Coronavirus (Covid-19)

Conventional wisdom is that previous infection with omicron subvariant BA.1 or BA.2 does not protect against BA.5, but data from Portugal show considerable protection against BA.5 infection from previous BA.1 or BA.2 infection.

In this trial involving overweight or obese outpatients with Covid-19, investigators found that none of three repurposed drugs (metformin, ivermectin, and fluvoxamine) reduced the risk of serious disease.

During the 2022 clinical rollout of nirmatrelvir in Israel, most patients (78%) had previous SARS-CoV-2 immunity. Benefit was seen in patients at highest risk for Covid-19 progression, such as those 65 years of age or older.

In this ongoing household cohort study in Nicaragua, previous SARS-CoV-2 infection during a second Covid-19 wave provided some protection against symptomatic Covid-19, with greater protection against severe illness.

The proliferation of vaccine misinformation and its use for political purposes are placing a large number of people at risk in the Covid-19 pandemic and allowing the pandemic to continue.

Outpatients with Covid-19 were followed serially with frequent PCR and viral-culture assessments. The SARS-CoV-2 omicron (BA.1) variant could be cultured a median of 8 days after symptom onset or the initial positive test.

Two doses of the BNT162b2 vaccine were associated mainly with low-grade local adverse effects that lasted 2 days or less and afforded nearly 50% protection against omicron infection and symptomatic illness, which was lower than that seen against delta. Greater protection in the youngest group was noted.

In a small trial of boost immunization with the mRNA vaccine originally received or with heterologous boosting with spike proteins from the original strain or the beta variant, the beta-adjuvanted booster resulted in the highest titers of antibody and activated T cells 2 weeks later.

In a small study involving 54 participants, omicron subvariants BA.2.12.1, BA.4, and BA.5 of SARS-CoV-2 were more likely to escape neutralizing antibodies induced by both vaccination and previous infection than were the prior omicron subvariants BA.1 and BA.2.

In this retrospective cohort study involving pregnant women, those who had been vaccinated against Covid-19 did not have a higher risk of clinically serious adverse events than those who were unvaccinated.

Adult influenza vaccination rates decreased in states with below-average Covid-19 vaccination rates, a finding that raises the possibility that mistrust in Covid-19 vaccines adversely affected influenza vaccination.

After two doses of mRNA vaccine, health care workers had less viral neutralizing-antibody activity against the BA.4/5 and BA.2.12.1 omicron subvariants than against the BA.1 and BA.2 subvariants, but titers increased significantly with a booster dose.

In this report, the evolution of SARS-CoV-2 in response to immunologic and monoclonal-antibody pressure is explored in five patients with B-cell deficiency.

Among persons vaccinated with the adenovirus-based vaccine who received a booster dose of an mRNA vaccine, protection against the omicron variant was assessed. A single booster dose of an mRNA vaccine in recipients of a single priming dose of Ad26.COV2.S provided protection close to that of a three-dose mRNA vaccine regimen.

In part 1 of a phase 2–3 trial, a 50-μg dose of mRNA-1273 vaccine was safe and immunogenic. In part 2, nearly 4000 6-to-11-year-olds received two doses of vaccine or placebo and were followed for a median of 82 days. The vaccine had mainly mild adverse effects and was immunogenic in 99%, similar to the results in 18-to-25-year-olds. Vaccine efficacy during a delta-variant period was 88%.

A small study assessed the neutralization of pseudoviruses composed of the recombinant deltacron and omicron BA.3 variants. BA.3 did not show broad cross-resistance, but deltacron was largely resistant to immune response elicited either by three doses of mRNA vaccines or by previous infection.

ZF2001 contains a tandem-repeat dimeric receptor-binding domain of the SARS-CoV-2 spike protein with aluminum hydroxide adjuvant. In a phase 3 trial, 28,904 participants in five countries were randomly assigned to receive three doses of ZF2001 or placebo. After 6 months of follow-up, efficacy was 76% against infection, 87% against critical or severe disease, and 86% against death. Most side effects were local, low-grade, and transient.

With the emergence of the omicron variant of SARS-CoV-2 in November 2021, these investigators found how rapidly it had spread across Canada among both vaccinated and unvaccinated persons.

In this trial involving more than 24,000 participants, the efficacy of two doses of a viruslike-particle, plant-based vaccine with adjuvant was 69.5% against symptomatic Covid-19 and 78.8% against moderate-to-severe disease. More than 80% of vaccine recipients had local or systemic adverse effects, which were generally mild and short-lived.

In Israel, the use of a fourth dose of BNT162b2 vaccine was initiated on January 3, 2022. As of February 18, a fourth dose produced a 45% reduction in the incidence of infection, a 55% reduction in symptomatic infection, a 68% reduction in hospitalization, and a 74% reduction in Covid-19–related death 7 to 30 days after vaccination.

South Africa has a population with a high baseline level of Covid-19. During the recent surge in the omicron variant, the effectiveness of two doses of the BNT162b2 mRNA vaccine and the Ad26.COV2.S vaccine was assessed. Both vaccines provided a high level of protection against severe Covid-19.

The spread of the omicron variant produced an increase in Covid-19 in Israel in late 2021, and a second boost of BNT162b2 vaccine was authorized in early January 2022. This article reports the efficacy of the fourth dose among Israeli citizens 60 years of age or older. Rates of severe illness were reduced by a factor of 3.5 in the fourth week after the second boost.

In this study evaluating BNT162b2, vaccine effectiveness against hospitalization for Covid-19 in the delta-predominant period among adolescents 12 to 18 years of age was more than 90%; during the omicron period, vaccine effectiveness was 40% against hospitalization and 79% against critical illness. Vaccine effectiveness against hospitalization was 68% among children 5 to 11 years of age.

Multiple medications in common use have been considered for the treatment of Covid-19. In this double-blind, randomized, placebo-controlled trial, ivermectin that was administered within 7 days after Covid-19 symptom onset was shown not to be of any clinical benefit.

In this multicenter, double-blind trial of convalescent plasma for early, symptomatic SARS-CoV-2 infection, 1225 patients were randomly assigned to receive convalescent plasma or control plasma within 9 days after the onset of symptoms. Significantly fewer recipients of convalescent plasma had progression of Covid-19–associated illness leading to hospitalization.

Although considerable data show cross-reactivity among antibodies generated by infection with the various SARS-CoV-2 variants of interest, a group of persons who were not previously vaccinated but were recovering from infection with the omicron BA.1 variant were found to have antibodies that were largely ineffective in neutralizing the other viral strains.

Health care workers in Israel were given a fourth dose of BNT162b2 or mRNA-1273 vaccine during a period of omicron-variant predominance. Levels of antibodies to SARS-CoV-2 had waned 5 months after a third dose, and the fourth dose boosted antibodies to the maximum level observed after the third dose but no higher. Vaccine efficacy was 31 to 43% against symptomatic disease.

Although two doses of BNT162b2 vaccine produce immunity that wanes over time, the administration of a booster dose substantially increases the level of neutralizing antibodies against both the BA.1 and BA.2 variants.

In persons who had received the BNT162b2 vaccine in Qatar, the incidence of infection with the omicron variant after 35 days of observation was 2.4% among those who had received three doses and 4.5% among those who were vaccinated but not boosted; among those who had received the mRNA-1273 vaccine, the incidence was 1.0% with a boost and 1.9% without.

Among the first 100 patients who received sotrovimab, a monoclonal antibody directed against SARS-CoV-2, at a center in Australia, 8 had persistently positive SARS-CoV-2 polymerase-chain-reaction tests. Isolates obtained from 4 patients showed a mutation associated with resistance to sotrovimab in the receptor-binding domain, and cultures were positive at 2 to 3 weeks after treatment.

In this ongoing, randomized, phase 3 trial, sotrovimab (a SARS-CoV-2–targeted monoclonal antibody) or placebo was administered to outpatients within 5 days after the onset of Covid-19 symptoms. The incidence of hospitalization for any cause or death was lower among patients who received sotrovimab (1% vs. 7%).

In Gauteng, where the omicron variant was first identified, two thirds of unvaccinated residents were seropositive for SARS-CoV-2, which indicates past infection. Omicron peaked just 1 month after being detected; hospitalizations and deaths did not increase in proportion to cases. Whether this change is related to widespread preexisting immunity or to features of the virus is unclear.

The editors of the Journal note that although the rapid development of Covid-19 vaccines would appear to be a landmark success in global health mobilization, the truth is very different: the availability of the vaccines differs vastly across the globe.

Nirmatrelvir is an M^pro inhibitor active against SARS-CoV-2 and is given with ritonavir, a pharmacokinetic enhancer. In this double-blind, placebo-controlled trial, nirmatrelvir plus ritonavir, when given within 5 days after symptom onset to patients at high risk for disease progression, decreased the risk of Covid-19–related hospitalization or death by 87.8%.

In a retrospective cohort study from Israel, 149,032 patients who had recovered from SARS-CoV-2 infection were followed over a 270-day period to assess the rate of reinfection according to whether they had subsequently received a Covid-19 vaccine or had remained unvaccinated. The reinfection rate was 10.21 cases per 100,000 persons per day among unvaccinated patients and 2.46 cases among vaccinated patients.

Among more than 35,000 health care workers, those who received two doses of BNT162b2 vaccine had a high level of protection against Covid-19, regardless of the between-dose interval, but efficacy began to wane after 6 months. Immunity in vaccinated, previously infected persons was more effective and durable (>1 year) than that in vaccinated persons who had not been infected.

A 61-year-old man was evaluated after having jaundice, light-colored stools, dark urine, pruritus, fatigue, and a temperature of up to 39°C (without chills) for 1 week. He had dull pain in the right upper quadrant of the abdomen and had nausea but no vomiting. Six weeks before jaundice developed, he had been hospitalized with Covid-19. What is the diagnosis?

Omicron’s spread in South Africa has led to fewer hospitalizations and deaths per documented case than were seen during previous waves. But caution is warranted when it comes to making inferences about omicron’s intrinsic severity using population-level observations.

Neutralization of the omicron variant was assessed in serum samples obtained from persons who had received an mRNA-1273 booster. After the standard two-dose vaccine regimen, these titers were approximately 35 times lower than those against the D614G variant. However, boosters increased omicron neutralization by a factor of 20 — to levels that correlate with clinical resistance to infection.

The protection afforded by the mRNA-1273 vaccine against SARS-CoV-2 infection in Qatar seemed to wane over several months after vaccination; however, protection against serious infection, hospitalization, and death showed no evidence of decline over at least 6 months.

In a study involving recipients of the Chinese inactivated vaccines and the ZF2001 protein subunit vaccine, neutralizing antibody titers were higher when the interval between the second and third dose was 5 months rather than 1 month. Among the ZF2001 recipients in the prolonged-interval group, nearly 70% had neutralizing antibodies to the omicron variant 4 to 6 months after the third dose.

Serum from vaccinated persons was assayed for ability to neutralize the omicron variant of SARS-CoV-2. Persons who had received two doses of the BNT162b2, mRNA-1273, or ChAdOx1-S vaccine had serum that poorly neutralized omicron, but those who had recovered from infection and were then vaccinated or who had been vaccinated and had breakthrough infection had high levels of neutralizing activity.

Serum samples from 20 participants who had received two doses of the BNT162b2 vaccine and from 20 who had received three doses were assessed for ability to neutralize the omicron variant of SARS-CoV-2 in vitro. Neutralization activity was poor after two vaccine doses. However, substantial neutralization of the omicron variant was detected in samples from participants who had received three doses.

Neutralization assays of SARS-CoV-2 pseudoviruses expressing wild-type, omicron, or a synthetic resistant spike protein in plasma drawn from 47 people over time showed much lower omicron neutralization than Wuhan-hu-1 neutralization after two doses of an mRNA vaccine. However, samples from persons vaccinated after recovery from Covid-19 and those who received a booster vaccine had high levels of omicron neutralization.

In a trial of mRNA-1273 or placebo involving 3700 adolescents 12 to 17 years of age, two doses of vaccine stimulated high levels of neutralizing antibodies, with a side-effect profile similar to that seen in other age groups. The incidence of Covid-19 in the unvaccinated group was too low to gauge protection, but Covid-19 did not develop in any vaccinated participants.

In an active surveillance program from the Israeli Ministry of Health, estimates of myocarditis risk in the 21 days after a first and second dose of vaccine were, respectively, 0.56 per 100,000 and 8.09 per 100,000 among male recipients and 0 per 100,000 and 0.69 per 100,000 among female recipients.

This randomized trial of the BNT162b2 vaccine involved 2260 adolescents 12 to 15 years of age. Similar levels of antibody to SARS-CoV-2 were elicited in the 12-to-15-year-old participants and in 16-to-25-year-old participants in a parallel trial. Among participants with no evidence of previous infection, no cases of Covid-19 were diagnosed in vaccine recipients, as compared with 16 cases in placebo recipients.

In two matched retrospective cohort studies comparing BNT162b2 and mRNA-1273 Covid-19 vaccines (>190,000 recipients each), both were highly effective at preventing hospitalization and death. The incidence of breakthrough infections was lower among mRNA-1273–vaccinated persons (0.59%; 95% CI, 0.55 to 0.64) than among BNT162b2-vaccinated persons (0.84%; 95% CI, 0.79 to 0.89).

In this study, 37% of 146,000 PCR-tested contacts of infected persons in England were positive for SARS-CoV-2. Transmission of the alpha variant from twice-vaccinated index patients was rarer than that from unvaccinated index patients (adjusted rate ratio with BNT162b2, 0.32). Vaccine protection waned over time and was more effective against the alpha strain than against the delta strain.

Little is known regarding appropriate patient selection for and clinical outcomes with lung transplantation for respiratory failure due to Covid-19. This study analyzes lung transplantations reported in the United Network for Organ Sharing registry from August 2020 through September 2021.

In nursing homes, the lowest quartile of staff vaccination rates in counties in the highest quartile of prevalence of Covid-19 was associated with 1.56 additional cases per 100 beds among residents, 1.50 additional cases per 100 beds among staff, and 0.19 additional Covid-19–related deaths of residents per 100 beds relative to the highest quartile of staff vaccination rates in the same county.

The authors hypothesize that anti-idiotype immune responses may contribute to rare adverse events, such as myocarditis, after SARS-CoV-2 vaccination, as well as to sequelae of Covid-19 that persist after the resolution of infection.

Investigators used a case–control, test-negative design to assess the effectiveness of the BNT162b2 vaccine in adolescents for the prevention of Covid-19–related hospitalization, ICU admission, or receipt of life support. Among 445 case patients and 777 controls, of the 180 patients admitted to an ICU, only 2 had been fully vaccinated; all 7 deaths occurred in unvaccinated patients.

In an analysis involving more than 10 million North Carolina residents, Covid-19 vaccines were highly effective in preventing hospitalization and death up to 9 months after vaccination. Waning protection against infection over time was due to both declining immunity and the emergence of the delta variant.

During a surge in cases of Covid-19 in Israel, a rapid deployment of BNT162b2 booster injections was initiated in long-term care facilities over a 3-week period in July. When infection rates were increasing in the general population, rates in long-term care facilities decreased by 71%, and hospitalization rates fell by 80%.

Among 843,208 participants in Israel who were 50 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, those who received a booster had 90% lower mortality due to Covid-19 than those who did not receive a booster. The study period was 54 days; adverse effects were not recorded.

In a study involving 4.7 million fully vaccinated persons in Israel, the rate of confirmed Covid-19 was lower among those who received a booster than among those who did not by a factor of approximately 10. Among participants 60 years of age or older, the rate of severe illness was lower by a factor of 17.9 and the rate of death by a factor of 14.7.

NVX-CoV2373 is a vaccine containing a full-length stabilized recombinant spike protein trimer that is administered in two doses 3 weeks apart along with a saponin-based adjuvant. In a randomized trial, approximately 20,000 participants received the vaccine and 10,000 a placebo. Vaccine efficacy against infection was 90%, and reactogenicity was similar to that of other Covid-19 vaccines.