COVID-19 Literature Situation Report May 12, 2021

• SARS-CoV-2 index cases with lower PCR cycle threshold (Ct) values (suggesting a higher viral load) tended to have a higher proportion of contacts infected with SARS-CoV2, according to a study combining testing and contact tracing data from England between September 2020 and February 2021. Attack rates were 12% for index cases with Ct=15 and 5% for index cases with Ct=30. Attack rates were 55% higher among index cases with infections with S gene target failure (a known proxy for the B.1.1.7 variant). Attack rates were highest among household contacts (9%) followed by household visitors (7%), and lower among outdoor contacts (3%) and work/education contacts (5%). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/educational settings.

Lee et al. (May 11, 2021). SARS-CoV-2 Infectivity by Viral Load, S Gene Variants and Demographic Factors and the Utility of Lateral Flow Devices to Prevent Transmission. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab421

• [Pre-print, not peer-reviewed] The proportion of people with SARS-CoV-2 positive PCR tests was higher among participants living in houses with more occupants than rooms (“overcrowded houses”) when compared to houses with fewer occupants (7% vs 3%) per room, according to a household community cohort study in England and Wales (n=10,33) conducted between June 2020 to May 2021. Adjusting for age, sex, ethnicity, household income, and geographical region, the likelihood of having a positive PCR SARS-CoV-2 antigen test was nearly 4-fold higher among those living in houses with more occupants than rooms. Similarly, the likelihood of being positive for anti-SARS-CoV-2 antibodies was nearly 3-fold higher among those in overcrowded houses.

Aldridge et al. (May 11, 2021). Household Overcrowding and Risk of SARS-CoV-2 Analysis of the Virus Watch Prospective Community Cohort Study in England and Wales. Pre-print downloaded May 12 from https://doi.org/10.1101/2021.05.10.21256912

• A systematic review and meta-analysis of 5 randomized placebo-controlled trials (n=7,540 total participants) found no significant evidence that remdesivir (100 mg over 10 days) reduced all-cause mortality (RR=0.94, CI 0.82-1.07), clinical progression (RR=1.08, CI 0.99-1.18), or diarrhea (RR=0.82, CI 0.40-1.66). The authors conducted a trial sequential analysis and found that the meta-analysis was underpowered to detect a 10% reduction in all-cause mortality at 0% sample heterogeneity and 11% baseline risk (required n=24,281).

Okoli et al. (May 11, 2021). Remdesivir for Coronavirus Disease 2019 (COVID-19): A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials. Infectious Diseases. https://doi.org/10.1080/23744235.2021.1923799

• Participants with severe COVID-19 randomized to receive convalescent plasma (n=150) had significantly lower 28-day mortality (OR=0.44, 95% CI: 0.22-.91) compared to those receiving controlled plasma (n=73) in a randomized double-blind controlled trial conducted in New York and Brazil. However, no significant improvement in clinical status, as measured on an ordinal scale, was observed at 28 days (OR=1.50, 95% CI: 0.83-2.68) and the authors caution that the difference in mortality was not observed in larger inpatient trials explicitly designed to test for effects on mortality. The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160. No evidence of SARS-CoV-2 variants linked with neutralization escape was found in a subset of samples from Brazil.

O’Donnell et al. (May 11, 2021). A Randomized Double-Blind Controlled Trial of Convalescent Plasma in Adults with Severe COVID-19. Journal of Clinical Investigation. https://doi.org/10.1172/JCI150646

• 34% of COVID-19 patients in a multicenter cohort in Spain (n=13,932) were inappropriately prescribed antibiotics, defined as the patient not fulfilling any accepted criteria for use of antibiotics such as shock, sepsis, or coinfections. Patients admitted to the hospital early in the pandemic (February to March 2020) and presenting with dry cough, fever, and flu-like symptoms were more likely to be inappropriately prescribed antibiotics.

Calderón-Parra et al. (May 11, 2021). Inappropriate Antibiotic Use in the COVID-19 Era: Factors Associated with Inappropriate Prescribing and Secondary Complications. Analysis of the Registry SEMI-COVID. PLOS ONE. https://doi.org/10.1371/journal.pone.0251340

• [Pre-print, not peer-reviewed] In a cohort of US mothers testing positive for SARS-CoV-2 during pregnancy (n=145), anti-SARS-CoV-2 antibodies were detected in 65% and 58% of maternal and cord blood samples at delivery, respectively. The IgG transplacental transfer ratio was significantly higher among women receiving their first maternal positive PCR test 60-180 days before delivery compared to those receiving their first test <60 days before delivery (ratio 1.2 vs 0.6). Infants were followed with serial serologic analysis and 2 of 147 infants seroconverted (defined as high levels of IgG and IgM) by as early as 2 weeks, including one premature infant with confirmed intrapartum infection. IgG antibody levels in the infants correlated with IgG levels in the cord blood. In infants with maternally derived antibody, 8% (4 of 48) became undetectable at 1-4 weeks and 38% (5 of 14) were undetectable by 13-28 weeks, with some antibodies persisting up to 6 months of age. 

Song et al. (May 3, 2021). Passive and Active Immunity in Infants Born to Mothers with SARS-CoV-2 Infection during Pregnancy: Prospective Cohort Study. Pre-print downloaded May 12 from https://doi.org/10.1101/2021.05.01.21255871

• [Pre-print, not peer-reviewed] Sera of participants with detectable spike antibodies produced by natural infection had higher levels of anti-SARS-CoV-2 spike IgG antibodies against the wild-type strain and variants of concern (B.1.1.7, B.1351, and P.1) at least one week after a single dose of the Oxford-Astrazeneca vaccine (n=83) compared to sera from a mixed group of seronegative and seropositive participants at least 2 weeks after the second dose of the Pfizer-BioNTech vaccine (n=149; 36 with previous infection and 113 without). Similarly, levels of pseudo-neutralizing spike-ACE2 blocking antibodies against the wild-type strain and variants of concern were also higher among seropositive individuals with a single dose of the Oxford-Astrazeneca vaccine compared to a mixed group of seronegative and seropositive vaccine recipients after 2 doses of the Pfizer-BioNTech vaccine. [editorial note: Previous studies have clearly established that seropositive individuals receiving mRNA vaccines have much higher antibody titers after vaccination compared to seronegative individuals receiving the same vaccine. Since the authors of this preprint analyzed a combined group of seronegative and seropositive individuals receiving an mRNA vaccine, the editors advise caution in interpreting the data from this preprint].

Havervall et al. (May 11, 2021). Antibody Responses After a Single Dose of ChAdOx1 NCoV-19 Vaccine in Healthcare Workers Previously Infected with SARS-CoV-2. Pre-print downloaded May 12 from https://doi.org/10.1101/2021.05.08.21256866

• Anti-SARS-CoV-2 nucleocapsid (N) antibodies were detected in 7% of pets (14 of 198) in a serosurvey conducted in Italy from March to June 2020. All 14 seropositive animals lived with SARS-CoV-2-infected owners. In the households of SARS-CoV-2–infected owners, 20% (11 of 54) of cats and 3% (3 of 93) of dogs were seropositive. The proportion of seropositive pets increased with length of exposure, with all 14 cases classified as positive after ≥54 days of exposure. Clinical signs, such as cough and sneezing, were observed in 5 of 14 seropositive animals.

Colitti et al. (May 11, 2021). Cross-Sectional Serosurvey of Companion Animals Housed with SARS-CoV-2-Infected Owners, Italy. Emerging Infectious Diseases.  https://wwwnc.cdc.gov/eid/article/27/7/20-3314_article

• [Pre-print, not peer-reviewed] In a cohort of COVID-19 patients from the Netherlands (n=301) 82% of patients recovering from severe/critical disease reported at least one persistent symptom 12 weeks after illness onset, compared to 33% and 64% among those recovering from mild to moderate disease, respectively. At nine months after illness onset, 42% of participants continued to report at least one symptom. Recovery was approximately 50% slower among clinically obese patients (BMI ≥30) than those with BMI < 25.

Wynberg et al. (May 11, 2021). Evolution of COVID-19 Symptoms during the First 9 Months after Illness Onset. Pre-print downloaded May 12 from https://doi.org/10.1101/2021.05.05.21256710

• In the 30 days following a positive SARS-CoV-2 test, a decline in hospitalization (44% to 16%) and death (20% to 5%) was observed between February and July 2020 in a cohort of enrollees in the US Veterans Affairs healthcare system (n=55,952). Similar trends were also observed for 30-day incidence for ICU admission and mechanical ventilation. All trends subsequently plateaued through September 2020. The decrease in hospitalization persisted after adjustment for sociodemographic characteristics, comorbid conditions, documented symptoms and laboratory tests, including among subgroups of patients either hospitalized, admitted to the ICU or treated with mechanical ventilation. During the study period, there were also reductions in the use of hydroxychloroquine (57% to 0%) and azithromycin (48% to 17%) and increases in the use of dexamethasone (3% to 53%), corticosteroids (5% to 29%), and remdesevir (2% to 45%) among hospitalized patients.

Ioannou et al. (May 11, 2021). Trends over Time in the Risk of Adverse Outcomes among Patients with SARS-CoV-2 Infection. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab419

• [Pre-print, not peer-reviewed] Simulations of seating arrangements based on student enrollment data from the 2019-2020 academic year at the University of British Columbia found that assigned seating could reduce the mean number of contacts per student to 31 compared to 130 contacts per student with random seating. In combination with assigned seating, excluding large classes with >200 students further reduced the mean number of contacts per student to 20.

Daly-Grafstein et al. (May 11, 2021). Resuming In-Person Classes under COVID-19 Evaluating Assigned Seating Protocols in Limiting Contacts at Postsecondary Institutions. Pre-print downloaded May 12 from https://doi.org/10.1101/2021.05.07.21256844