2 Minute Medicine Rewind March 23, 2020

Clinical Course and Risk Factors for Mortality of Adult Inpatients With COVID-19 In Wuhan, China: A Retrospective Cohort Study

1. In-hospital COVID-19-related death was associated with older age, d-dimer levels greater than 1.0μg/mL, and higher Sequential Organ Failure Assessment upon assessment.

2. Median viral shedding in survivors was 20 days but was present until death in fatal cases.

3. Hypertension, diabetes, and coronary artery disease were the most common comorbidities in the sample of patients with laboratory-confirmed SARS-CoV-2 infection.

Evidence Rating Level: 2 (Good)

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Beyond clinical and epidemiological studies, few studies have tasked themselves with assessing risk factors, clinical course, or viral shedding. This retrospective cohort study included all adult inpatients (≥18 years) from two hospitals in Wuhan, China who had confirmed COVID-19 and either passed away or were discharged by January 31, 2020. With demographic, laboratory (serial samples for viral RNA detection), clinical, and treatment data from electronic medical records, researchers intended to compare survivors and non-survivors. A total of 191 patients were included in this study (median [IQR] age = 56.0 [46.0 to 67.0] years, 38% female), 71.7% of whom were discharged and the remainder passed away. Along with fever and cough, 40% of patients presented with lymphocytopenia. Roughly 95% were treated with antibiotics and 21% received antivirals. Statistically significant differences between survivors and non-survivors were found in terms of several treatments, with the non-survivors being more likely to receive these treatments: corticosteroids (p = 0.0005), intravenous immunoglobin (p<0.0001), high-flow nasal cannula oxygen therapy (p<0.0001), non-invasive mechanical ventilation (p<0.0001), invasive mechanical ventilation (p<0.0001), renal replacement therapy (p<0.0001), and extracorporeal membrane oxygenation (p = 0.0054). Approximately 48% of the sample possessed a comorbid conditionincluding hypertension (30%), diabetes (19%), coronary heart disease (8%). Analyses suggested increased odds of death associated with older age (OR 1.10, 95% CI 1.03 to 1.17 per year increase, p = 0.0043), d-dimer greater than 1μg/mL (OR 18.42, 95% CI 2.64 to 128.55, p = 0.0033), and higher Sequential Organ Failure Assessment score (OR 5.65, 95% CI 2.61 to 12.23, p<0.0001) at the time of admission. SARS-CoV-2 was detected until death in non-survivors but the median duration for viral shedding in survivors was 20.0 days (IQR 17.0 to 24.0). Regarding outcomes, the non-survivor group experienced sepsis (100%), respiratory failure (98%), acute respiratory distress syndrome (93%), heart failure (52%), septic shock (70%), coagulopathy (50%), acute cardiac injury (59%), acute kidney injury and secondary infection (50%), hypoproteinemia (37%), and acidosis (30%). Most common in survivors were sepsis (42%), respiratory failure (36%), and heart failure (12%), though all of these between-group comparisons were statistically significant. Overall, this study reported meaningful risk factors, clinical course, treatments undergone, and treatment outcomes in both COVID-19 survivors and non-survivors, serving as a meaningful contribution to the literature and frontline clinicians working with these patients.

Investigation of Three Clusters of COVID-19 In Singapore: Implications For Surveillance and Response Measures

1. Three clusters of COVID-19 were identified that resulted in further transmission beyond household clusters, including a cluster that did not recently travel to China, suggesting a need for strong surveillance strategies to minimize spread of the virus.

Evidence Rating Level: 3 (Average)

Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China following the detection of a cluster of viral pneumonia cases. Singapore confirmed its first case of COVID-19 on January 23, 2020, with the number rising to 89 people by February 22, 2020, the first 18 of whom having reported recent trips to Wuhan. As COVID-19 has become a serious pandemic, this study analyzed three clusters of COVID-19, to assess interactions and potential modes of transmission. Clinical and epidemiological data was utilized, including medical records, interviews and field investigations. The study found that the three clusters involved a Chinese tour group, company conference, and a church rather than simply household clusters. A total of 36 cases of individuals tested positive for COVID-19, relating to Clusters A (11), B (20), and C (5), denoting the setting of transmission, respectively. Cluster A included individuals with interrelated interactions with the tour group. The only overlap in activities among those in Cluster C was that five of the patients visited the church at the same time. Estimated median incubation period was four days (IQR 3 to 6). While there could be further tertiary causes of transmission within the households – non-primary cause – the authors report that the serial interval for the three household transmission pairs was likely 3 to 8 days. Clinically, the most common symptoms were fever (88%) and cough (82%). This study noted a six-month-old male who was asymptomatic until a fever spike two days into hospitalization. Median time from symptom onset to hospital admission was four days (IQR 3 to 9). For most cases, the course was uncomplicated and resolved in the first few days. However, admissions were protracted due to consistently positive findings of SARS-CoV-2 via nasopharyngeal swab testing. While no deaths were reported among these three clusters, close and prolonged exposure likely resulted in the COVID-19 cases, emphasizing the importance of hygiene in the prevention of transmission. While the first indication of human-to-human transmission was 11 days after the first case was noted, it is unlikely that temperature screening would have sufficiently detected concerns in travelers departing from Wuhan due to limited symptoms at the time. Therefore, this study and its authors suggest stronger surveillance to identify local cases even if they have not traveled to Wuhan or other international locations, as Cluster C is a prime example of individuals who presented with pneumonia but did not travel to China.

Association Between Proton Pump Inhibitor Use and Risk of Fracture in Children

1. The use of proton pump inhibitors (PPIs) in a pediatric cohort resulted in a small but statistically significant increase in fracture risk compared to children who were not using PPIs.

Evidence Rating Level: 2 (Good)

Proton pump inhibitors (PPIs) are the primary treatment for gastric acid-related disorders in children, despite this treatment being predominantly rooted in expert opinion rather than empirical data. Little is known related to their safety in pediatric populations yet have been prescribed at an increasing rate over recent years. This Sweden-wide register-based cohort study investigated the association between PPI use and fracture risk in a pediatric population – one known to be at risk for fractures. This study also engaged in a direct comparison of PPI and histamine-2 receptor antagonists (H₂RA). PPIs included omeprazole, esomeprazole, pantoprazole, rabeprazole, and lansoprazole. The target population was children under the age of 18 years during the study period of July 1, 2006 to December 31, 2016. Each child undergoing PPI treatment was matched with 30 non-PPI children. The final cohort was based on a 1:1 propensity score match and age groups of two-year bands. Children with organ transplant, cancer, congenital skeletal malformation, trauma-associated fracture in past 10 years, liver failure, and severe fractures were excluded. This resulted in a total of 115,933 child pairs with a mean (SD) follow-up period of 2.2 (1.6) years. During follow-up, more fractures were identified among the PPI group than the non-PPI group (difference 1.9 events per 1,000 person-years, HR 1.08, 95% CI 1.06 to 1.15). While no differences were found between groups for head or spine fractures, PPIs were associated with elevated risk of lower-limb fractures (HR 1.19, 95% CI 1.10 to 1.29), upper-limb fractures (HR 1.08, 95% CI 1.03 to 1.13), and other fractures (HR 1.51, 95% CI 1.16 to 1.97). When focusing on PPI use duration, the categories were ≤30 days (HR 1.08, 95% CI 1.03 to 1.13), 31 to 364 days (HR 1.14, 95% CI 1.09 to 1.20), and ≥365 days (HR 1.34, 95% CI 1.13 to 1.58). High-dimensional propensity score matching resulted in a consistent association (HR 1.10, 95% CI 1.06 to 1.15). Comparisons of PPI and H₂RA did not reach statistical significance (HR 1.06, 95% CI 0.97 to 1.15). While relatively small, this study suggests statistically significant differences in fracture risk between children who are exposed to PPI treatment compared to those who are not. This suggests that physicians must carefully weigh the costs and benefits when considering PPI treatment among pediatric populations.

Association of Family Member Detention or Deportation With Latino or Latina Adolescents’ Later Risks of Suicidal Ideation, Alcohol Use, and Externalizing Problems

1. Latino and Latina adolescents experiencing the detention and/or deportation of family members were found to have an increased risk of alcohol use, clinical externalizing behaviors, and suicidal ideation.

Evidence Rating Level: 2 (Good)

Since the expansion of 2017 policy changes in the US, the mental health effects on Latino and Latina youth who are experiencing deportation and/or detention have been a major concern. This prospective survey study conducted across suburban middle schools in Atlanta, Georgia randomly selected 547 Latino and Latina adolescents (mean age [SD] = 12.8 [1.0] years, 55.4% female) from sex and grade groups. A six-month follow-up was also conducted with these participants. Response rates varied between parents who were contacted (65.2%) and adolescents who were contacted with permission (81.5%). Approximately 24.9% of the sample had experienced the detainment or deportation of a family member within the past year. Controlling for baseline variables, these traumatic experiences were associated with a significant increase in odds of alcohol use (difference 11.1%, adjusted OR 2.98, 95% CI 1.26 to 7.04), clinical externalizing behaviors (difference 11.4%, adjusted OR 2.76, 95% CI 1.11 to 6.84), and suicidal ideation (difference 11.8%, adjusted OR 2.37, 95% CI 1.06 to 5.29). This study highlights the substantial psychological impacts of Latino and Latina adolescents who experience the deportation or detention of family members due to the US policies currently in place. These adolescents must be met with adequate primary care, with the inclusion of screening for mental health concerns to ensure that they can seek the appropriate treatment.

US Hospital Type and Proximity to Mass Shooting Events

1. Based on the 187 U.S. mass shooting events that occurred in 2019, non-trauma centers were more likely to be closer than trauma centers, which suggests a need for these facilities to be prepared for traumatic events in terms of both resources and staff.

Evidence Rating Level: 2 (Good)

Mass shootings have been rising in the past decade – a 300% increase over that period of time. Due to the ease with which large shooting events can overwhelm hospital resources, the placement and specialty areas of these hospitals is important. This retrospective study was concerned with the locations of Level 1 trauma centers (TCs) and non-trauma centers (NTCs) in relation to 2019 events because many patients are required to be transferred during these events, further risking their outcomes. Using the Gun Violence Archive for 2019 alone, 187 events occurred across 38 U.S. states, during which at least five or more injuries/deaths occurred by firearm. Case fatality rate was 23.8% (298 deaths) and 1,250 individuals were injured. At least one pediatric patient was involved in 54 of these events. NTCs were found to be closer to these shooting events (mean [SD] distance = 4.49 [4.34] miles) than both pediatric TCs (43.78 [82.90] miles) and adult TCs (13.14 [20.78]), all reaching significance at the 0.001 level. This study pointed out that the 23.8% mortality rate of these shootings exceeded that related to combat wounds (10%). The overall message is that it is more likely that an NTC will be the primary hospital for injured patients following these events. These facilities must be prepared for these types of events that formal TCs may otherwise be more equipped to handle due to sheer distance and expediency of care.

Image: PD

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