1st Advance: In 1796, Edward Jenner “found that an animal virus (cowpox) could protect against disease caused by a human virus (smallpox)… Jenner’s work ultimately led to the eradication of a disease that is estimated to have killed more than 300 million people in the 20th century”
2nd Advance: In 1885, Louis Pasteur developed an inactivated virus vaccine for rabies. This has led to the development of many other inactivated vaccines, including the influenza vaccine.
3rd Advance: In 1937, Max Theiler attenuated yellow fever virus by means of serial passage in mouse and chicken embryos. This has led to the development of numerous attenuated vaccines to prevent polio (Sabin, 1960s), measles (1963), mumps (1967), rubella (1969), varicella (1995), and rotavirus (2008).
4th Advance: In 1980, Stanford biochemists Richard Mulligan and Paul Berg developed recombinant DNA technology which led to vaccines containing purified surface proteins. This led to the hepatitis B virus (1986), human papillomavirus (2006), and influenza virus (2013) vaccines.
Some of the notable improvements related to vaccines:
In U.S., the incidence of polio dropped from 29,000 cases in 1955 to elimination
In U.S., during the “2019–2020 influenza season, the influenza vaccine prevented an estimated 7.52 million infections, 3.69 million medical visits, 105,000 hospitalizations, and 6300 deaths”
In U.S., the measles vaccine has nearly eliminated a virus that previously caused 2 million to 3 million infections, 50,000 hospitalizations, and 500 deaths every year
In U.S., “since the hepatitis B virus vaccine started being routinely recommended for newborns in the early 1990s, rates of hepatitis B virus infection among children younger than 10 years have fallen from about 18,000 per year to nearly zero”
Globally, “between 2000 and 2018, roughly 23 million measles deaths were prevented by vaccination…Live attenuated rotavirus vaccines are countering a virus that once killed more than 500,000 infants and young children each year”
5th Advance: In 2020 “with the recent authorization of mRNA vaccines, we have entered the fifth era of vaccinology. This class of vaccines doesn’t contain viral proteins; rather, these vaccines use mRNA, DNA, or viral vectors that provide instructions to cells on how to make such proteins. The SARS-CoV-2 pandemic will be an important test of whether these new platforms can fulfill their promise of creating safe, effective, and scalable vaccines more quickly than traditional methods.”
Among 9469 included participants, 1516 (16%) were regular users of acid suppressants, and 7953 (84%) were not…propensity score matching (PSM) was applied to match users of acid suppressants and nonusers.
Key findings:
The odds ratio (OR) of testing positive for COVID-19 associated with PPI or H2RA therapy in the PSM cohort was 1.083 (95% confidence interval [CI], 0.892–1.315) and 0.949 (95% CI, 0.650–1.387), respectively.
Omeprazole use alone was significantly related to an increased risk of SARS-CoV-2 infection from the subgroup analysis in patients with upper gastrointestinal diseases (OR, 1.353; 95% CI, 1.011–1.825)
My take: This study provides reassurance that acid blockers are unlikely to contribute to the risk of SARS-CoV-2 or to related complications.
“Due to their mechanism of action, both mRNA COVID-19 vaccines are recommended for all patients with CLD (compensated or decompensated) and immunosuppressed SOT recipients.”
“The AASLD recommends that providers advocate for prioritizing patients with compensated or decompensated cirrhosis or liver cancer, patients receiving immunosuppression such as SOT recipients, and living liver donors for COVID-19 vaccination based upon local health policies, protocols, and vaccine availability.”
JF Ludvigsson et al NEJM 2021; 384: 669-671. Full text: Open Schools, Covid-19, and Child and Teacher Morbidity in Sweden In this letter to the editor, the authors report on outcomes in Sweden, which kept schools open during the pandemic; time period: from March 1-June 30, 2020 (schools end around June 10th). Key findings:
Among 1-16 years of age (~1.95 million in total), 15 required ICU admission; there were no deaths in this age group
“Fewer than 10 pre-school teachers [1-6 years] and 20 schoolteachers received ICU care up to June 30, 2020.” Excluding health care workers, the occupational risk was similar to other occupations, with relative risk of 1.10 (0.49-2.49, 95% CI) and 0.43 (0.28-0.68, 95% CI) for preschool and school teachers respectively.
My take: This study suggests that school teachers are at similar risk for COVID-19 infection as other essential workers. In Sweden, during this timeframe, distancing but not masking was recommended. Thus, transmission rates could be lowered further.
Table 1 provides a summary of the recommendations and indicates a threshold for which routine pre-procedure testing may not be needed:
“For endoscopy centers where the prevalence of asymptomatic SARS-CoV-2 infection is low (<0.5%), the AGA suggests against implementing a pretesting strategy.”
Conditional recommendation, very low certainty evidence
Rationale: “In low-prevalence settings, a pretesting strategy may not be informative for triage due to the high number of false positives, thus PPE availability may drive decision-making.”
My take: Particularly after the rollout of vaccination to health care providers, routine testing for SARS-CoV-2 is not likely to be needed once the prevalence drops to low levels.
Key point: At 6 months after acute infection, COVID-19 survivors (n=1733 enrolled in study) were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations
NY Times (1/15/21): C.D.C. Warns the New Virus Variant Could Fuel Huge Spikes in Covid Cases “The new variant, called B.1.1.7, was first identified in Britain, where it rapidly became the primary source of infections, accounting for more than 80 percent of new cases diagnosed in London and at least a quarter of cases elsewhere in the country.”
Topical steroids were most effective in inducing histologic remission: 54.8% compared to 36.1% for PPIs and 18.5% for empiric elimination diet; histologic remission and response was 67.7%, 49.7%, and 48.1% respectively.
Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%).
However, PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%).
My take: This data (and others) indicate that topical steroids are most effective pharmacologic therapy; at some point, I expect that they will become the most frequently used.
“Layering two less specialized masks on top of each other can provide comparable protection [to N95]. Dr. Marr recommended wearing face-hugging cloth masks over surgical masks, which tend to be made with more filter-friendly materials but fit more loosely. An alternative is to wear a cloth mask with a pocket that can be stuffed with filter material, like the kind found in vacuum bags.”
45% had mild (ALT <2 x ULN), 21% moderate (ALT 2-5 x ULN), and 6.4% severe liver injury (SLI) (ALT >5 x ULN).
Patients with SLI had a more severe clinical course, including higher rates of intensive care unit admission (69%), intubation (65%), renal replacement therapy (RRT; 33%), and mortality (42%).
In multivariable analysis, peak ALT was significantly associated with death or discharge to hospice (OR, 1.14; P = 0.044), controlling for age, body mass index, diabetes, hypertension, intubation, and RRT
Going into this new year, the more concerning effects of COVID-19 pandemic for the liver is likely to be the increase is severe chronic liver disease related to alcohol (and perhaps fatty liver disease too). The second article (BL Da et al. Hepatology 2020; 72: 1102-1108. Coronavirus Disease 2019 Hangover: A Rising Tide of Alcohol Use Disorder and Alcohol‐Associated Liver Disease) discusses the expectation of increased liver disease due to alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Key points:
In China, reports indicate a “>2-fold increase in harmful drinking after COVID-19, an effect likely repeated in the United States where an estimated 12.7% of the population has AUD and ALD is responsible for the highest hospitalization cost burden among all chronic liver diseases (CLDs).”
Increased alcohol use is likely to worsen other chronic liver diseases in addition to ALD
In addition, all of these effects are compounded by avoidance of health care facilities and delays in care
My take: COVID-19 infections have direct effects on the liver. However, the increased use of alcohol as well as weight gain are likely to be more important in terms of liver-related morbidity and mortality.