Useful COVID Studies

Coronavirus 2019 Infectious Disease Epidemic: Where We Are, What Can Be Done and Hope For – Jan, 2021

An excellent overview of the current state of the pandemic, covering our understanding of COVID-19 epidemiology, pathology, treatment, and vaccination.

Testing

Debiasing Covid-19 prevalence estimates

Debiasing Covid-19 prevalence estimates – hooick people are more cikely to get tested, especially when there is a wait time. People under 30 with symptoms are 1.5x more likely to test with no wait time, vs those without symptoms. Jumps to 2.9x with a 5-15min wait. 4.4x with a 15-30 min wait. This can impact population infection estimates.

Limited specificity of SARS-CoV-2 antigen-detecting rapid diagnostic tests at low temperatures – 2/6 tested rapid antigen tests showed cross-reactivity with other viruses at low temperatures (2-4˚C) (including an Abbott test). This can lead to high numbers of false positives from outdoor pop-up testing facilities.

Interpreting SARS-CoV-2 seroprevalence, deaths, and fatality rate — Making a case for standardized reporting to improve communication – Jan, 2021

An excellent discussion of CFR vs IFR, the accuracy of different testing methods, and an approach towards establishing standardized testing and reporting practices.

Clinical Performance of SARS-CoV-2 Molecular Tests – The clinical sensitivity of SARS-CoV-2 molecular assays was estimated between 58% and 96%, depending on the unknown number of false-negative results in single-tested patients

Good Articles

How the Oxford-AstraZeneca Vaccine Works

Transmission

Latest CDC Estimates of Disease Characteristics November, 2020 – Incubation period, doubling time, reproduction number (R0) etc.

Masks

Effectiveness of Mask Wearing to Control Community Spread of SARS-CoV-2 – Feb 10

Mask-wearing and control of SARS-CoV-2 transmission in the USA: a cross-sectional study 1/19/2021 — a 10% increase in self-reported mask-wearing was associated with an increased odds of transmission control (odds ratio 3·53, 95% CI 2·03–6·43

An evidence review of face masks against COVID-19 – Dec, 2020

An excellent review of the available evidence on masking, with a particular focus on the population-level impact vs. that for healthcare workers. Discusses issues like social stigma, supply chain, and sociological considerations.

Masks Do More Than Protect Others During COVID-19: Reducing the Inoculum of SARS-CoV-2 to Protect the Wearer

Masks and Acne or Other Dermatological Problems

Dermatological findings in patients admitting to dermatology clinic after using face masks during Covid-19 pandemia: A new health problem – 3/9/2021

We found that there were higher rates of itching, redness, rash, dryness and peeling and oly skin, acne formation after mask use. Exacerbating existing issues in 43.6% of acne patients, 100% of patients with acne rosacea, and 37.9% of patients with seborrheic dermatitis

In the study conducted by Zuo et al., it was found that skin symptoms, such as itching, redness, rash, burning, and swelling after mask use was 1.9 times more common in patients with a mask wearing time of more than 4 hours. Since these common symptoms are associated with friction, increase in the temperature, pressure and increased moisture, the probability of the symptoms also increases when these factors increase.

Veraldi et al. reported that the use of masks increased the severity of the disease during Covid-19 pandemia, as it was the cases in our study in patients with seborrheic dermatitis. They explained this by increased sebum secretion due to the use of masks and deterioration of the microbiota because of increased temperature and the use of masks caused malasezia spp. proliferation was explained by the deterioration of skin barrier permeability; and the increasing irritation also increased the disease severity with the sweating effect (23)

Increases sebum secretion leads to more acne.

Transmission Dynamics

Quantitative Microbial Risk Assessment for Airborne Transmission of SARS-CoV-2 via Breathing, Speaking, Singing, Coughing, and Sneezing – The expelled volume of aerosols was highest for a sneeze, followed by a cough, singing, speaking, and breathing. 

A systematic review of possible airborne transmission of the COVID-19 virus (SARS-CoV-2) in the indoor air environment – Feb, 2021

A review of existing evidence surrounding airborne transmission. 14 original research papers were included, with the conclusions that airborne transmission is a thing, and improved ventilation + air purification is necessary.

Size distribution of virus laden droplets from expiratory ejecta of infected subjects –  Analysis suggests that for viral loads < 2 × 105 RNA copies/mL, often corresponding to mild-to-moderate cases of COVID-19, droplets of diameter < 20 µm at the time of emission (equivalent to ~ 10 µm desiccated residue diameter) are unlikely to be of consequence in carrying infections

Particle sizes of infectious aerosols: implications for infection control – July 2020

Studies reviewed in this paper consistently show that humans produce infectious aerosols in a wide range of particle sizes, but pathogens predominate in small particles (<5 μm that are immediately respirable by exposed individuals.

Airborne Transmission of COVID-19: Aerosol Dispersion, Lung Deposition, and Virus-Receptor Interactions

Outdoor Transmission

Outdoor Transmission of SARS-CoV-2 and Other Respiratory Viruses: A Systematic Review – Five identified studies found a low proportion of reported global SARS-CoV-2 infections occurred outdoors (<10%) and the odds of indoor transmission was very high compared to outdoors (18.7 times; 95% confidence interval, 6.0–57.9).

Humidity

An Overview on the Role of Relative Humidity in Airborne Transmission of SARS-CoV-2 in Indoor Environments

At lower RH, due to rapid evaporation, solute concentrations increased but then became irrelevant after the droplets dried out, allowing virus viability to remain high. At the highest RH levels, the cumulative dose increased slowly and did not greatly impact virus viability, while at intermediate RH, cumulative dose was a crucial factor to reduce virus viability as the solute concentrations significantly increased while the droplet never completely evaporated.

Children & COVID

The role of children in the spread of COVID-19: Using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children – Feb 22, 2021

Children are 43% less likely to become sick and 63% less likely to spread it.

Asymptomatic Transmission

SARS-CoV-2 Transmission From People Without COVID-19 Symptoms – 59% of all transmission came from asymptomatic transmission, comprising 35% from presymptomatic individuals and 24% from individuals who never develop symptoms

A recent narrative review of 16 different studies estimated the rate of asymptomatic infection at 40–45% and they can transmit the virus to others for an extended period, perhaps longer than 14 days

  • Nearly 40% of children ages 6 to 13 tested positive for COVID-19, but were asymptomatic, according to just published research from the Duke University BRAVE Kids study. While the children had no symptoms of COVID-19, they had the same viral load of SARS-CoV-2 in their nasal areas, meaning that asymptomatic children had the same capacity to spread the virus compared to others who had symptoms of COVID-19.
  • And, a study from Singapore early in the COVID-19 pandemic showed that people who were asymptomatic still were spreading SARS-CoV-2 to others.

Asymptomatic transmission of covid-19

“It’s also unclear to what extent people with no symptoms transmit SARS-CoV-2. The only test for live virus is viral culture. PCR and lateral flow tests do not distinguish live virus. No test of infection or infectiousness is currently available for routine use.678 As things stand, a person who tests positive with any kind of test may or may not have an active infection with live virus, and may or may not be infectious.9

Fomite / Surface Transmission

SARS-CoV-2 disease severity and transmission efficiency is increased for airborne but not fomite exposure in Syrian hamsters. – Dec 28, 2020

 Syrian hamsters are susceptible to SARS-CoV-2 infection through intranasal, aerosol and fomite exposure.

Intranasal and aerosol inoculation caused more severe respiratory pathology, higher virus loads and increased weight loss. Fomite exposure led to milder disease manifestation characterized by an anti-inflammatory immune state and delayed shedding pattern. Early shedding was linked to an increase in disease severity. Airborne transmission was more efficient than fomite transmission and dependent on the direction of the airflow. 

Longitudinal monitoring of SARS-CoV-2 RNA on high-touch surfaces in a community setting – Nov, 2020

Longitudinal swab sampling of high-touch non-porous surfaces in a Massachusetts town during a COVID-19 outbreak from April to June 2020. (8.3 %) surface samples were positive for SARS-CoV-2.

The estimated risk of infection from touching a contaminated surface was low (less than 5 in 10,000), suggesting fomites play a minimal role in SARS-CoV-2 community transmission. 

Infectivity of SARS-CoV-2 and Other Coronaviruses on Dry Surfaces: Potential for Indirect Transmission – Nov 18 – Literature Review (26 studies measuring actual infectivity)

SARS-CoV-2 remains viable on the timescale of days on hard surfaces under ambient indoor conditions. Similarly, the virus is stable on human skin, signifying the necessity of hand hygiene amidst the current pandemic. There is an inverse relationship between SARS-CoV-2 surface persistence and temperature/humidity, and the virus is well suited to air-conditioned environments (room temperature, ~ 40% relative humidity). Sunlight may rapidly inactivate the virus, suggesting that indirect transmission predominantly occurs indoors

Environmental contamination studies evaluated by both RT-PCR and viral culture demonstrated that viable SARS-CoV-2 was not detected in samples from environmental surfaces despite presence of environmental contamination with SARS-CoV-2 RNA.345

The Impact of Pollution on COVID-19 Transmission

  • Aerosol pollution up-regulates ACE-2 (Angiotensin Converting Enzyme 2) and TMPRSS2 (Transmembrane Serine Protease 2) 
  • Overall, there was a significant correlation between aerosol concentration level, ACE-2 expression, and severity of COVID-19 infection
  • Overall, there was a significant correlation between aerosol concentration level, ACE-2 expression, and severity of COVID-19 infection (Paital and Agrawal, 2020)

Vaccines

Why it takes 2 shots to make mRNA vaccines do their antibody-creating best – and what the data shows on delaying the booster dose

From Vaccines to Memory and Back – a great primer on the immune system

Real-time analysis of a mass vaccination effort via an Artificial Intelligence platform confirms the safety of FDA-authorized COVID-19 vaccines – Feb 23 2020

We retrospectively compared the clinical notes of 31,069 individuals who received at least one dose of the Pfizer/BioNTech or Moderna vaccine to those of 31,069 unvaccinated individuals who were propensity matched by demographics, residential location, and history of prior SARS-CoV-2 testing. We find that vaccinated and unvaccinated individuals were seen in the the clinic at similar rates within 21 days of the first or second actual or assigned vaccination dose . Further, the incidence rates of all surveyed adverse effects were similar or lower in vaccinated individuals compared to unvaccinated individuals after either vaccine dose.

Decreased SARS-CoV-2 viral load following vaccination – Feb, 8th 2021

Israeli researchers found a 4-fold decrease in viral load in patients that tested positive for COVID in the 12-28 day window after receiving the first dose of the vaccine.

Interpreting vaccine efficacy trial results for infection and transmission – Feb 28th, 2021

Estimate that one dose of vaccine reduces the potential for transmission by at least 61%, possibly considerably more. Our main findings are as follows: first, that a single cross-sectional comparison of PCR positivity odds between individuals in vaccine vs. control groups provides a relatively accurate estimate, subject to sampling error, of vaccine effectiveness against viral positivity, which is a composite of effects in reducing susceptibility to infection and in reducing duration

Effectiveness of BNT162b2 mRNA Vaccine Against Infection and COVID-19 Vaccine Coverage in Healthcare Workers in England, Multicentre Prospective Cohort Study (the SIREN Study) – Feb 22, 2021

A single dose of BNT162b2 (Pfizer) vaccine demonstrated vaccine effectiveness of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort. This includes the reduction in asymptomatic infection, and applies when the dominant variant in circulation was B1.1.7 – demonstrating effectiveness against this variant.

Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England – April 09, 2021

“Authors characterized the spread of the B.1.1.7 variant in the United Kingdom. They found that the variant is 43 to 90% more transmissible than the predecessor lineage but saw no clear evidence for a change in disease severity, although enhanced transmission will lead to higher incidence and more hospital admissions. Large resurgences of the virus are likely to occur after the easing of control measures, and it may be necessary to greatly accelerate vaccine roll-out to control the epidemic.”

Vaccines vs Variants

COVID Data Tracker – Variant Proportions

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity – March 12, 2021

Antibodies illicited by vaccines are very effective vs most variants, including the UK one. They’e 3-6x less effective vs the Brazil variants, and 25-45x less effective vs the worse SA variants–this was almost the same as how they worked vs the original SARS virus or the bat-version or bat version. Across the board, Moderna seemed to do a bit better than pfizer.

Two doses provided much better protection vs the worrisome variants than 1 did, with most single-dose antibodies having no neutralizing effect vs the worse SA variant, except in patients with prior COVID infection. Similarly, the best results vs the worrisome variants were seen in those with prior COVID infection AND 2 doses, so definitely still get your second dose!

This study was limited to antibody function, but we now have more data on how other parts of the immune system work vs these variants.

Susceptibility of Circulating SARS-CoV-2 Variants to Neutralization – Sinovac * Sinopharm vaccines vs variants. For the CoronaVac vaccine serum samples, we observed a marked decrease in the GMTs in the serum neutralization of B.1.1.7 (by a factor of 0.5; 95% CI, 0.3 to 0.7) and B.1.351 (by a factor of 0.3; 95% CI, 0.2 to 0.4)

Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England – April 09, 2021

“Authors characterized the spread of the B.1.1.7 variant in the United Kingdom. They found that the variant is 43 to 90% more transmissible than the predecessor lineage but saw no clear evidence for a change in disease severity, although enhanced transmission will lead to higher incidence and more hospital admissions. Large resurgences of the virus are likely to occur after the easing of control measures, and it may be necessary to greatly accelerate vaccine roll-out to control the epidemic.”

Manufacturer Updates

Pfizer Update for Adolescents ages 12-15 – Vaccine proved 100% effective in a trial of 2,260 (18 COVID cases in placebo group). Antibody levels were 75% higher than the 16-25 group.

Disease Pathology

Detection of autoimmune antibodies in severe but not in moderate or asymptomatic COVID-19 patients – Initial screening for antinuclear antibodies (ANA) IgG revealed that 1.6% (2/126) and 4% (5/126) of ICU COVID-19 cases developed strong and moderate ANA levels, respectively. However, all the non-ICU cases (n=273) were ANA negative. The high ANA level was confirmed by immunofluorescence (IFA) and large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq).

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates – Understanding immune responses to severe acute respiratory syndrome coronavirus 2 is crucial to understanding disease pathogenesis and the usefulness of bridge therapies, such as hyperimmune globulin and convalescent human plasma, and to developing vaccines, antivirals, and monoclonal antibodies – GREAT GRAPHIC ON COVID LIFECYCLE

COVID Outcomes

Mortality Rates

Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications – Dec, 2020

“Our analysis finds a exponential relationship between age and IFR for COVID-19.

The estimated age-specific IFR is very low for children and younger adults

  • 0.002% at age 10
  • 0.01% at age 25
  • 0.4% at age 55,
  • 1.4% at age 65, 4.6% at age 75, and
  • 15% at age 85.

Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. “

Infection fatality risk for SARS-CoV-2 in community dwelling population of Spain: nationwide seroepidemiological study – Nov, 2020

Seroprevalence study in 61,098 people in Spain, March through June, excluding nursing homes.

  • This study found an infection fatality risk for SARS-CoV-2 of 0.83-1.07% in the community dwelling population of Spain (10x the seasonal influenza)
  • The risk of death was low in infected individuals aged younger than 50, but increased sharply with age, particularly in men
  • In the oldest age group (≥80 years), an estimated 12-16% of infected men and 5-6% of infected women died in Spain during the first wave of the covid-19 pandemic

The higher mortality in men might result from more comorbidities and risk factors (eg, smoking, obesity) than in women, and also differences in cellular immunity between men and women, including poorer T cell activation and an increase in proinflammatory cytokines in men.19

Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study – December, 2020 – Compared hospitalized flu and COVID patients in France.

 In-hospital mortality was higher in patients with COVID-19 than in patients with influenza (15 104 [16·9%] of 89 530 vs2640 [5·8%] of 45 819), with a relative risk of death of 2·9 (95% CI 2·8–3·0) and an age-standardised mortality ratio of 2·82.

Of the patients hospitalised, the proportion of paediatric patients (<18 years) was smaller for COVID-19 than for influenza (1227 [1·4%] vs8942 [19·5%]), but a larger proportion of patients younger than 5 years needed intensive care support for COVID-19 than for influenza (14 [2·3%] of 613 vs 65 [0·9%] of 6973).

In adolescents (11–17 years), the in-hospital mortality was ten-times higher for COVID-19 than for influenza (five [1·1% of 458 vs one [0·1%] of 804), and patients with COVID-19 were more frequently obese or overweight.

Comorbidities

Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors. PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

Interventions

Vitamin D

COVID/Vitamin D: Much More Than You Wanted To Know – An opinion article with the following conclusions:

Here are my beliefs after doing this research:

Does Vitamin D significantly decrease the risk of getting COVID?: 25% chance this is true. The Biobank and Mendelian randomization studies are strong arguments against this; the latitude, seasonal, and racial differences are only weak evidence in favor.

Does Vitamin D use at a hospital significantly improve your chances?: 25% chance this is true. I trust the large Brazilian study more than the smaller Spanish one, but aside from size and a general bias towards skepticism I can’t justify this very well. 

Do the benefits of taking a Vitamin D supplement at a normal dose equal or outweigh the costs for most people?: 75% chance this is true. The risks are pretty low, and it will probably bring you closer to rather than further from a natural range if you’re a modern indoor worker (side effects are few; the most serious is probably kidney stones, so don’t take it if you have any tendency towards that). And maybe some day, after countless false leads and stupid red herrings, one of the claims people make about this substance will actually pan out. Who knows?

Other Treatments

Decoy Protein – Rodent Study – “We envision this soluble ACE2 protein will attenuate the entry of coronavirus into cells in the body mainly in the respiratory system and, consequently, the serious symptoms seen in severe COVID 19,”

Other

Animal Models in COVID-19 – Nature Review

Do an Altered Gut Microbiota and an Associated Leaky Gut Affect COVID-19 Severity? – summarizes the accumulating evidence that supports the hypothesis that an altered gut microbiota and its associated leaky gut may contribute to the onset of gastrointestinal symptoms and occasionally to additional multiorgan complications that may lead to severe illness by allowing leakage of the causative coronavirus into the circulatory system.

Master Question List for COVID-19 (caused by SARS-CoV-2) – DOD FAQ with over 700 references.

Global.health Google Database of over 5 million COVID cases for research purposes