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July 2 | FINAL Weekly COVID-19 LST Report

Epidemiology

· SARS-CoV-2 B.1.1.7 REINFECTION AFTER PREVIOUS COVID-19 IN TWO IMMUNOCOMPETENT ITALIAN PATIENTS: A double case report from the ASST Sette Laghi by microbiology researchers found, when analyzing one 56-year old patient in December 2020 with confirmed B.1.1.7. strain infection and interstitial pneumonia, the amino acid substitutions N501Y and A570D were confirmed. In another case of a 58-year old male in January 2021, with the same strain and detectable mutation, diagnosis of interstitial pneumonia necessitated treatment in the subacute medical unit. These reports provide a possible clinical profile for reinfection with the B.1.1.7 strain, and authors suggest that more cases of reinfection with B.1.1.7 are likely undetected.

Understanding the Pathology

· Nasal ciliated cells are primary targets for SARS-CoV-2 replication in early stage of COVID-19: Investigators at the Institute for Basic Science in South Korea analyzed nasal epithelial samples from humans and nonhuman primates infected with SARS-CoV-2. By combining immunofluorescence staining and single cell RNA-sequencing, they found high levels of viral proteins in the setting of low levels of mRNA with proteins generally localized to the apical side of multiciliated cells (Figure 2, B-G) suggesting that mRNA levels poorly correlate to cellular localization. Additionally, they found that SARS-CoV-2 replication was localized to these nasal multiciliated cells when compared to oral squamous cells (Figure 4, B and C). While the findings suggest early replication in shedding epithelia of the nasal cavity, the lack of inclusion of glandular epithelial cells warrants study of these cells as potential points of replication for the virus. Transmission & Prevention

· Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial: An international team of researchers conducted a phase 3 randomized clinical trial on the efficacy and safety of the WIVO4 and HBO2 inactivated SARS-CoV-2 vaccines in 40,382 symptomatic COVID-19 adults. Primary efficacy end point was determined to be 72.8% ([95% CI 58.1%-84.2%]; P less than 0.001) for WIVO4 and 78.1% ([95% CI 64.8%-86.3%]; P less than 0.001) for HBO2 (Table 2, Figure 2). 100% efficacy was seen against severe COVID-19. 44.2% of participants in the WIVO4 group reported adverse reactions, 41.7% in the HBO2 group, and 46.5% in the alum-only group (Figure 3). These findings suggest the significant efficacy and safety of these two vaccines against SARS-CoV-2 infection while also demonstrating their ability to prevent further transmission. · Persistence of Antibody and Cellular Immune Responses in COVID-19 patients over Nine Months after Infection: A cross-sectional study conducted at the Beijing Institute of Microbiology and Epidemiology assessed blood samples taken from 59 patients who recovered from COVID-19 between 257 and 343 days post-SARS-CoV-2 infection. They found at the designated time point 90% of patients possessed detectable IgG antibodies against the virus spike and nucleocapsid proteins, 60% possessed antibodies against the receptor binding domain (Figure 1), and 70% possessed specific memory B and T cell responses (Figure 2). The findings suggest that immunity against the virus largely persists at about one year after infection, though the small sample size warrants future large-scale studies.

· Quantifying the risk of SARS-CoV-2 reinfection over time: Researchers at the Health Information and Quality Authority in Ireland. performed a systematic review of of 11 cohort studies including 615,777 patients who recovered from COVID-19 to quantify risk of reinfection with SARS-Cov-2. The median follow-up was 131 days (4.4 months; range of medians: 54–210 days) and with a maximum follow-up of 10 months. They found reinfection rates to be between 0-1% (median PCR-confirmed reinfection rate: 0.27%) with no studies reporting an increase risk of infection with increasing time since recovery. · Characteristics of COVID-19 Cases and Outbreaks at Child Care Facilities - District of Columbia, July-December 2020: In a Morbidity and Mortality Weekly Report from the CDC, researchers discuss their observational study of COVID-19 cases and outbreaks at 469 child care facilities in the District of Colombia from July-December 2020. A total of 319 cases were identified from 112 facilities, 180 of whom were teachers or staff members. 27 facilities had 29 index cases that caused an additional 127 cases, which qualify as an outbreak. These results suggest that outbreaks at child care facilities were relatively low and implementing preventative measures can further decrease transmission.

· Indoor Air Changes and Potential Implications for SARS-CoV-2 Transmission: A review article conducted by researchers affiliated with Harvard University, University of Michigan, and HOK Architects in Chicago, Illinois provide rational for increasing the current ventilation and filtration standards for indoor spaces levels closer to hospital standards (eTable), since SARS-CoV-2 outbreaks have been largely associated with time spent indoors and low-level ventilation. Higher ventilation and filtration rates allow for rapid removal of particles from indoor air to lessen the duration of respiratory aerosols and far-field transmission (within same room by beyond 6 feet) among room occupants. Considerations for implementing these strategies include cost, minimal impact on close-contact transmission, use in spaces where masks are not worn all the time, and scale of ventilation/filtration to the amount of occupants in the rooms. Improved ventilation and filtration strategies should be a continued emphasis in buildings even after the pandemic as a holistic risk reduction strategy.

R&D: Diagnosis & Treatments

· Dynamics of anti-SARS-CoV-2 IgG antibodies post-COVID-19 in a Brazilian Amazon population: An observational cohort study conducted at the Federal University of Pará in Brazil followed 125 anti-SARS-CoV-2 antibody positive volunteers for 90 days following COVID-19 diagnosis to assess the persistence of antibodies. They found that persistence was detected after 90 days in 87 participants (69.6%) (Table 3) with symptoms lasting longer in those with persistent IgG response (greater than or equal to 21 days, compared to less than or equal to 7 days) (Table 2). The findings suggest a potentially high rate of immunity loss in this population. · Bamlanivimab for Prevention of COVID-19: An editorial article written by a researcher affiliated with Harvard Medical School discusses a randomized, double-blind, placebo-controlled trial in 74 skilled nursing and assisted living facilities with 966 total participants to evaluate single IV 4200 mg dose of Bamlanivimab (a SARS-CoV-2 neutralizing monoclonal antibody) in COVID-19 prophylaxis. They found a significant reduction in incidence of symptomatic COVID-19 compared with placebo (8.5% vs. 15.2%, OR 0.43, 95% CI 0.28-0.68) as well as moderate to severe COVID-19 by day 57 (8.3% vs. 14.1%, OR 0.46, 95% CI 0.29-0.73). They additionally found significant decreases in viral loads in the Bamlanivimab group compared with placebo (2.44 vs. 3.64) and no COVID-19 related deaths among those in the treatment groups versus 5 deaths in the control. These findings suggest that passive immune prophylaxis with Bamlanivimab could abort outbreaks and reduce transmission in similar residential facilities.


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