COVID-19 Literature Situation Report July 27, 2020

• Wellinghausen et al. conducted a retrospective analysis of serum samples (n=158) from a German cohort of PCR confirmed COVID-19 outpatients and asymptomatic contact persons (n=158) and found that overall positivity rate for SARS-CoV-2-IgG was 81% among outpatients and 15% among asymptomatic contacts. 
• Symptomatic outpatients had a higher viral load, based on PCR cycle counts, compared to asymptomatic contacts (5-7 threshold cycles). Viral load was also positively correlated with SARS-CoV-2-IgG ratio. The authors hypothesize that the lower viral load in asymptomatic cases could explain the lower sero-prevalence in those without symptoms. 

Wellinghausen et al. (July 6, 2020). SARS-CoV-2-IgG Response Is Different in COVID-19 Outpatients and Asymptomatic Contact Persons. Journal of Clinical Virology. https://doi.org/10.1016/j.jcv.2020.104542  

• Based on a retrospective cohort study of COVID-19 patients in Hubei, China (n=446), early administration of interferon-a2b was associated with lower likelihood of in-hospital mortality versus no interferon (OR=0.05, 95% CI: 0.01-0.37), while late interferon therapy was associated with greater likelihood of mortality (OR=6.82, 95% CI: 1.14-40.8). This may indicate that the timing for interferon therapy may be important. Most of the patients in the study who received interferon also received the antiviral agents umifenovir or lopinavir boosted with ritonavir. 

Wang et al. (July 18, 2020). Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2020.07.005  

• A multicenter cohort study based in the UK found that lateral flow point-of-care and ELISA tests for SARS-CoV-2 antibodies had good positive and negative predictive values when conducted among a carefully selected population with suspected SARS-CoV-2 infection. The authors conclude that these test have potential for late case identification among healthcare workers with mild to moderate SARS-CoV-2 infection, but also discuss important limitations, including late development of bands on lateral flow assays that may limit their application. 

Pallett et al. (July 24, 2020). Point-of-Care Serological Assays for Delayed SARS-CoV-2 Case Identification among Health-Care Workers in the UK: A Prospective Multicentre Cohort Study. The Lancet Respiratory Medicine. https://doi.org/10.1016/S2213-2600(20)30315-5  

• [Pre-print, not peer reviewed] Based on PCR testing for SARS-CoV-2 among nursing home residents (n=16,966) and staff (n=15,514) with or without symptoms in Massachusetts (April 9 to June 9), 13% of residents and 4% of staff tested positive. Of those without symptoms, 13% of residents and 4% of staff tested positive, compared to 53% of residents and 18% of staff with symptoms. There was a statistical, though not meaningful, difference in viral loads between patients with and without symptoms (mean difference=0.71 cycles, p=0.006). 

Lennon et al. (July 26, 2020). Comparison of Viral Levels in Individuals with or without Symptoms at Time of COVID-19 Testing among 32480 Residents and Staff of Nursing Homes and Assisted Living Facilities in Massachusetts. Pre-print downloaded July 27 from https://doi.org/10.1101/2020.07.20.20157792 

• A randomized trial of hydroxychloroquine, alone or with azithromycin, for treatment of mild- to moderate COVID-19 found no effect on improving clinical status at 15 days after hospital admission. Cavalcanti et al. conducted a multicenter, randomized, open-label, three-arm controlled trial (n=504) in Brazil and found that the odds of having a higher score (worse clinical status) on a 7-point ordinal scale at 15 days was not affected by hydroxychloroquine alone (OR=1.21, 95% CI 0.69-2.11), or hydroxychloroquine and azithromycin (OR=0.99, 95% CI 0.57-1.73), compared to standard care. 

Cavalcanti et al. (July 23, 2020). Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2019014 

• [Pre-print, not peer reviewed] Using PCR test results from a national reference laboratory (n=277,601), Greene et al. compared the age distribution of positive SARS-CoV-2 test results between March-April and June-July and found that the median age of people testing positive has declined over time from 41 years (IQR 29.0-54.1) to 36 years (IQR 24.0-50.2).  
• A sub-analysis showed that this trend was only observed for outpatient populations, while the minority of positive tests coming from inpatients (2%) showed an increase in age over time. Additionally, the test positivity rate increased among patients under 50 years old and decreased among patients over 50 years. 

Greene et al. (July 24, 2020). Decreasing Median Age of COVID-19 Cases in the United States Changing Epidemiology or Changing Surveillance. Pre-print downloaded July 27 from https://doi.org/10.1101/2020.07.22.20160119 

• A prospective multicenter study of pediatric patients in France (n=438) showed that a symptom-based SARS-CoV-2 testing strategy failed to identify 45% (95% CI 24%-68%) of hospitalized SARS-CoV-2 infected children at the time of hospital admission. 

Poline et al. (July 25, 2020). Systematic SARS-CoV-2 Screening at Hospital Admission in Children: A French Prospective Multicenter Study. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa1044  

• A survey of a national sample of US parents with at least 1 child younger than 18 (n=1,011) found that 27% of parents reported worsening mental health for themselves, 14% reported worsening behavioral health for their children, and nearly 1 in 10 experienced both. A decrease in food security, employer-sponsored insurance, and regular childcare were also reported. 

Patrick et al. (July 24, 2020). Well-Being of Parents and Children During the COVID-19 Pandemic: A National Survey. Pediatrics. https://doi.org/10.1542/peds.2020-016824  

• Halford et al. analyzed Google Trends data (March-April) representing searches in the US for terms related to suicide and known suicide risk factors and found that, while the proportion of suicide-related queries was lower than expected, queries representative of financial difficulty, help-seeking, and general mental health concerns were elevated, suggesting that the COVID-19 pandemic may have caused an increase in suicide risk factors. 

Halford et al. (July 24, 2020). Google Searches for Suicide and Suicide Risk Factors in the Early Stages of the COVID-19 Pandemic. PLOS ONE. https://doi.org/10.1371/journal.pone.0236777 

• Using an age-structured agent-based model parametrized with demographics from Ontario, Canada, Abdollahi et al. found that increasing the duration of school closures from 3 to 16 weeks reduced the COVID-19 attack rate by 7%-13% when contacts among school children were restricted by 60-80%. Adding varying degrees of voluntary social isolation among mildly symptomatic persons further reduced the attack rate. 

Abdollahi et al. (July 24, 2020). Simulating the Effect of School Closure during COVID-19 Outbreaks in Ontario, Canada. BMC Medicine. https://doi.org/10.1186/s12916-020-01705-8  

• Seigler et al. observed that participants surveyed using social media (n=1,435) were most willing to test for SARS-CoV-2 infection with a home saliva specimen (92%), followed by home swab (88%), drive-through swab (71%), and clinic-collected swab (60%). Additionally, 68% of participants indicated they would be more likely to get tested if there was a home testing option. 

Siegler et al. (June 30, 2020). Willingness to Seek Diagnostic Testing for SARS-CoV-2 With Home, Drive-through, and Clinic-Based Specimen Collection Locations. Open Forum Infectious Diseases. https://doi.org/10.1093/ofid/ofaa269  

• Rodriguez-Diaz et al. compared counties with a greater proportion of Latino residents than the US average (n=443) and all other counties (n=2700) and found that COVID-19 cases were greater in Northeastern and Midwestern Latino counties (RR=1.42 and RR=1.70, respectively), while deaths were greater in Midwestern Latino counties (RR, 1.17, 95% CI 1.04-1.34). 
• Factors such as greater monolingual Spanish speakers, employment rates, and less social distancing were associated with higher diagnostic rates, suggesting that structural factors may cause differences in risk among Latino populations. 

Rodriguez-Diaz et al. (July 23, 2020). Risk for COVID-19 Infection and Death among Latinos in the United States: Examining Heterogeneity in Transmission Dynamics. Annals of Epidemiology. https://doi.org/10.1016/j.annepidem.2020.07.007