Welcome to the McGraw-Hill COVID-19 channel. This week we have information about the sensitivity of SARS-CoV-2 testing and how it relates to the new variants of SARS-CoV-2. We also have information from Pfizer/BioNTech about the effectiveness of the current vaccine against the “British” variant, strain B 1.1.7 (AKA 20B/501Y.V1, VOC 202012/01). Finally, there is a new study about the long-term consequences of COVID-19 and a new negative study of tocilizumab in those not requiring mechanical ventilation.
The FDA is warning about false negative tests in those infected with SARS-CoV-2 variants. As the genetic makeup of the SARS-CoV-2 varies, so does the sensitivity of testing. The FDA notes a reduced sensitivity of the following tests for the British variant, B 1.1.7 (AKA 20B/501Y.V1, VOC 202012/01):
- TaqPath COVID-19 Combo Kit,
- Linea COVID-19 Assay Kit.
Since these lab tests target multiple sites, the overall sensitivity of the tests has not changed. A third test, the Accula SARS-Cov-2 Test, is undergoing further testing. The FDA recommends the following (verbatim):
- Be aware that genetic variants of SARS-CoV-2 arise regularly, and false negative test results can occur.
- Be aware that tests that use multiple genetic targets to determine a final result are less likely to be impacted by increased prevalence of genetic variants.
- Consider negative results in combination with clinical observations, patient history, and epidemiological information.
- Consider repeat testing with a different test (with different genetic targets) if COVID-19 is still suspected after receiving a negative test result.
There are also specific recommendations for lab staff including an increase in whole genome testing. The complete recommendations can be found here.
The Pfizer/BioNTech vaccine is effective against the British (B 1.1.7) SARS-CoV-2 variant in the lab. This is a prepublication study of the effect of vaccine-induced neutralizing antibodies on the newly described UK variant. They exposed lab generated isotype viruses to the sera of 20 patients who had been previously immunized with the Pfizer/BioNTech vaccine. The outcome was the antibody level required for 50% reduction in infectivity (plaque reduction). There was no difference between the antibody level required for a 50% neutralization of the B 1.1.7 variant versus the unmutated virus (BNT162b2).
The authors point out that there are additional mutations in wild-type virus that they did not account for; they looked only at the one mutation in isolation. The full study can be found here. We are still waiting for the data from Moderna about their vaccine.
- Xie X et al. Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera bioRxiv 01.07.425740; doi: https://doi.org/10.1101/2021.01.07.425740
Many hospitalized patients with moderate to severe COVID-19 have residual symptoms 6 months after discharge. This is a study of 2469 patients who were hospitalized for COVID-19; participants were a mean of 186 days post-discharge. Patients were asked about continued symptoms and were stratified according to their inpatient 7-point COVID-19 severity scale.
Overall, 63% percent reported fatigue or muscle weakness while 26% reported difficulty sleeping and 23% reported anxiety. Of those who had a severity scale of 5-6 29% had an impaired 6-minute walking distance. Fifty-six percent of those with a severity score of 5-6 had lung diffusion impairment while 29% if those with a severity score of 4 had diffusion impairment. A CrCl of less than 90 mL/min per 1·73 was found in 35%.
This likely underestimates the problem since 30% of patients were excluded (736 of 2469). Exclusion criteria included the inability to “move freely” (including from osteoarthritis, stroke or pulmonary embolism), those living in a nursing facility and those who had been readmitted. It also doesn’t tell us about sequelae in those who were not hospitalized. Nor is there a control group of those hospitalized with other illnesses. None-the-less it gives us concrete information about problems that may need to be addressed post-hospitalization. The full study can be found here.
- Huang C. et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. The Lancet January 8, 2021 :https://doi.org/10.1016/S0140-6736(20)32656-8
Another negative study of tocilizumab in those with COVID-19 pneumonia not requiring invasive ventilation. This is a study of 389 patients with COVID-19 pneumonia randomized 2:1 to treatment with tocilizumab versus placebo. All patients were PCR positive and had oxygen saturations of <94% but were excluded if they required CPAP, BiPAP or invasive ventilation. The outcome was death or need for invasive ventilation at day 28. The primary outcome (death + need for invasive ventilation) favored treatment with tocilizumab. However, there was no difference in the rate of death or the median time to clinical improvement. In fact, there was a trend toward worse outcomes in the tocilizumab group (10.4% in the treatment group vs 8.6% in the placebo group). The full study can be found here.
This doesn’t really push us to change the current Infectious Disease Society of America (IDSA) recommendation that tocilizumab not be used routinely in COVID-19.
Salama C et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia N Engl J Med 2021; 384:20-30 DOI: 10.1056/NEJMoa2030340