likely do not capture all MIS-A cases in the US or the UK during this time frame, and also cannot be used to estimate the overall burden of MIS-A in the US or UK population. The case definition included required participants have evidence of SARS-CoV-2 with a current or previous positive result on either PCR, antigen, or antibody tests. It’s possible that some patients with MIS-A related symptoms never received testing for SARS-CoV-2, which could have resulted in exclusion of some cases. The timing of SARS-CoV-2 infection and MIS-A is still unclear and cannot be adequately inferred from this data.

Value added

There have been several well-described reports of MIS-C, but this is one of the most comprehensive reports of MIS-A in the United States and the United Kingdom.

Our take —

In the late summer, 14 individuals from four different states and five households came together for a three-week family gathering. From a single asymptomatic, adolescent index case, 11 more individuals were infected and developed COVID-19, including 85% of those staying in the same house over this period. Though the index case had a known exposure and sought testing and received a negative rapid antigen test prior to attending the family event, transmission of SARS-CoV-2 during this gathering still occurred. This study provides an empirical reminder that transmission at family gatherings is possible even when index cases are young, asymptomatic and have had a negative test. A negative rapid test is not confirmation that transmission will not happen given variabilities in sensitivity of diagnostics as well as the extended incubation period of the virus. Eliminating indoor contact, exposure times, mask wearing and physical distancing appeared to have reduced risk in this situation. As we approach the holidays, these data should be used to inform multi-household gatherings.

Study design

Case Series

Study population and setting

In this study, an outbreak during a three-week family gathering of five households from four different states between July and August 2020 was investigated. The index case was a thirteen-year-old adolescent and had a known exposure in June 2020. Because of this exposure, the index case sought out testing four days after exposure and tested negative to a rapid antigen test. Detailed demographic characteristics, exposures, symptoms, close contacts, and outcomes were obtained from this family gathering and analyzed. Viral testing was completed among all those staying together during this period and antibody testing was completed on those who were not tested while symptomatic.

Summary of Main Findings

Attendees of the family gathering ranged in age from 9 to 72 years old. Overall, the outbreak directly affected the asymptomatic adolescent index case and 11 of the 19 family members. Of the 13 relatives of the index case who were staying together in a house during this period, 11 (84.6%) of them experienced symptoms and subsequently developed COVID-19. Three individuals, including the index case and her two brothers, tested positive for antibodies, suggesting earlier infection. While eight individuals reported participating in activities that may have increased their risk during this period, only the index case had confirmed contact with a known case. An additional six relatives visited, but did not stay, maintained physical distance, and remained outdoors. Of the four visiting relatives tested, all four tested negative by RT-PCR.

Study Strengths

Nearly complete exposure, symptom, contacts, and testing data allow for a detailed investigation of this outbreak at a family gathering.

Limitations

Because attendees of this family gathering did have contact with individuals outside of this group during this same period, an external source of transmission cannot be ruled out, though the evidence supports the hypothesis that the supposed index patient is in fact the source of the outbreak.

Value added

This investigation is a timely reminder, given the upcoming holiday season, of the potential for transmission between family members at planned gatherings where mask use and physical distancing are not utilized. Importantly, these results highlight that children and adolescents can serve as the source for outbreaks regardless of whether or not they have symptoms.

Our take —

This study reported a high positivity rate of SARS-CoV-2 testing among neonates (aged 0-28 days) in serious condition at a referral center in Bangladesh. Six of the 8 babies who died had serious comorbidities that are commonly seen in neonates in low and middle-income countries (LMICs). Although half of the cases were identified within the first 5 days after birth, many neonates suffered from delays or gaps in treatment. In some cases, these delays were caused by the COVID-19 diagnosis itself, because the pediatric referral center was not equipped with adequate infection control procedures to perform necessary treatment. This study highlights the amplified risks of SARS-CoV-2 infection for distressed neonates in LMICs.

Study design

Case Series

Study population and setting

This study reports on 26 neonates (aged 0-28 days, median age 8 days, 62% male) with laboratory-confirmed SARS-CoV-2 infection who were admitted to the largest pediatric referral hospital in Bangladesh, from March 29 to July 1, 2020. Neonates with confirmed infections were transferred to designated COVID-19 care hospitals for further treatment. Demographic and clinical data were collected prospectively with standardized forms. Outcomes were assessed via standardized telephone questionnaires through July 28, 2020.

Summary of Main Findings

Of 83 neonates tested, 26 (31%) were positive for SARS-CoV-2 infection. All neonates were born at term. Half were referred to the hospital and identified as COVID-19 cases within the first five days after birth. Four babies died before leaving the hospital. Of the 22 babies who left the hospital alive, 19 were followed up for outcomes; follow-up time for those who did not die ranged from 8 to 102 days. Four babies died during follow-up, 3 required continuing medical care, and 12 recovered. Seven babies initially presented with symptoms of early onset neonatal sepsis (EONS), while 5 had clinical signs of late onset neonatal sepsis (LONS). Two babies presented with pneumonia; one died, while the other was lost to follow-up. Eleven neonates had serious non-communicable diseases at admission, including ruptured myelomeningocele, anocutaneous fistula, ruptured occipital encephalocele, anorectal malformation, obstructive uropathy, and congenital heart disease. Of the 8 babies who died, 6 had serious comorbidities. Among the 9 immediate caregivers (8 mothers and one grandmother) who were tested for SARS-CoV-2 infection at time of neonate specimen collection, 8 tested positive. Among the 11 other mothers who were not tested but who were interviewed, 2 reported symptoms consistent with COVID-19 in the days before delivery.

Study Strengths

This study reported on a substantial number of cases relative to previous reports of SARS-CoV-2 infection in neonates. A large number of clinical and laboratory parameters were measured and reported.

Limitations

Neonates were transferred to another facility because of their COVID-19 status and three were lost to follow-up. Cases were limited to those in serious condition, since they were drawn from a referral center; thus, the cases were at high risk of death and no asymptomatic or mild cases were detected. Maternal SARS-CoV-2 infection status was only assessed for a subset (8/26) of neonates. X-rays (5/26) and other laboratory tests were only performed on a limited number of patients. Follow-up duration was not sufficient to assess incidence of longer-term sequelae such as multisystem inflammatory syndrome in children (MIS-C).

Value added

This is among the largest reported case series of neonatal SARS-CoV-2 infection, and the first from the South Asian region and a low and middle-income country.

Our take —

In this case series of 509 patients hospitalized in Chicago with COVID-19, neurologic manifestations were common (e.g. myalgias, headache, dysgeusia, anosmia, encephalopathy): 42% of patients had at least one at symptom onset, and 82% experienced one at any time during COVID-19. The only neurologic manifestation associated with clinical outcomes was encephalopathy. More research into the causal relationship between neurologic symptoms and COVID-19 outcomes, and on the long-term effects of neurologic manifestations during COVID-19 are needed.

Study design

Case Series, Retrospective Cohort

Study population and setting

This study tested the association of neurologic manifestations of COVID-19 with clinical outcomes among 509 hospitalized patients with PCR-confirmed SARS-CoV-2 infection, who were consecutively admitted to one of the ten centers within the Northwestern Medicine Healthcare system in Chicago from March 5 to April 6, 2020. Data on demographics, comorbidities, disease course, and labs were extracted from electronic medical records. COVID-19 disease severity was defined as severe vs. non-severe, based on need for any mechanical ventilation during hospitalization. Neurologic manifestations were considered from symptom onset though 90 days. The main outcome of interest was functional outcome at hospital discharge, defined by the modified Rankin Scale (mRS) with a range from 0 (able to look after oneself without assistance) to 6 (death).

Summary of Main Findings

Among 509 patients hospitalized with COVID-19 (mean age 58.5 years, 55% male, 26% with severe disease), 42% had neurologic manifestations at COVID-19 onset, 63% at hospital admission, and 82% at any time during disease course. At COVID-19 onset, the most frequent neurologic manifestations were myalgia (body aches), headache, and dysgeusia (distortion of taste), experienced by 26%, 17%, and 5% of people, respectively. At any time during the clinical course, 45% of participants had myalgia, 38% had headache, 32% had encephalopathy (altered mental status, confusion, depressed level of consciousness), 30% experienced dizziness/vertigo, and 16% had dysgeusia. Other than encephalopathy, which was considerably more common among individuals with severe COVID-19 (84% vs. 13% in non-severe cases), the distribution of neurologic manifestations were similar between severe and non-severe patients. Encephalopathy was the only neurologic outcome associated with worse favorable outcome and greater mortality, after adjusting for a range of covariates including COVID-19 severity, sex, history of neurologic disorder, time from COVID-19 onset to hospitalization, academic medical center hospitalization, and race.

Study Strengths

Neurologic manifestations and functional outcomes were decided by consensus of two independent reviewers.

Limitations

This study does not demonstrate that encephalopathy is a cause of poor clinical outcomes; for example, it is possible that clinical deterioration due to COVID-19, or therapies received during hospitalization, caused encephalopathy. A broad range of neurologic manifestations were considered, which have differing severity and role in clinical presentation and outcomes; considering them all together may hide heterogeneities in specific manifestations. Fewer than 6% of patients were evaluated by neurologists or neurosurgeons, so it is possible that neurologic manifestations were under- or mis-reported. Additionally, assessing temporality is limited by self-report of symptoms present at time of COVID-19 onset (i.e., it is unknown whether neurologic symptoms preceded COVID-19 diagnosis). The study included multiple sites in the Chicago area but only included hospitalized patients; thus, the degree to which the results are generalizable to other populations, including those with mild disease, is unclear. The study did not examine long-term consequences of these neurologic manifestations.

Value added

This relatively large and multi-site case series is one of the few studies to specifically examine neurologic symptoms as a predictor of disease severity.

Our take —

This case series followed 49 patients with a history of kidney transplant who contracted COVID-19 in Alsace, France at the beginning of the pandemic. No patients lost their grafted kidneys, but 9 patients died. High levels of all measured inflammatory markers were significantly associated with mortality. Though limited by its small sample size, lack of a control group, and variable treatment strategies, this study is a starting point for research on the impact of COVID-19 among individuals with kidney transplant.

Study design

Case Series

Study population and setting

This case series followed 49 patients with a history of kidney transplantation who presented to a hospital in Alsace, France between March 4 and April 7, 2020 with evidence ofSARS-CoV-2 infection by PCR, imaging consistent with COVID-19, and/or high clinical suspicion for COVID-19. Medical record data were collected daily from admission and included demographics, COVID-19 presentation, laboratory values, medications, and imaging until April 30, 2020. The authors were primarily interested in the following predefined outcomes: death, intensive care unit admission, acute kidney injury, graft loss, venous thrombotic events, and neurologic or cardiac complications. Patients were categorized with 1) mild COVID-19 (outpatient), 2) non-severe COVID-19 (hospitalized with <6L/min supplemental oxygen), and 3) severe COVID-19 (hospitalized and > 6L/min supplemental oxygen), and continuous covariates were tested for association with these outcomes using Mann-Whitney tests and Spearman’s correlation coefficients. Finally, the authors analyzed time to severe COVID-19 and time to COVID-19 death using Kaplan-Meier curves among hospitalized patients with non-missing data. Log-rank tests were used to compare estimated survival for patients with different dichotomized values of c-reactive protein, interleukin-6, lactate dehydrogenase, high sensitivity troponin, D-dimer, and fibrinogen. Receiver operating characteristic (ROC) curves were based on dichotomized levels of these biomarkers.

Summary of Main Findings

The median time between kidney transplant and COVID-19 symptom onset among the 49 included patients was 7.1 years (interquartile range 2.9-14.4 years). Most patients were white (98%), male (76%), and/or over 60 years (55%). The 8 patients with mild COVID-19 were, on average, younger, had a lower median body mass index, and were more likely to be treated with mTOR inhibitors than the 41 hospitalized patients (21 non-severe, 20 severe). A majority of hospitalized patients were obese (51%). On admission, mycophenolate mofetil/mycophenolic acid and mTOR inhibitors were discontinued, and calcineurin inhibitors were temporarily withdrawn in 15 (36.6%) patients. Among all hospitalized patients, there were no graft failures, 14 (34%) patients were admitted to the intensive care unit, 16 (39%) experienced mild-to-severe neurologic complications, 1 experienced deep vein thrombosis, 1 experienced myocarditis, 31 (76%) experienced acute kidney injury (23 of whom recovered), and 9 (22%) patients died. Patients with severe COVID-19 were more likely to be obese, to have shortness of breath rather than diarrhea, and to have lower arterial oxygen levels and higher c-reactive protein, interleukin-6, and high sensitivity troponin on admission. High levels of all measured inflammatory markers were significantly associated with mortality via the log-rank test.

Study Strengths

This study focused on an understudied population during the COVID-19 pandemic: those with a history of a kidney transplant.

Limitations

This study was limited by its small sample size and a lack of a control group, which makes it hard to generalize to other individuals with a history of a kidney transplant, and precludes comparison with other COVID-19 patients. Almost by definition, patients with a history of kidney transplantation have a complicated medical history that may include diabetes, obesity, hypertension, and other comorbidities, which makes it difficult to home in on the added COVID-related risks posed by a grafted kidney and the necessary chronic immunosuppression. Furthermore, since this study was conducted early in the pandemic, participants received a wide variety of treatments, most of which have since been found ineffective against COVID-19 in large randomized trials. This makes it difficult to assess how individuals with a history of a kidney transplant might fare if they contracted COVID-19 at a later date. Finally, the authors dichotomized laboratory values to create Kaplan-Meier curves, which likely results in residual confounding.

Value added

This study provides some insight into the implications of COVID-19 for patients with a history of a kidney transplant. Importantly, none of the included patients lost their grafted kidney.

Our take —

This descriptive study of 105 pregnant women hospitalized with COVID-19 at eight U.S. surveillance sites demonstrated a significantly higher risk profile among pregnant cases admitted for non-obstetric reasons compared to those hospitalized for obstetric reasons, underscoring the need to consider the relative proportion of these sub-populations when interpreting and comparing hospital-based studies of COVID-19 in pregnancy. Though preterm birth and stillbirth were more prevalent among this small sample of pregnant women with COVID-19 than among all births at the facilities, this study does not establish whether this crude difference may be attributable to COVID-19 or to higher levels of other established risk factors among those with COVID-19 (e.g. 10% of the sample had a history of preterm birth).

Study design

Case Series

Study population and setting

This study used data from the US Vaccine Safety Datalink surveillance system to describe the characteristics and outcomes of pregnant women hospitalized with COVID-19 in 8 health care systems. Among the 4,408 people hospitalized with COVID-19 at surveillance sites from March 1 to May 30, 2020, 105 were pregnant (median age 30 years; 62% Hispanic/Latina; median gestational age 38 weeks). Data were abstracted from medical records and the reasons for hospital admission were adjudicated by a physician.

Summary of Main Findings

During the study period, 41% (43) of the pregnant women were hospitalized for COVID-19 without an obstetric indication, while the remaining 59% (62) were admitted for labor or other obstetric reasons. Among the latter, 80% (50) were asymptomatic. Compared to the women hospitalized for obstetric reasons, women hospitalized for COVID-19 were earlier in pregnancy, had a higher prevalence of pre-pregnancy obesity and gestational diabetes, and accounted for all but one Intensive Care Unit admission. Overall, 14 (15%) of the 93 women with completed pregnancies delivered preterm (labor was induced because of respiratory distress in 3 of these cases), and there were 3 (3%) stillbirths, one with placental abruption and two without known etiology. The prevalence of preterm birth and stillbirth were similar regardless of indication for hospitalization or the presence of symptoms but were higher than the overall prevalence at the same facilities among all pregnant women in the Vaccine Safety Datalink surveillance system during the same period of 8.9% preterm birth and 0.6% stillbirth.

Study Strengths

The reason for hospital admission was adjudicated by a clinician, enabling the authors to appropriately stratify outcomes and characteristics of pregnant women with COVID-19. There was much less data missing for this sample in comparison to previous studies of COVID-19 in pregnancy using other surveillance systems. This allowed the authors to characterize important risk factors for COVID-19 severity and adverse birth outcomes for all 105 pregnant women hospitalized with COVID-19 at the surveillance sites during the study period.

Limitations

The study did not include a comparison group of pregnant women without COVID-19 to evaluate whether COVID-19 was associated with adverse birth outcomes. The surveillance system captured a relatively small number of pregnant women, and it is unclear how the population at the surveillance sites compares to the population of pregnant women in the US.

Value added

This study documented that pregnant women with COVID-19 who are hospitalized for non-obstetric reasons differ significantly from cases who are hospitalized for obstetric reasons, with the former group including more women in earlier stages of pregnancy, having a higher prevalence of underlying and gestational comorbidities, and a higher prevalence of COVID-19 disease severity. COVID-19 screening policies in antenatal and maternity care have varied between health systems and over time, and many existing studies of COVID-19 in pregnancy have been unable to differentiate between these subpopulations.

Our take —

This descriptive study compared characteristics and outcomes among hospitalized pregnant women with COVID-19 with and without symptoms. The high proportion of asymptomatic cases suggests that, in many areas of the US, asymptomatic pregnant women are screened for COVID-19 prior to delivery and have good pregnancy outcomes. While the finding that pregnancy loss and preterm birth outcomes were more common among symptomatic compared to asymptomatic women adds to our knowledge and fits with previous disease severity data, the absolute levels and comparisons were not adjusted for other salient risk factors that may differ between groups. The sample size and geographic and racial/ethnic diversity suggests trends that can be further explored with prospective studies that measure how infection with SARS-CoV-2 impacts pregnancy outcomes in the United States.

Study design

Case Series, Cross-Sectional

Study population and setting

The authors used data from a population-based surveillance system of COVID-19-related hospitalizations in 14 states (COVID-NET), 13 of which were included in this study. The surveillance system includes all patients in the catchment area who tested positive for SARS-CoV-2 during or in the 14 days before hospitalization for any reason. This study sample was drawn from a subset (2,318 of 7,895 total records of women aged 15-49 years who were hospitalized with COVID-19) whose data was systematically abstracted from medical records by trained surveillance officers. Among this subset, 26% were pregnant. This study included 529 pregnant women, aged 15-49 years, with laboratory-confirmed SARS-CoV-2 who were hospitalized between March 1 and August 22, 2020.

Summary of Main Findings

The majority of pregnant women were aged 25-34 years, the majority (87%) were in their third trimester, Black and Hispanic women were overrepresented as compared to the catchment area (comprising 26.5% and 43% of the sample, respectively), and 20.6% had at least one other medical condition. Indication for hospitalization, recorded after June 1, 2020 (available for 54% of sample) found that hospitalizations in the first and second trimester were more likely due to COVID-19-related illness, while hospitalizations in the third trimester were more likely due to delivery and other obstetric needs. Slightly more than half (54.5%, n=326) did not have COVID-19 symptoms on admission. Among the 272 women with symptoms — most frequently fever and chills or cough — 16.2% required intensive care unit admission, 8.5% required mechanical ventilation, and 0.7% (2 women) died. Among hospitalizations that included pregnancy completion (458 of 598 hospitalizations), 10 (2.2%) resulted in pregnancy loss (5% of symptomatic women and 0.9% of asymptomatic women). Overall, 12.6% of live births were pre-term (23% among symptomatic and 8% among asymptomatic women).

Study Strengths

The key strength of this study is the population-based sampling frame, that while not designed to be representative of pregnant women specifically, nevertheless includes a racially/ethnically diverse sample of hospitalized pregnant women with COVID-19 from 13 US states. The data were abstracted by trained surveillance officers using systematic protocols, and the data was fairly complete with respect to race/ethnicity, comorbidities, and pregnancy outcomes during the hospitalization.

Limitations

Data from more than two-thirds of the hospitalized cases among women of reproductive age were not abstracted, and it is unclear how the included convenience sample may differ from the remainder of the records. Comparisons between the symptomatic and asymptomatic groups were unadjusted for key risk factors. Data on maternal and neonatal mortality were not collected beyond the initial hospitalization period, potentially undercounting deaths. The surveillance system does not enable the comparison of outcomes to those of pregnant women who were admitted to the same hospitals at the same time, but were not infected with SARS-CoV-2. Finally, this study does not provide information on birth outcomes among women who recovered from COVID-19 earlier in their pregnancies.

Value added

This study reported higher levels of preterm birth and pregnancy loss among women infected with SARS-CoV-2 with symptoms as compared to women who are asymptomatic, among a more representative sample than prior data from the US.