Useful COVID Studies

Can the USA return to pre-COVID-19 normal by July 4? – June 02, 2021

Modeling showing that relaxing all social distancing guidelines on July 4th would have little impact for vaccinated people, but relaxing guidelines for the unvaccinated could lead to another surge comparable to the first one. Returning to 70% of pre-COVID social activity could limit this.

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.

CDC Science Brief: Background Rationale and Evidence for Public Health Recommendations for Fully Vaccinated People – This provides a great overview of the current body of research on vaccine efficacy.


Debiasing Covid-19 prevalence estimates

The usefulness of antigen testing in predicting contagiousness in COVID-19 – October 18, 2021

The antigen test was 100.0% specific but only 40.9% sensitive for diagnosing infection compared to RT-PCR. Interestingly, SARS-CoV-2 contagiousness is highly unlikely with a negative antigen test since it exhibited a negative predictive value of 99.9% than viral culture. Furthermore, a cycle threshold (Ct) value of 18.1 in RT-PCR was shown to be the one that best predicts contagiousness (AUC 97.6%). Thus, screening people with antigen testing is a good approach to prevent SARS-CoV-2 contagion and allow returning to daily activities.

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

A Year In, Here’s What We Know About Vitamin D For Preventing COVID

How long will the coronavirus vaccines protect you? Experts weigh in – March 29th


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


Mask Effectiveness for Preventing Secondary Cases of COVID-19, Johnson County, Iowa, USA – Oct 12, 2021

 Mask use by both parties reduced the SAR by half, from 25.6% to 12.5%. Longer exposure duration significantly increased SARs

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).


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)

Public Transit Risks


Laboratory Modeling of SARS-CoV-2 Exposure Reduction Through Physically Distanced Seating in Aircraft Cabins Using Bacteriophage Aerosol — November 2020

Based on laboratory modeling of exposure to SARS-CoV-2 on single-aisle and twin-aisle aircraft, exposures in scenarios in which the middle seat was vacant were reduced by 23% to 57%, compared with full aircraft occupancy, depending upon the model. Didn’t take masking into account.


Vaccines Prevent Transmission

US CDC Compendium of Vaccine Effectiveness Studies by Date

Vaccines vs Transmission – Useful Compendium Table of Studies

Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines – June 30th

Study of 3975 health care personnel, first responders, and other essential and frontline workers. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7).

Decreased infectivity following BNT162b2 vaccination: A prospective cohort study in Israel – August, 2021

BNT162b2 was 65% effective in preventing infections following exposures, and 83% effective in preventing never-symptomatic, infectious (N-gene Ct value<30) infections, and that viral load, was significantly lower in vaccinated vs. unvaccinated infected HCW. The mean Ct-value was significantly higher in vaccinated vs. unvaccinated (27.3±1.2 vs. 22.2±1.0, p<0.001

BNT 13b2 Pfizer vaccine protects against SARS-CoV-2 respiratory mucosal colonization even after prolonged exposure to positive family members – March 31, 2021

14 vaccinated healthcare workers didn’t get sick, even when consistently exposed to sick family members.

Which is better: Vaccines or Natural Infection?

Antibody response to SARS-CoV-2 infection and BNT162b2 vaccine in Israel – July 8th, 2021

In this study, we analyzed serum Spike protein-specific IgG antibodies from 26,170 samples, including convalescent individuals who had coronavirus disease 2019 (COVID-19) and recipients of the BNT162b2 vaccine. Vaccinated individuals had the highest antibody levels, nearly three times higher than that of convalescent individuals recovering from symptomatic COVID-19 (Wilcox P < 0.001).

Nearly all vaccinated individuals were seropositive six days or more after the second dose (99.4%), while patients recovering from symptomatic COVID-19 were only mostly seropositive (75.7%) (RR=1.31; Chisq P<2.9e-36) (Fig 2).

the difference in antibody levels between the symptomatic and asymptomatic groups is generally insignificant in ages 30 or younger (Kruskal P=0.44), but becomes highly significant in ages 30 and older (Kruskal P=7.1e-11).

How Long does Immunity Last?

Immunity to SARS-CoV-2 up to 15 months after infection – Oct 11, 2021

Following a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8- fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months.

What do we Know About Breakthrough Infections

BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel – July 6, 2021

A total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19

Which Dosing Interval is Best?

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine – October 15th, 2021

  • BNT162b2 vaccine with an extended interval between doses is highly protective
  • Antibody levels were higher after the extended regimen compared with the short regimen
  • The extended regimen enriches for virus-specific CD4+ T cells expressing IL-2
  • Antibody levels wane after each dose, but B and T cell pools are maintained


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 & Disease Severity

Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines – June 30th

mRNA Vaccines adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7).

Vaccines vs Variants

COVID Data Tracker – Variant Proportions

Omicron SubVariants

BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection – June 17th

 BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.

Neutralization of the SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants – June 15, 2022

As compared with the response against the ancestral SARS-CoV-2 strain bearing the D614G mutation, neutralizing-antibody titers were 4.1 times as low against the BA.4/5 variant and 3.2 times as low against the BA.2.12.1 variant (P<0.001 for both comparisons), and the titers were approximately 2.8 times as low against the BA.1 and BA.2 variants


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.”

COVID-19 pandemic dynamics in India and impact of the SARS-CoV-2 Delta (B.1.617.2) variant – June 25th

Combining the model-inference estimates during the first and second pandemic waves in India, we estimated that Delta was able to escape immunity from prior wildtype infection 45.8% (95% CI: 0 – 67.6%) of the time and was 60.1% (95% CI: 46.0 – 80.8%) more infectious than wildtype SARS-CoV-2.

Delta / B.1.617 Variant from India

Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021  – October, 2021commenting unavailable

Prevention of severe disease and hospitalisation

The VE against the compound outcome severe disease was assessed in three studies (one cohort, two test-negative design). They were performed in three countries (Table 2) [8,13,18]. The VE estimates ranged from 81.5% to 100% and the pooled VE was 93.8% (95% CI: 83–98; I2 = 0%; Supplement Part S6). Hospitalisation was reported in four studies: two cohort studies, one test-negative design study and one analysis of cross-sectional serial samples (Table 2). The studies were performed in the US and the UK [57,20]. Single study VE ranged between 75% and 96%. Pooled VE against hospitalisation was 90.9% (95% CI: 84.5–94.7; I2 = 18.5%; Figure 2 B). No study reported admission to intensive care unit, intubation or death.Effectiveness against Delta variant compared with Alpha variant

In nine studies, VE estimates against infections with the Delta variant were compared with those against infections with the Alpha variant in the same study for at least one outcome (Tables 1 and 2). Overall, VE against Delta was 10–20% lower than VE against Alpha for less severe outcomes. For hospitalisation, VE against Delta did not differ from VE against Alpha.Waning protection

Two cohort studies from the US investigated VE against infections (symptomatic or asymptomatic) for more than one time point after vaccination. One study reported a decrease of protection offered by the Comirnaty vaccine from 93% (95% CI: 85–97) at baseline to 53% (95% CI: 39‒65) after at least 4 months [7]. The other study investigated protection conferred by any FDA-licensed vaccines in frontline workers (healthcare workers and others) and reported a non-significant change from 85% (95% CI: 68–93) to 73% (95% CI: 49–86) after at least 5 months following full vaccination [19].

Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India – May 3, 2021

It has 8 spike protein mutations, 2 are linked to increased transmissibility, and one is the same that may have let the P.1. variant from Brazil evade immunity

SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination – May 5, 2021

Antibodies from previously infected patients and from Pfizer vaccinated ones showed 50% and 67% less neutralizing ability, respectively.

SARS-CoV-2 B.1.617 emergence and sensitivity to vaccine-elicited antibodies – May 9, 2021

80% drop in neutralizing activity from the Pfizer vaccine.

Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees – April 22, 2021

Sera from the Covaxin vaccine being distributed in india does work well against this variant!

Delta variant: What is happening with transmission, hospital admissions, and restrictions? – June 15th, 2021

Quick summary of Delta as of this date. 60% more transmissible than Alpha, leading to more cases of hospitalizations. More replication in airways. Increased severity and relative impact on children still unclear.

Covid-19: Delta variant is now UK’s most dominant strain and spreading through schools – June 4th, 2021

Latest data from the Office for National Statistics for the week to 29 May show that numbers of cases of covid-19 have been rising fastest in schoolchildren in years 7 to 11.

Effectiveness of COVID-19 vaccines against the B.1.617.2 variant – May 24th, 2021

mRNA vaccines 88% vs symptomatic disease, 96% vs hospitalizations. AstraZeneca 60% and 92%.

Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination – June 3, 2021

One vaccine dose not nearly as effective as 2 doses, compared to alpha variant.

SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 17 – 25 June 2021

Great overview of Delta data from the UK. Severity, hospitalizations, transmission, etc. Maybe 80% vaccine protection vs transmission.

Epsilon Variant (

SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern – July 01, 2021

The neutralizing potency of the plasma against the Epsilon variant of concern was reduced about 2 to 3.5 fold. Another study showed similar results, along with early data for increased transmissibility.

Lambda / C.37

First discovered in Peru in December, 2020.

SARS-CoV-2 Lambda Variant Remains Susceptible to Neutralization by mRNA Vaccine-elicited Antibodies and Convalescent Serum – June 03, 2021

Virus with the lambda spike had higher infectivity and was neutralized by convalescent sera and vaccine-elicited antibodies with a relatively minor 2.3-3.3-fold decrease in titer on average. The virus was neutralized by the Regeneron therapeutic monoclonal antibody cocktail with no loss of titer. The results suggest that vaccines in current use will remain protective against the lambda variant and that monoclonal antibody therapy will remain effective.

Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda – July 6th, 2021

Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant.

Epsilon – B.1.427

SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern – July 1st

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant – June 24th

Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively.

Manufacturer Updates

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

Novavax Clinical Trial Results – June 14th, 2021

90.4% overall efficacy (primary endpoint) 91% efficacy in “high-risk” populations 93.2% efficacy against Variants of Interest/Concern 100% protection against moderate & severe disease.

Vaccine Side Effects

CDC Myocarditis & Pericarditis Guidelines

Heart-inflammation risk from Pfizer COVID vaccine is very low

Two studies from Israel quantify the risk of myocarditis following the Pfizer–BioNTech shot, with one suggesting the chance of developing the condition is about one in 50,000.

VSafe myocarditis data. 277 cases in ages 16-24. 35/million in ages 16-17 vs 2-19 expected, 20.6/million in 18-24 vs. 8-83 expected. 81% recovered fully, the rest still ongoing. Population data comes from here.

Reinfection Risk & Outcomes

Outcomes of SARS-CoV-2 Reinfection – June 20, 2022

Cumulative risks of negative health outcomes get worse each time you’re infected with COVID.

Compared to those with first infection, those with reinfection exhibited an increased risk of all-cause mortality (Hazard Ratio (HR) 2.14; 95% confidence interval (CI): 1.97, 2.33) and excess burden of all-cause mortality estimated at 23.8 (95% CI: 18.9, 29.2) per 1000 persons at 6 months; all burden estimates represent excess burden and are given per 1,000 persons at 6 months (Fig. 1, Supplemental Table 3). People with a reinfection also had an increased risk of hospitalization (HR 2.98 (2.83, 3.12); burden of 95.47 (89.17, 102.03)), and having at least one sequela of SARS-CoV-2 infection (HR 1.82 (1.78, 1.88); burden of 196.2 (186.57, 205.87)) (Fig. 1, Supplemental Table 3).

The median distribution of time between the first and second infection was 79 days (IQR: 48–119), and between the second and third was 65 (43–97).


Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2 – June 18, 2022

Omicron cases were less likely to experience long COVID for all vaccine timings, with an odds ratio ranging from 0·24 (0·20–0·32) to 0·50 (0·43–0·59). T

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

Disease Severity Depends on Infectious Dose

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19 – August 23, 2021

Monkey trial that showed disease severity is related to dose that they were exposed to.

Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors – June, 2021

COVID survivors showed a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population. Telomere lengths were ~3x longer in the No-COVID group.


CDC’s Guidance for Schools – July 9th

COVID Outcomes

Outcomes in Children

Epidemiology and Outcomes of SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome in Children vs Influenza Among Critically Ill Children – June 15, 2022

More children were admitted per center per quarter with SARS-CoV-2 disease than with influenza (median [IQR], 2.8 [1.4-9.6] vs 2.4 [0.9-4.0]; P < .001). Children with SARS-CoV-2 disease had higher risk of mortality, but actual mortality did not differ (Table).

Per quarter, there were twice as many mean admissions from SARS-CoV-2–related disease as influenza, and one-third more children received endotracheal intubation (Figure, A). PICU and hospital length of stay were significantly longer with SARS-CoV-2–related disease (Figure, B). Similar patterns were observed in children with and without identified comorbidities.

Absence of public health measures when SARS-CoV-2 variants similar to the original and Alpha strains are in circulation would likely lead to a volume of critical illness and death in unimmunized children that is markedly higher than what is typically seen with influenza.

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.


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.


Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review – June 06, 2021

We identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals). Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures during the three trimesters of pregnancy.

The most frequent exposure was to AS03 adjuvant in the context of A/H1N1 pandemic influenza vaccines (n=24), followed by aluminum-based adjuvants (n=11). Only one study reported exposure to messenger RNA (mRNA) from Pfizer & Moderna COVID-19 vaccines that also used lipid nanoparticles.

This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines that were selected for review by the COVAX MIWG in August 2020 or of their components or platforms when used in other vaccines. 

Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons – April 21st, 2021

Analysis of over 8,000 pregnant women–Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines.

COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes – May 2, 2021

This systematic review supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.

Women’s views on accepting COVID-19 vaccination during and after pregnancy, and for their babies: A multi-methods study in the UK – May 3rd

Contains lots of useful citations on the state of the research around COVID, vaccines, and pregnancy.

COVID-19 Vaccine Considerations during Pregnancy and Lactation – Received Dec 29th, 2020

Another useful overview of the state of the research at the end of 2020 and how to think about the decision.

Perinatal SARS-CoV-2 Infection and Neonatal COVID-19: A 2021 Update – May, 2021

A thorough review of the interplay between COVID-19 and pregnancy.

SARS-CoV-2 in first trimester pregnancy: a cohort study – December 28, 2020

No increased risk found in COVID patients with a first trimester pregnancy.

Maternal death related to COVID‐19: A systematic review and meta‐analysis focused on maternal co‐morbidities and clinical characteristics – April 30th, 2021

Added comorbidities significantly increase risk

Ovarian follicular function is not altered by SARS-Cov-2 infection or BNT162b2 mRNA Covid-19 vaccination – April 13th, 2921

No negative effects found in the ovaries, either due to COVID or to vaccination.

Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination – March 12, 2021

Antibodies from vaccines transfer to newborn babies.

SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women – April 13th, 2021

Covid-19 Vaccines, Pregnancy & Fertility – Updating resource, great list of studies on pregnancy an COVID.

Does mRNA SARS-CoV-2 vaccine influence patients’ performance during IVF-ET cycle? – May 13, 2021

Thirty-six couples resumed IVF treatment 7–85 days after receiving mRNA SARS-CoV-2 vaccine. No in-between cycles differences were observed in ovarian stimulation and embryological variables before and after receiving mRNA SARS-CoV-2 vaccination.

Long-Term Effects

Cardiac Outcomes

Prospective Case-Control Study of Cardiovascular Abnormalities 6 Months Following Mild COVID-19 in Healthcare Workers – May, 2021

Matched cohort of 149 participants found no negative cardiac outcomes in MRI or blood testing over 6-months.


Vitamin D

The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis – July 29th, 2021

Twenty-three studies containing 11 901 participants entered into the meta-analysis. This study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin-D-deficient individuals and about five times higher probability of developing the severe disease in vitamin-D-deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

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


Paxlovid loses luster in people who aren’t at high risk from Covid-19, Pfizer study finds – June 15 – News article about Pfizer press release / study. Low risk cohort. Vaccinated 18+ with one comorbidity. No statistically significant benefit found, but underpowered study.

  • Five people of 576 taking Paxlovid were hospitalized or died during the study, compared with 10 of 569 taking the placebo; there were no deaths in patients taking Paxlovid but one in the placebo group.
  • Among fully vaccinated participants, three of 361 taking Paxlovid were hospitalized or died, compared with seven of 360 on the placebo.
  • There was a 72% reduction in days spent in the hospital in people taking Paxlovid compared with those on a placebo.
  • No patients taking Paxlovid were admitted to intensive care, compared with three in the placebo group.

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,”

Molnupiravir vs Paxlovid

Societal Impact

Productivity gains from teleworking in the post COVID-19 era : How can public policies make it happen? – September, 2020

Covers data and strategies for maximizing worker productivity through the combination of telework and in-person work.


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