Covid-19 vaccines don't raise miscarriage risk, three studies show

Pregnant women who received at least one dose of a COVID-19 vaccine were not at higher risk for miscarriage than their unvaccinated counterparts, according to a trio of new US studies:

Miscarriage no more likely in vaccinated: In the first study, published yesterday in JAMA, researchers from the Vaccine Safety Datalink (VSD) surveillance network used diagnostic and procedure codes and electronic health records to identify and assign gestational ages of miscarriages and ongoing pregnancies from Dec 15, 2020, to Jun 28, 2021... Read here.

More evidence of vaccine safety in pregnancy: Similarly, in a letter yesterday in the New England Journal of Medicine (NEJM), CDC scientists enrolled 2,456 women who were part of the agency's COVID-19 vaccine safety pregnancy registry... Read here.

A revised risk estimate: And in response to a letter yesterday in NEJM, a separate group of CDC researchers updated its analysis of 2,456 pregnant women who received one or two doses of an mRNA COVID-19 vaccine before conception or 20 weeks' gestation... Read here.

Read here (Center for Infectious Disease Research and Policy, Sept 9, 2021)

Covid-19: Pfizer BioNTech vaccine reduced cases by 94% in Israel, shows peer reviewed study

‘The Pfizer BioNTech coronavirus vaccine produces as good results in the “real world” as have been previously documented in randomised trials.

‘A case control study, which has been peer reviewed and published in the New England Journal of Medicine, compared 596 618 people who were newly vaccinated in Israel and matched them to unvaccinated controls.1 Two doses of the mRNA vaccine reduced symptomatic cases by 94%, hospitalisation by 87%, and severe covid-19 by 92%, according to the data from the Clalit Institute for Research which is Israel’s biggest healthcare provider.

‘Researchers recorded the outcomes at three periods: days 14 to 20 after the first dose of vaccine, days 21 through 27 after the first dose, and day 7 after the second dose. In Israel, the second dose of vaccine is given on day 21 in line with the trials and the manufacturer’s recommendation. The UK is leaving a 12 week gap between doses.

‘During a mean follow-up of 15 days, 10 561 infections were documented of which 5996 were symptomatic covid-19 illness, 369 required hospitalisation, 229 were severe cases, and 41 resulted in death.

‘After one dose, during days 14 to 20, the vaccine effectiveness was 57% for symptomatic covid-19, 74% for hospitalisation, and 62% for severe disease. The estimated effectiveness in preventing death from covid-19 was 72% in the two to three weeks after the first dose. There was insufficient data to produce an estimate on the reduction in mortality in those who received two doses.

‘The study took place from 20 December 2020, when Israel’s national vaccination drive was launched, to 1 February 2021. It coincided with Israel’s third and largest wave of coronavirus infection and illness.’

Read here (BMJ, Feb 25, 2021)

• BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting

Read original study here (New England Journal of Medicine, Feb 24, 2021)

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

‘It is important to note that all the severe Covid-19 cases were in the placebo group, which suggests that mRNA-1273 is likely to have an effect on preventing severe illness, which is the major cause of health care utilization, complications, and death. The finding of fewer occurrences of symptomatic SARS-CoV-2 infection after a single dose of mRNA-1273 is encouraging; however, the trial was not designed to evaluate the efficacy of a single dose, and additional evaluation is warranted.

‘Overall, the safety of the mRNA-1273 vaccine regimen and platform is reassuring; no unexpected patterns of concern were identified. The reactogenicity associated with immunization with mRNA-1273 in this trial is similar to that in the phase 1 data reported previously. Overall, the local reactions to vaccination were mild; however, moderate-to-severe systemic side effects, such as fatigue, myalgia, arthralgia, and headache, were noted in about 50% of participants in the mRNA-1273 group after the second dose. These side effects were transient, starting about 15 hours after vaccination and resolving in most participants by day 2, without sequelae.’

Read here (New England Journal of Medicine, Feb 4, 2020)

A new vaccine to battle Covid-19 -- NEJM editorial

‘That the mRNA-1273 Covid-19 and the BNT162b2 Covid-19 vaccines protect with near-identical 94 to 95% vaccine efficacies — and that both vaccines were developed and tested in less than a year — are extraordinary scientific and medical triumphs. This happened because the scientific community was prepared from years of technology development for other vaccines, such as those against HIV, influenza, respiratory syncytial virus, and Zika, and because clinical trials consortia were established that rapidly carried out Covid-19 efficacy trials. If mRNA-LNP vaccines significantly contribute to control of the pandemic, mRNA technology has the potential to radically change vaccine design for future viral outbreaks.

‘Although the Covid-19 pandemic is currently raging, the prospects for control of this and future pandemics are bright. The recent FDA issuance of EUAs for these extraordinarily protective vaccines provide us with much-needed hope at a time when so many are suffering. The next challenge is to get these and the next Covid-19 vaccines to the people most at risk as quickly as possible.’

Read here (New England Journal of Medicine, Feb 4, 2020)

Covid-19 vaccine — Frequently asked questions

Paul Sax, M.D., a Professor of Medicine at Harvard Medical School and an infectious disease specialist, provides concise and engaging answers to clinicians’ questions about Covid-19 vaccination and to the questions and concerns patients will raise.

Read here (New England Journal of Medicine, as at Jan 18, 2021)

Early high-titer plasma therapy to prevent severe Covid-19 in older adults

‘Background: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

‘Methods: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.

‘Results: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.

‘Conclusions: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19.’

Read here (NCBI-New England Journal of Medicine, Jan 6, 2021)

Early high-titer plasma therapy to prevent severe Covid-19 in older adults (New England Journal of Medicine, Jan 6, 2021)

‘We report the use of convalescent plasma in older adult patients early in the course of Covid-19. The administration of convalescent plasma with high titers of antibodies against SARS-CoV-2 to infected patients within 72 hours after the onset of symptoms reduced the risk of progression to severe respiratory disease by 48%. Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary end points. Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection...

‘In our randomized, controlled trial, the administration of high-titer convalescent plasma against SARS-CoV-2 to infected older adults within 72 hours after the onset of mild symptoms reduced the progression of Covid-19 to severe illness. This simple and inexpensive intervention can reduce demands on the health care system and may save lives. Early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.’

Read here (New England Journal of Medicine, Jan 6, 2021)

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine (Pfizer clinical trial)

BACKGROUND: ‘Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.’

METHODS: ‘In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.’

RESULTS: ‘A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.’

CONCLUSIONS: ‘A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728. opens in new tab.)’

Read here (New England Journal of Medicine, Dec 31. 2020)

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

‘This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.

‘The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline... 

‘The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427. opens in new tab.)’

Read here (New England Journal of Medicine, Dec 30, 2020)

Covid outbreak data on US carrier shows a plethora of initial symptoms among the symptomatic, only 5.3% fever : NEJM

‘Among the crew members who had symptomatic Covid-19 (confirmed or suspected), headache was the most common symptom reported at any point during illness (occurring in 68.0%), followed by cough (59.5%), nasal or sinus congestion (43.8%), and altered sense of taste or smell (42.3%) (Figure 3). The predominant symptoms reported at the onset of illness were cough (32.8%), headache (31.0%), and altered sense of taste or smell (24.1%). Shortness of breath at any point during illness was reported by 20.3% of the crew members with symptomatic cases, and 7.0% noted shortness of breath as an initial presenting symptom. In addition, 26.2% of the crew members with symptomatic Covid-19 reported chest pain or chest pressure at some point during their illness. Fever was reported as an initial presenting symptom by 5.3% of the crew members with symptomatic Covid-19, and fever at any point during illness was reported by 13.2%. Measured temperature readings showed that 2.8% of the crew members who had Covid-19 had a recorded temperature of 100.0°F or above, as compared with 0.3% of the crew members who did not have Covid-19. Among the crew members with Covid-19 for whom pulse oximetry data were available, approximately 0.5% had readings below 95% while breathing ambient air, with 0.08% below 94% and none below 90%.’

Read here (New England Journal of Medicine, Nov 11, 2020) 

NEJM paper on Iceland throws into question Imperial College team results: Antibodies stable after 4 months. Also death rate 0.3%, 44% not diagnosed

‘Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.‘

Read here (NEJM, Oct 29, 2020)

Read here the BBC story on Imperial College study that says antibodies drop rapidly  

People with blood-group A more susceptible to severe Covid-19

‘Using a pragmatic approach with simplified inclusion criteria and a complementary team of clinicians at the European Covid-19 epicenters in Italy and Spain and scientists in the less-burdened countries of Germany and Norway, we performed a GWAS that included de novo genotyping for Covid-19 with respiratory failure in approximately 2 months. We detected a novel susceptibility locus at a chromosome 3p21.31 gene cluster and confirmed a potential involvement of the ABO blood-group system in Covid-19.’

Read here (New England Journal of Medicine, Oct 15, 2020) 

Dying in a leadership vacuum: NEJM editorial

‘Covid-19 has created a crisis throughout the world. This crisis has produced a test of leadership. With no good options to combat a novel pathogen, countries were forced to make hard choices about how to respond. Here in the United States, our leaders have failed that test. They have taken a crisis and turned it into a tragedy.

‘The magnitude of this failure is astonishing. According to the Johns Hopkins Center for Systems Science and Engineering,1 the United States leads the world in Covid-19 cases and in deaths due to the disease, far exceeding the numbers in much larger countries, such as China. The death rate in this country is more than double that of Canada, exceeds that of Japan, a country with a vulnerable and elderly population, by a factor of almost 50, and even dwarfs the rates in lower-middle-income countries, such as Vietnam, by a factor of almost 2000. Covid-19 is an overwhelming challenge, and many factors contribute to its severity. But the one we can control is how we behave. And in the United States we have consistently behaved poorly.’

Read here (New England Journal of Medicine, Oct 8, 2020)

Covid-19 and health equity — Time to think big

To achieve health equity, we need to reach beyond the health care system — and think big. New social policies on a few key fronts could advance both health equity and the Covid-19 response.

• First, we propose establishing a universal food income.
• Second, we recommend reforming unemployment insurance.
• Finally, we need policies supporting investment in community development.

Read here (New England Journal of Medicine,  Sept 17, 2020)

The new stability

‘I look for hope and find none, but I am not allowed to admit to total free fall. “Stronger together” say the screen savers on every screen in the hospital, the banners on the sides of the shuttle bus. What I’ll see in the coming weeks is just how much this isn’t true, how so many of our sickest patients are Black or Brown like you, “essential” and yet unprotected. I will see a 46-year-old Black man, infected with SARS-CoV-2, die instead from having a police officer kneel on his neck. I will see those who protest police brutality, though masked and mostly peaceful, tear-gassed and shot with rubber bullets. I will see unregulated corporate bailouts, record unemployment, record housing insecurity. I will see political polarization recast common-sense public health policy as liberal propaganda. I will see your death multiplied by 10,000, by 100,000, all those bodies, mothers and fathers, daughters and sons. I wish I could tell you how sorry I am, for my fear, for our nation, for what happens next.’

Read here (New England Journal of Medicine, July 17, 2020)

Lancet editor spills the beans and the unfolding of a pharmaceutical scandal

‘In a videotaped interview on May 24, 2020, Dr [Philippe] Douste-Blazy provided insight into how a series of negative hydroxychloroquine studies got published in prestigious medical journals. He revealed that at a recent Chatham House top secret, closed door meeting attended by experts only, the editors of both, The Lancet and the New England Journal of Medicine expressed their exasperation citing the pressures put on them by pharmaceutical companies... [Douste-Blazy is a cardiologist and former French Health Minister who served as Under-Secretary General of the United Nations. He was a candidate in 2017 for Director of the World Health Organization]

‘The alarming findings and serious negative impact of the Lancet report led numerous scientists around the globe to scrutinise the report in detail. That scrutiny by legitimate, independent scientists has led to many serious questions about the integrity of the study, the authenticity of the data, and the validity of the methods the authors used... [many details are provided in this story]

Demonisation of favourable HCQ-AZ treatment studies: ‘Since publishing favourable reports about a treatment combination of two cheap, widely prescribed medicines: hydroxychloroquine and the antibiotic azithromycin, as a treatment of choice against Covid-19, Dr [Didier] Raoult has become the subject of intense demonisation by the corporate-influenced medical establishment, the media, and the [sic] who resort to this tactic whenever they lack evidence or legitimate grounds to support public health policies that cause people harm.’

Read here (Health Impact News, received on June 13, 2020)

The pandemic's first major research scandal erupts

‘The controversy is an unfortunate distraction, says Miguel Hernán, a Harvard epidemiologist and co-investigator on an ongoing trial of hydroxychloroquine in Spain and Latin America. “If you do something as inflammatory as this without a solid foundation, you are going to make a lot of people waste time trying to understand what is going on.” Chaccour says both NEJM and The Lancet should have scrutinized the provenance of Surgisphere's data more closely before publishing the studies. “Here we are in the middle of a pandemic with hundreds of thousands of deaths, and the two most prestigious medical journals have failed us,” he says.’

Read here (Science Magazine, June 5, 2020)

Death from Covid-19 of 23 health care workers in China

‘As of March 31, none of the 42,600 health care workers who went to Hubei Province to care for patients with Covid-19 were known to have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).5 The 42,600 workers included one of us, an intensive care physician from Fujian Province who cared for patients with Covid-19 from January 29 to March 23, first in Wuhan Central Hospital, and then in Wuhan Jinyintan Hospital. These data suggest that sufficient precautions with rigorous enforcement can prevent health care workers from becoming infected with SARS-CoV-2 and the subsequent risk of death.’

Read here (New England Journal of Medicine, June 4, 2020)

Governments and WHO changed Covid-19 policy based on suspect data from tiny US company

‘The World Health Organization and a number of national governments have changed their Covid-19 policies and treatments on the basis of flawed data from a little-known US healthcare analytics company [Surgisphere], also calling into question the integrity of key studies published in some of the world’s most prestigious medical journals [The Lancet and New England Journal of Medicine].

‘Data it claims to have legitimately obtained from more than a thousand hospitals worldwide formed the basis of scientific articles that have led to changes in Covid-19 treatment policies in Latin American countries. It was also behind a decision by the WHO and research institutes around the world to halt trials of the controversial drug hydroxychloroquine. On Wednesday, the WHO announced those trials would now resume.’

Read here (The Guardian, June 3, 2020)

Harnessing our humanity — How Washington’s health care workers have risen to the pandemic challenge

‘Given mounting PPE shortages and the rising death toll from Covid-19 among health care workers globally, such scenarios [of protocol modifications -- including the use of bandannas in place of face masks] induce terror and necessitate rethinking of routine standards of care. Should we run to codes of patients with known or suspected Covid-19? Should physicians refuse to intubate a patient unless they have adequate PPE? Should we offer bedside comfort to the elderly patient with possible Covid-19 who becomes increasingly delirious as unrecognizable health care workers speed in and out of the room while TV coverage of the pandemic drones on in the background? The clarion call of the profession — to put our patients’ needs above our own — is far less directive when meeting one patient’s needs may leave us too ill to care for the next.’

Read here (New England Journal of Medicine, May 28, 2020)