COVID-19 Literature Situation Report June 1, 2021

• The anti-inflammatory drug colchicine did not change the rate of hospital admission or death related to COVID-19 (a composite endpoint) in a phase 3 double-blind placebo-controlled trial among non-hospitalized patients diagnosed with COVID-19 either by PCR testing or clinical criteria (OR=0.79, 95%CI: 0.61-1.03). The primary endpoint occurred in 4.7% (104 of 2,235) patients in the colchicine group and in 5.8% (131 of 2,253) of patients in the placebo group. Among those with PCR-confirmed COVID-19 (n=4,159), the primary endpoint occurred in 4.6% in the colchicine group vs 6.0% in the placebo group (OR=0.75, 95%CI: 0.57-0.99). Pneumonia occurred in fewer patients in the colchicine group (2.9% vs 4.1%), but diarrhea was reported in more patients in the colchicine group (13.7% vs 7.3%). Serious adverse events were similar in both groups.

Tardif et al. (May 2021). Colchicine for Community-Treated Patients with COVID-19 (COLCORONA): A Phase 3, Randomised, Double-Blinded, Adaptive, Placebo-Controlled, Multicentre Trial. The Lancet Respiratory Medicine. https://doi.org/10.1016/S2213-2600(21)00222-8

• Individuals with known prior SARS-CoV-2 infection had a 93% lower incidence of SARS-CoV-2 infection in the following year, according to a cohort study in Italy from February 2020 to February 2021. During a mean follow-up of 280 days, 5 reinfections occurred in 1,579 patients with a prior positive PCR test (mean interval between infections >230 days) compared to 528 new infections in 13,496 patients with negative PCR test results. Only 1 reinfection resulted in hospitalization. The authors note that the observation window ended before variants of concern began to spread in Italy.

Vitale et al. (May 28, 2021). Assessment of SARS-CoV-2 Reinfection 1 Year After Primary Infection in a Population in Lombardy, Italy. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2021.2959

• Following infection with SARS-CoV-2, the half-life of SARS-CoV-2 neutralizing antibodies was shorter than the half-life of antibodies directed against spike or nucleocapsid. In a cohort study of 148 individuals followed for a median of 8.3 months, antibodies followed a biphasic decay curve. Neutralizing antibody titers contracted the fastest, with an estimated half-life of 47 days in the first 0-6 months following infection and 27 days beyond 6 months post-infection. The half-life of anti-SARS-CoV-2 spike antibodies was estimated to be 97 days 0-6 months after symptom onset and 169 days 6 months or more after symptom onset. Anti-nucleocapsid antibodies declined faster than spike with half-life estimates of 47 and 168 days 0-6 months and 6 months or more after symptom onset, respectively. Older age (>50 years) and hospitalization were associated with higher antibody levels.

Terpos et al. (May 2021). SARS-CoV-2 Antibody Kinetics Eight Months from COVID-19 Onset: Persistence of Spike Antibodies but Loss of Neutralizing Antibodies in 24% of Convalescent Plasma Donors. European Journal of Internal Medicine. https://doi.org/10.1016/j.ejim.2021.05.010

• [Pre-print, not peer-reviewed] In a cohort of patients on intermittent hemodialysis (n=81), the Pfizer-BioNTech vaccine elicited diminished anti-SARS-CoV-2 antibody responses compared to healthy controls (n=34). Plasma and saliva IgG responses and antibody binding to variants of concern were lower in dialysis patients, particularly binding against the B.1.351 variant. Consistent with humoral responses, vaccine-induced cellular immune responses assessed by T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides were significantly diminished in dialysis patients.

Strengert et al. (May 29, 2021). Cellular and Humoral Immunogenicity of a SARS-CoV-2 MRNA Vaccine in Patients on Hemodialysis. Pre-print downloaded Jun 1 from https://doi.org/10.1101/2021.05.26.21257860

• [Pre-print, not peer-reviewed] Incidence of PCR-confirmed SARS-CoV-2 infection was 43% lower among unvaccinated spouses of healthcare workers (HCWs) vaccinated with mRNA vaccines (Pfizer-BioNTech and Moderna) 10 weeks after the first dose compared to spouses of unvaccinated HCWs, according to an analysis of national-level administrative data in Finland. The authors suggest that the vaccines may confer protection unvaccinated household members by reducing transmission from those who are vaccinated. Estimated direct vaccine effectiveness was 69% when comparing incidence of PCR-confirmed SARS-CoV-2 infection of vaccinated HCWs 10 weeks after the first dose with unvaccinated HCWs.

Salo et al. (May 29, 2021). The Indirect Effect of MRNA-Based Covid-19 Vaccination on Unvaccinated Household Members. Pre-print downloaded Jun 1 from https://doi.org/10.1101/2021.05.27.21257896

• Patient-facing information documents for COVID-19 vaccines hosted by regulatory bodies in the US (Food and Drug Administration) and in the United Kingdom (Medicines and Healthcare Products Regulatory Authority) were shown to have a readability score corresponding to a 7th to 8th grade level and an 8th to 9th grade level, respectively, according to the Flesch-Kincaid scale. 

Moore and Millar. (May 2021). Improving COVID-19 Vaccine-Related Health Literacy and Vaccine Uptake in Patients: Comparison on the Readability of Patient Information Leaflets of Approved COVID-19 Vaccines. Journal of Clinical Pharmacy and Therapeutics. https://doi.org/10.1111/jcpt.13453

• 97% (28 of 29) of healthcare workers with no prior infection had neutralizing activity against the SARS-CoV-2 B.1.351 variant of concern in their sera 1 week after receiving the second dose of the Pfizer-BioNTech vaccine, compared to only 60% (9 of 15) of healthcare workers who had COVID-19 6 months earlier. Geometric mean titers (GMTs) for neutralizing antibodies against B.1.351 in vaccinated individuals were 10-fold higher (33 vs 3.3) than in convalescent individuals. GMTs against the B.1.351 variant were reduced compared to the D614G and B.1.1.7 variants regardless of vaccination status, and GMTs in vaccinated individuals were higher than in convalescent individuals regardless of variant.

Marot et al. (May 29, 2021). Neutralization Heterogeneity of United Kingdom and South-African SARS-CoV-2 Variants in BNT162b2-Vaccinated or Convalescent COVID-19 Healthcare Workers. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab492

• [Pre-print, not peer-reviewed] Analysis of sera from individuals fully vaccinated with the Pfizer-BioNTech (n=30) and Moderna (n=19) vaccines ≥22 days after the second dose showed that neutralizing activity against pseudoviruses bearing mutated spike proteins from variants of concern was detectable in all participants but was reduced by 7-10 fold against the B.1.351 variant. Anti-SARS-CoV-2 IgG antibody levels correlated well with neutralizing titers for the wild-type strain as well as for variants of concern. 

Liu et al. (May 31, 2021). Correlation of Vaccine-Elicited Antibody Levels and Neutralizing Activities against SARS-CoV-2 and Its Variants. Pre-print downloaded Jun 1 from https://doi.org/10.1101/2021.05.31.445871

• An analysis of the immune response profile of COVID-19 patients suggests that T-cell exhaustion and impaired early antiviral response are characteristic of severe COVID-19 when compared to other causes of severe pneumonia. The authors enrolled participants with either or mild/moderate (n=86) or severe COVID-19 disease (n=35) and participants with other causes of hospital acquired pneumonia (n=25) and analyzed longitudinal samples of peripheral PBMCs using high-resolution flow cytometry. Additionally, the authors identified low circulating Natural Killer T-cell frequencies as a potential predictive biomarker for severe disease.

Kreutmair et al. (May 2021). Distinct Immunological Signatures Discriminate Severe COVID-19 from Non-SARS-CoV-2-Driven Critical Pneumonia. Immunity. https://doi.org/10.1016/j.immuni.2021.05.002

• Breakthrough infection rates were not statistically significantly different by sex or the type of mRNA vaccine administered, according to an analysis of data from a cohort of US veterans (n=14,875). Risk of breakthrough infection increased with age (HR=1.11) and presence of anemia (HR=1.37) and was lower among Black vs white veterans (HR=0.65). The 410 breakthrough SARS-CoV-2 infections were defined by a positive PCR test ≥7 days after receiving the second dose of an mRNA vaccine (Pfizer-BioNTech or Moderna) and corresponded to an incidence of 0.66 per 1,000 person-days. 

Butt et al. (May 2021). Rate and Risk Factors for Breakthrough SARS-CoV-2 Infection After Vaccination. Journal of Infection. https://doi.org/10.1016/j.jinf.2021.05.021

• Risk of SARS-CoV-2 infection in the UK between August 2020 and January 2021 was 80% lower among individuals with lab-confirmed infection but later testing antibody-negative (i.e. RNA-positive antibody-negative) compared to individuals who did not have infection (no test or RNA-negative and antibody-negative) during March to July 2020, according to an analysis of datasets obtained from 4 UK laboratories. Only 2 reinfections (>90 days after initial infection) occurred among 224 RNA-positive antibody-negative individuals (0.9%) compared to 2,054 second-wave infections in the 47,139 patients with no prior infection (4.4%). Risk of SARS-CoV-2 infection in RNA-positive antibody-negative individuals was similar to a subset of 2,087 patients who were RNA-positive and antibody-positive. As the study is based on laboratory datasets, the authors caution that testing may have been event-driven compared with datasets from routine screening.

Breathnach et al. (May 2021). Prior COVID-19 Protects against Reinfection, Even in the Absence of Detectable Antibodies. Journal of Infection. https://doi.org/10.1016/j.jinf.2021.05.024