Pandemic of panic

Vaccines

To what degree do vaccines prevent infection with SARS-CoV2 (Severe acute respiratory syndrome coronavirus 2)?

To what degree do vaccines prevent transmission of SARS-CoV2?

1. Chau et al. (8/10/21). Transmission of SARS-CoV-2 Delta Variant Among Vaccinated Healthcare Workers, Vietnam. Preprint. tracked breakthrough cases (for the Oxford-AstraZeneca COVID-19 vaccine) among healthcare workers in Ho Chi Minh City, Vietnam between 11-25 June 2021. Obtained genome sequences showed that the workers had been infected by a Delta variant virus with a distinct sequence when compared to those found in community transmission. The paper suggests this is due to transmission between vaccinated healthcare workers. No correlation was found between antibody levels and peak viral loads; the paper suggests this means the vaccine may not lower infectivity of breakthrough cases. They noted that "viral loads of breakthrough Delta variant infection cases were 251 times higher than those of cases infected with old strains detected between March-April 2020"; however, some have noted that this discrepancy could be due to testing at different stages of an infection.

To what degree do vaccines prevent severe outcomes from COVID-19 (coronavirus disease 2019)

Falling efficacy

Efficacy of "booster shots"

Vaccine adverse effects

1. Barda et al. Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections. reports a strong association between vaccination with the BNT162b2 (Pfizer-BioNTech) vaccine and myocarditis (risk ratio, 3.24; 95% CI, 1.55-12.44), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05-2.78), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01); herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73). It reported a mild association between vaccination and Bell's palsy (risk ratio, 1.32; 95% CI, 0.92 to 1.86). Vaccination showed protective effects against acute kidney injury and intracranial hemorrhage. The study also performed a comparison between individuals infected and uninfected with SARS-CoV2, finding a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12) as well as other adverse events in infected individuals, such as anemia and intracranial hemorrhage.

Note the inclusion of "persons who had had recent contact with the health care system" in the SARS-CoV2 infection group. A confounding factor here could be that a person who has worse health is more likely to need to interact with the health care system and therefore more likely to test positive on a PCR test. The study seems to suggest this, stating: "the spike in the incidence of certain adverse events in the first day of follow-up could indicate the initial clinical manifestation of the infection, but it could also be related to active testing for SARS-CoV2". In addition to the authors' warnings about comparison of the groups ("The effects of vaccination and of SARS-CoV-2 infection were estimated with different cohorts. Thus, they should be treated as separate sets of results rather than directly compared."), this study does not provide much useful information on individual risks, given particular risk factors, for either the vaccines or infection with the virus. Age stratification, for example, would be useful to determine whether the interaction between vaccination/SARS-CoV2 infection and side effects depends upon age.

Reliability of VAERS (Vaccine adverse events reporting system) data

Pfizer trial

Antibody dependent enhancement/Marek's effect

Data

Reliability of the PCR test

Reliability of hospitalization data

1. Fillmore et al. (9/13/21). The COVID-19 Hospitalization Metric in the Pre- and Post-vaccination Eras as a Measure of Pandemic Severity: A Retrospective, Nationwide Cohort Study. Preprint. attempts to line up "hospitalization plus a positive SARS-CoV-2 test" with disease severity to determine the appropriateness of the commonly-used hospitalization metric. This report studied all VA patients admitted to a VA hospital with a SARS-CoV-2 infection from March 1, 2020 to June 30, 2021. Among 47,742 admissions, 28,731 admissions had moderate-to-severe disease using criteria detailed in the report. Prior to 1/21/2021, when the first patient studied was fully vaccinated, 64.0% of hospitalized patients had moderate-to-severe disease. After 1/21/2021, 55.0% unvaccinated inpatients had a measurement of oxygen saturation (SpO2) less than 94% vs. 42.6% in vaccinated patients.

The report makes an important distinction in its background--that "patients hospitalized for the management of COVID-19 disease should be distinguished from patients who are hospitalized and incidentally found to be infected with SARS-CoV-2. Because data were taken from VA hospitals, the majority of patients (60.5%) were white; the median age among the cohort was 71.1; 94.5% were male. This is a very restrictive sample, so rates from this study should not be applied to the general population. Some commenters have noted that this study does not account for the emergence of different SARS-CoV-2 variants; however, the study does note that the delta variant did not appear to affect metrics: "proportions of patients with moderate-to-severe respiratory distress or being treated with dexamethasone did not appear to be rising at the end of the observation period (6/30/2021)". Additionally, I would note that both vaccinations and treatment methods for COVID-19 have evolved throughout the pandemic, which may affect the data presented here.

The effect of different testing policies for vaccinated/unvaccinated

SARS-CoV2/COVID-19

Means of transmission

Outdoor transmission

Risk factors for SARS-CoV2 infection/severity of COVID-19

1. Sandoval et al. (7/30/21). Risk factors for severity for COVID-19 in hospital patients age 18-29 years measures demographic and clinical risk factors for severe disease and 30-day readmission in Houston, Texas, USA from March 1 to December 7, 2020. It reports that increasing age, male gender, Hispanic ethnicity, obesity, asthma, congestive heart failure, cerebrovascular disease, and diabetes were predictive of severe disease diagnoses. Patients with class 2 or class 3 obesity had increased risk of composite disease outcomes compared to patients with a normal BMI (respectively, with an adjusted odds ratio [aOR] of 95% CI 1.9-5.1; 2.4-6.0). Non-Hispanic black race, obesity, asthma, myocardial infarction history, and household exposure were predictve of readmission.

2. Won Lee et al. (7/22/21). Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study measures associations between physical activity levels and SARS CoV-2 infection, severe illness from COVID-19, and COVID-19 related deaths on all Korean adults who were tested for SARS-CoV-2 between January 1, 2020 and May 15, 2020 (212,768). Adults who reported engaging in "sufficient" aerobic and muscle strengthening exercise had a significantly lower risk (aRR .85; 95% CI, 0.72-0.96) of SARS CoV-2 infection, severe COVID-19, or COVID-19 related death compared to "insufficiently active" adults (aRR .24; 95% CI, 0.05-0.99). Length of hospital stay was also shortened in patients who performed both aerobics and muscle strengthening. Effect sizes were high among the elderly, men, non-smokers, and those with a low Charlson comorbidity index.

Natural immunity

1. Gazit et al (8/25/21). Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections. Preprint. indicates that SARS-CoV-2-naive who had received the vaccine in Israel during January-February of 2021 had a 13x higher risk (95% CI, 8.08 to 21.11) of breakthrough infection compared to people with prior infection during the same period and a 27.02x risk (95% CI, 12.7 to 57.5) for symptomatic breakthrough infection compared to symptomatic reinfection. When allowing the time of infection to vary, SARS-CoV-2 naive vaccinees had a 6x higher risk (95% CI, 4.85 to 7.33) for breakthrough infections and a 7.13x (95% CI, 5.51 to 9.21) higher risk for symptomatic disease.

A few possible confounding factors have been noted. One--people who receive the vaccine may become more health-conscious and thus be tested more, increasing apparent positivity rates. I could make an argument in the other direction, though--that people who receive the vaccine may believe they can't get COVID and therefore don't have to be tested (or may engage in behaviors that cause them to become infected more often).

2. Israel et al (8/22/21). Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection. Preprint. studied antibody titer decay in the Israeli population using serology results between January 31, 2021 and July 31, 2021. It specifically tested for antibodies that attach to the SARS-CoV-2 spike protein. The study observed higher antibody titers in the first month following vaccination when compared to convalescent patients; however, antibody titers also decreased more rapidly (by up to 40% per month) in the vaccinated population compared to the convalescent population (~4% per month).

Re-infection with SARS-CoV2

Pre-existing immunity to SARS-CoV2 infection

Long COVID

Comorbidities, age, and risk

Risk from variants

1. Public Health England (9/3/21). SARS-CoV-2 variants of concern and variants under investigation in England. While previous versions of this report list the case fatality rate for different variants, it is no longer listed but is still calculable from the given numbers: while the Alpha/UK variant has a CFR of approximately 2.0%, the Delta variant has a CFR of approximately 0.3%. The report refers to a footnote under Table 3 to explain why CFRs are not comparable across variants, but the only footnote under Table 3 appears to be explaining "genotyped cases".

Some commenters have noted that CFRs may not be directly comparable due to variants affecting populations with different age compositions.

Animal reservoirs

Masks

Efficacy of mask mandates

1. Guerra, Damian & Guerra, Daniel (2021). Mask mandate and use efficacy for COVID-19 containment in US States studied mask mandates, compliance, and COVID-19 growth in the second and third US infection waves [June 1, 2020-March 1, 2021] and reported weak or no association between time of mask mandate and case growth rates in US states. Mask use was associated with lower growth rate minima but not growth rate maxima; the authors suggest this is because of the "tendency for faster case growth to occur at lower case prevalence" and further suggest that "mask use may be a lagging indicator of case growth".

2. Gettings, et al (5/21/21). Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools - Georgia, November 16-December 11, 2020 found that COVID-19 incidence was 37% lower in schools requiring teachers and staff members to wear masks and 39% lower in schools that improved ventilation. For ventilation, a combination of dilution and filtration methods showed the highest effectiveness at reduction of incidence (48% lower), compared to dilution methods (35% lower incidence; no statistical significance). Assessment of school characteristics was conducted by an online survey. Many COVID-19 cases were self-reported and no assessment of compliance was made. Notably, no statistically significant difference was found between schools that implemented hybrid instructional models, mask use among students, separation of desks or tables, usage of desk barriers, or the use of filtration ventilation methods only, vs. schools that did not implement these measures.

FOR https://www.healthaffairs.org/doi/10.1377/hlthaff.2020.00818

Studies on masks prior to COVID-19

1. Tunevall, Goran (5/1991). Postoperative wound infections and surgical face masks: A controlled study studied the effects of wearing face masks on postoperative wound infections, finding no statistically significant difference in wound infections after operations with or without face masks. It mentions a hypothesis that wearing a face mask may release skin scales carrying bacteria, causing wound infections. The study was conducted over the course of a two-year test period, randomizing whether operations would take place with or without masks on a weekly basis.

Filtration efficiency

Medical and psychological effects

Additional links

Association of American Physicians and Surgeons: Mask Facts

Drugs for prevention and treatment of COVID-19

Ivermectin

Remdesivir

1. Gerard et al (1/16/21). Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database.

Sotrovimab/Xevudy

N/A

Regeneron/Monoclonal antibodies

Lockdowns

Efficacy

Adverse effects

1. Williams et al (12/8/21). COVID-19 mortalities in England and Wales and the Peltzman offsetting effect. proposes a measure of excess deaths in England and Wales to include the impact of the first blanket lockdown rather than attributing all excess deaths to COVID-19. Uses modeling and finds that COVID-19 excess deaths make up 63% of the standard 5-year average excess deaths, and lockdown was, on net, associated with an extra 2,601 excess mortalities per week--indicating that any decrease in COVID-19 deaths was offset by unintended increase in mortality due to lockdown. The paper claims that a Peltzman offsetting effect is in play.

Common, but misleading or incorrect statements

99% of COVID hospitalizations/deaths are in the unvaccinated

Bell's palsy incidence in vaccinated same as in general population

Open questions

Do viruses only mutate within the unvaccinated?

Questionable

1. Karonova et al. (8/29/21). Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19 measured serum 25-hydroxyvitamin D [25(OH)D] levels in COVID-19 patients hospitalized from April to Decemberr 2020 at Botkin Clinical Infectious Hospital (St. Petersburg, Russia). Serum vitamin D levels were significantly lower in severe-course patients.