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1.
J Infect Chemother ; 28(7): 907-911, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1828881

ABSTRACT

BACKGROUND: Little research has been done on post-exposure prophylaxis (PEP) for COVID-19. This study was done to determine if maoto, a traditional herbal medicine commonly used for diseases with symptoms similar to those of COVID-19, can be repurposed for post-exposure prophylaxis to prevent the spread of nosocomial infection with SARS-CoV-2. METHODS: A cohort analysis was done of the data of 55 health care workers (HCWs) whether to get infected with SARS-CoV-2 in a Japanese hospital experiencing a COVID-19 cluster in April of 2021. Of these subjects, maoto granules for medical use were prescribed for PEP to 42 HCWs and taken for three days in mid-April. Controls were 13 HCWs who rejected the use of maoto. Polymerase chain reaction was performed routinely once or twice a week or when a participant presented with symptoms of COVID-19. RESULT: There were no background differences between the maoto and control groups by profession, sex, or mean age. No severe adverse reactions were observed. During the observation period of 1 week, significantly fewer subjects were diagnosed with COVID-19 in the maoto group (N = 3, 7.1%) than in the control group (N = 6, 46.2%). The prophylactic effectiveness of maoto was 84.5%. CONCLUSION: Oral administration of maoto is suggested to be effective as PEP against nosocomial COVID-19 infection.


Subject(s)
COVID-19 , COVID-19/drug therapy , COVID-19/prevention & control , Health Personnel , Herbal Medicine , Humans , Japan , Post-Exposure Prophylaxis , SARS-CoV-2
2.
Front Public Health ; 10: 769898, 2022.
Article in English | MEDLINE | ID: covidwho-1775977

ABSTRACT

Background: In Africa, rabies causes an estimated 24,000 human deaths annually. Mass dog vaccinations coupled with timely post-exposure prophylaxis (PEP) for dog-bite patients are the main interventions to eliminate human rabies deaths. A well-informed healthcare workforce and the availability and accessibility of rabies biologicals at health facilities are critical in reducing rabies deaths. We assessed awareness and knowledge regarding rabies and the management of rabies among healthcare workers, and PEP availability in rural eastern Kenya. Methodology: We interviewed 73 healthcare workers from 42 healthcare units in 13 wards in Makueni and Kibwezi West sub-counties, Makueni County, Kenya in November 2018. Data on demographics, years of work experience, knowledge of rabies, management of bite and rabies patients, and availability of rabies biologicals were collected and analyzed. Results: Rabies PEP vaccines were available in only 5 (12%) of 42 health facilities. None of the health facilities had rabies immunoglobulins in stock at the time of the study. PEP was primarily administered intramuscularly, with only 11% (n = 8) of the healthcare workers and 17% (7/42) healthcare facilities aware of the dose-sparing intradermal route. Less than a quarter of the healthcare workers were aware of the World Health Organization categorization of bite wounds that guides the use of PEP. Eighteen percent (n = 13) of healthcare workers reported they would administer PEP for category I exposures even though PEP is not recommended for this category of exposure. Only one of six respondents with acute encephalitis consultation considered rabies as a differential diagnosis highlighting the low index of suspicion for rabies. Conclusion: The availability and use of PEP for rabies was sub-optimal. We identified two urgent needs to support rabies elimination programmes: improving availability and access to PEP; and targeted training of the healthcare workers to improve awareness on bite wound management, judicious use of PEP including appropriate risk assessment following bites and the use of the dose-sparing intradermal route in facilities seeing multiple bite patients. Global and domestic funding plan that address these gaps in the human health sector is needed for efficient rabies elimination in Africa.


Subject(s)
Disease Eradication , Health Services Needs and Demand , Rabies , Rural Health , Animals , Bites and Stings/therapy , Disease Eradication/methods , Disease Eradication/organization & administration , Dog Diseases/prevention & control , Dog Diseases/virology , Dogs , Health Knowledge, Attitudes, Practice , Health Personnel/psychology , Humans , Kenya/epidemiology , Mass Vaccination/veterinary , Post-Exposure Prophylaxis/supply & distribution , Rabies/epidemiology , Rabies/prevention & control , Rabies/veterinary , Rabies Vaccines/supply & distribution
3.
MEDICC Rev ; 24(1): 70-75, 2022 Jan 31.
Article in English | MEDLINE | ID: covidwho-1687931

ABSTRACT

We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus' entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Child, Preschool , Cuba , Humans , Immunity, Innate , Post-Exposure Prophylaxis , Secondary Prevention
4.
Vestn Otorinolaringol ; 86(6): 69-73, 2021.
Article in Russian | MEDLINE | ID: covidwho-1599955

ABSTRACT

OBJECTIVE: To evaluate the therapeutic and preventive efficacy of the drug with antiviral and immunotropic activity Cytovir-3 in children with COVID-19 on an outpatient basis. MATERIAL AND METHODS: A retrospective analysis the treatment of 52 pediatric patients aged 1 to 17 years with a confirmed new coronavirus infection SARS-CoV-2 with the drug Cytovir-3 was carried out. 28 people, contacts in the family, received the drug for prophylactic purposes. Clinical observation of patients was carried out with an assessment of the severity and duration of fever, the anosmia, catarrhal symptoms in the nasopharynx and analysis indicator of saturation. In the control group, there were 27 patients of the same age who received the medicine Umifenovir and 25 contact family members who did not receive the medicine for prophylactic purposes. RESULTS: The use of Cytovir-3 in the COVID-19 treatment in children led to a decrease in intoxication symptoms 3.2-3.4 days after taking the medicine, a significant reduction of anosmia period recovery time, and elimination of the pathogen according to PCR analysis. The patients receiving the drug did not have ENT- complications and did not require hospitalization. Prophylactic administration of the drug in contact family members statistically significantly reduced the likelihood of developing the disease 3.6 times. The clinical efficacy and feasibility of using Cytovir-3 in the treatment and prevention of new coronavirus infection in patients of different ages has been shown.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 , Adolescent , COVID-19/drug therapy , COVID-19/prevention & control , Child , Child, Preschool , Humans , Infant , Outpatients , Post-Exposure Prophylaxis , Retrospective Studies
6.
Eur J Haematol ; 108(2): 91-98, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1488195

ABSTRACT

People with hematologic malignancies are at a high risk of morbidity and mortality from COVID-19. The response to vaccination is highly limited in patients with chronic lymphocytic leukemia. Less than half of the patients develop antibody response, suggesting that they remain at risk of SARS-CoV-2 infection even after the vaccination. Reasons for inadequate response to COVID-19 vaccination in chronic lymphocytic leukemia are multifactorial and attributed to disease-related immune dysregulation and patient- and therapy-related factors. The negative predictors of response to vaccination include hypogammaglobulinemia, advanced age, current active treatment, and past treatment anti-CD20 monoclonal antibodies. Despite using booster doses and heterologous immunization to improve humoral and cellular immunity, some patients with chronic lymphocytic leukemia will fail to respond. Active treatment at the time of vaccination and a recent history of anti-CD20 monoclonal antibodies use are the strongest predictors of the non-response. Current data support informing patients with chronic lymphocytic leukemia and other hematologic malignancies about the risk of infection regardless of vaccination. These individuals and members of their households should continue extreme preventive actions despite relaxed local regulations. Other emerging non-vaccine preventive strategies include passive and post-exposure prevention with monoclonal antibodies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , SARS-CoV-2/immunology , COVID-19 Vaccines/administration & dosage , Hematologic Neoplasms/complications , Hematologic Neoplasms/immunology , Humans , Immunization, Passive/methods , Immunocompromised Host , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pandemics , Post-Exposure Prophylaxis/methods , Risk Factors , Treatment Failure
7.
Trials ; 22(1): 726, 2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1477453

ABSTRACT

The efficient community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the current pandemic of coronavirus disease-2019 (COVID-19), which in severe and critical cases results in progressive pulmonary infection, complicated by respiratory failure, with a high prevalence of acute respiratory distress syndrome. Of all age groups, older adults have the greatest risk of severe COVID-19 and the associated complications. Globally, there are many reports of the rapid spread of COVID-19 among residents of skilled nursing facilities, with high associated rates of morbidity and mortality. With over 1.3 million residents in nursing home care in the USA, there is an urgent need for therapeutic strategies to prevent COVID-19 in these populations.Lilly, in collaboration with the National Institute of Allergy and Infectious Diseases, conducted the BLAZE-2 trial to evaluate the efficacy and safety of the monoclonal antibody bamlanivimab (LY3819253) in preventing SARS-CoV-2 infection and COVID-19, defined as symptomatic infection, in skilled nursing and assisted living facilities. It is a phase 3 randomized, double-blind, placebo-controlled trial, where participants were randomized to bamlanivimab (4200 mg) or placebo and then followed up for 24 weeks. Conducting a trial in the midst of a pandemic in these facilities poses several challenges, including a vulnerable elderly population, travel restrictions, supply chain interruptions, and defining the target population. The operational challenges were addressed by the innovative use of mobile research units which are customized, equipped, and staffed to support BLAZE-2 randomization and participant dosing within the skilled nursing and assisted living facilities. Herein, we describe the design of the study, the analytics behind facility selection, and an innovative operational model.


Subject(s)
Assisted Living Facilities , COVID-19 , Aged , Clinical Trials as Topic , Humans , Post-Exposure Prophylaxis , SARS-CoV-2
8.
Am J Nurs ; 121(11): 22, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1475853

ABSTRACT

The emergency use authorization for REGEN-COV (a combination of two monoclonal antibodies, casirivimab and imdevimab) has been revised to include postexposure prophylaxis of COVID-19 in adults and children 12 years of age and older who, if they become COVID-19 positive, are at high risk for severe disease.Prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/prevention & control , Drug Approval , Post-Exposure Prophylaxis , Adolescent , Adult , Aged , Child , Drug Combinations , Humans , Middle Aged , United States , Young Adult
9.
Int J Environ Res Public Health ; 18(20)2021 10 14.
Article in English | MEDLINE | ID: covidwho-1470849

ABSTRACT

Australia introduced a national lockdown on 22 March 2020 in response to the COVID-19 pandemic. Melbourne, but not Sydney, had a second COVID-19 lockdown between July and October 2020. We compared the number of HIV post-exposure prophylaxis (PEP) prescriptions, HIV tests, and new HIV diagnoses during these lockdown periods. The three outcomes in 2020 were compared to 2019 using incidence rate ratio. There was a 37% and 46% reduction in PEP prescriptions in Melbourne and Sydney, respectively, with a larger reduction during lockdown (68% and 57% reductions in Melbourne's first and second lockdown, 60% reduction in Sydney's lockdown). There was a 41% and 32% reduction in HIV tests in Melbourne and Sydney, respectively, with a larger reduction during lockdown (57% and 61% reductions in Melbourne's first and second lockdowns, 58% reduction in Sydney's lockdown). There was a 44% and 47% reduction in new HIV diagnoses in Melbourne and Sydney, respectively, but no significant reductions during lockdown. The reduction in PEP prescriptions, HIV tests, and new HIV diagnoses during the lockdown periods could be due to the reduction in the number of sexual partners during that period. It could also result in more HIV transmission due to substantial reductions in HIV prevention measures during COVID-19 lockdowns.


Subject(s)
COVID-19 , HIV Infections , Australia/epidemiology , Cities , Communicable Disease Control , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Pandemics , Post-Exposure Prophylaxis , SARS-CoV-2
11.
Am J Trop Med Hyg ; 105(4): 986-990, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1359352

ABSTRACT

Travelers are a risk-group for rabies; however, few are protected. We describe changes in pre-travel vaccination rates and post-travel referrals after animal contact. We conducted a nationwide, retrospective study for 2014-2018. The ratio of rabies vaccine courses distributed to travelers and the number of Israeli-tourist-entries to endemic countries was calculated, as was the proportion of travelers referred to a post-travel clinic after animal contact. During the study period, the ratio of pre-travel vaccine courses distributed nationally to outgoing tourism to endemic countries was stable at ≈0.7%; 13% of 256,969 pre-travel consultations included recommendation for rabies vaccination. Backpackers were more likely to be immunized (40.2%) than business travelers (4.4%) or travelers planning organized/high-end travel (2.0%). However, rates of rabies vaccination among backpackers showed a decline during the study period. Post-travel referrals after animal contact were stable at 2% of all referrals; most were exposed in Asia (69.5%) and 51% were bitten by dogs. Only 38% received post-exposure prophylaxis abroad. We conclude that only a minority of Israeli travelers, including backpackers, receive rabies pre-exposure prophylaxis. The proportion of travelers with potentially rabid animal contact is not decreasing; however, many exposed travelers do not receive post-exposure prophylaxis during travel. Because rabies control programs have been compromised in endemic countries during the COVID-19 pandemic, the need to provide rabies protection to travelers has become more urgent. After the ACIP's adoption of the World Health Organization's (WHO) 2-dose regimen, a revision of current vaccine guidelines is required to provide a simplified, more inclusive rabies vaccine policy.


Subject(s)
Rabies Vaccines/administration & dosage , Rabies/prevention & control , Travel , Vaccination/trends , Adolescent , Adult , Female , Humans , Israel , Male , Middle Aged , Post-Exposure Prophylaxis , Pre-Exposure Prophylaxis , Referral and Consultation/statistics & numerical data , Retrospective Studies , Travel-Related Illness , Young Adult
13.
Cochrane Database Syst Rev ; 7: CD015017, 2021 07 28.
Article in English | MEDLINE | ID: covidwho-1328590

ABSTRACT

BACKGROUND: Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting. OBJECTIVES: To assess the efficacy and safety of ivermectin compared to no treatment, standard of care, placebo, or any other proven intervention for people with COVID-19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS-CoV-2 (postexposure prophylaxis). SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), medRxiv, and Research Square, identifying completed and ongoing studies without language restrictions to 26 May 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing ivermectin to no treatment, standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity, treated in inpatient or outpatient settings, and for prevention of SARS-CoV-2 infection. Co-interventions had to be the same in both study arms.  We excluded studies comparing ivermectin to other pharmacological interventions with unproven efficacy. DATA COLLECTION AND ANALYSIS: We assessed RCTs for bias, using the Cochrane risk of bias 2 tool. The primary analysis excluded studies with high risk of bias. We used GRADE to rate the certainty of evidence for the following outcomes 1. to treat inpatients with moderate-to-severe COVID-19: mortality, clinical worsening or improvement, adverse events, quality of life, duration of hospitalization, and viral clearance; 2. to treat outpatients with mild COVID-19: mortality, clinical worsening or improvement, admission to hospital, adverse events, quality of life, and viral clearance; (3) to prevent SARS-CoV-2 infection: SARS-CoV-2 infection, development of COVID-19 symptoms, adverse events, mortality, admission to hospital, and quality of life. MAIN RESULTS: We found 14 studies with 1678 participants investigating ivermectin compared to no treatment, placebo, or standard of care. No study compared ivermectin to an intervention with proven efficacy. There were nine studies treating participants with moderate COVID-19 in inpatient settings and four treating mild COVID-19 cases in outpatient settings. One study investigated ivermectin for prevention of SARS-CoV-2 infection. Eight studies had an open-label design, six were double-blind and placebo-controlled. Of the 41 study results contributed by included studies, about one third were at overall high risk of bias.  Ivermectin doses and treatment duration varied among included studies.  We identified 31 ongoing and 18 studies awaiting classification until publication of results or clarification of inconsistencies. Ivermectin compared to placebo or standard of care for inpatient COVID-19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 2 studies, 185 participants; very low-certainty evidence) and clinical worsening up to day 28 assessed as need for invasive mechanical ventilation (IMV) (RR 0.55, 95% CI 0.11 to 2.59; 2 studies, 185 participants; very low-certainty evidence) or need for supplemental oxygen (0 participants required supplemental oxygen; 1 study, 45 participants; very low-certainty evidence), adverse events within 28 days (RR 1.21, 95% CI 0.50 to 2.97; 1 study, 152 participants; very low-certainty evidence), and viral clearance at day seven (RR 1.82, 95% CI 0.51 to 6.48; 2 studies, 159 participants; very low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on clinical improvement up to 28 days (RR 1.03, 95% CI 0.78 to 1.35; 1 study; 73 participants; low-certainty evidence) and duration of hospitalization (mean difference (MD) -0.10 days, 95% CI -2.43 to 2.23; 1 study; 45 participants; low-certainty evidence). No study reported quality of life up to 28 days. Ivermectin compared to placebo or standard of care for outpatient COVID-19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality up to 28 days (RR 0.33, 95% CI 0.01 to 8.05; 2 studies, 422 participants; very low-certainty evidence) and clinical worsening up to 14 days assessed as need for IMV (RR 2.97, 95% CI 0.12 to 72.47; 1 study, 398 participants; very low-certainty evidence) or non-IMV or high flow oxygen requirement (0 participants required non-IMV or high flow; 1 study, 398 participants; very low-certainty evidence). We are uncertain whether ivermectin compared to placebo reduces or increases viral clearance at seven days (RR 3.00, 95% CI 0.13 to 67.06; 1 study, 24 participants; low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on the number of participants with symptoms resolved up to 14 days (RR 1.04, 95% CI 0.89 to 1.21; 1 study, 398 participants; low-certainty evidence) and adverse events within 28 days (RR 0.95, 95% CI 0.86 to 1.05; 2 studies, 422 participants; low-certainty evidence). None of the studies reporting duration of symptoms were eligible for primary analysis. No study reported hospital admission or quality of life up to 14 days. Ivermectin compared to no treatment for prevention of SARS-CoV-2 infection We found one study. Mortality up to 28 days was the only outcome eligible for primary analysis. We are uncertain whether ivermectin reduces or increases mortality compared to no treatment (0 participants died; 1 study, 304 participants; very low-certainty evidence). The study reported results for development of COVID-19 symptoms and adverse events up to 14 days that were included in a secondary analysis due to high risk of bias. No study reported SARS-CoV-2 infection, hospital admission, and quality of life up to 14 days. AUTHORS' CONCLUSIONS: Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.


Subject(s)
Antiparasitic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Ivermectin/therapeutic use , Antiparasitic Agents/adverse effects , Antiviral Agents/adverse effects , COVID-19/mortality , COVID-19/prevention & control , COVID-19/virology , Cause of Death , Humans , Ivermectin/adverse effects , Placebos/therapeutic use , Post-Exposure Prophylaxis , Randomized Controlled Trials as Topic , Respiration, Artificial/statistics & numerical data , SARS-CoV-2/drug effects , Time Factors , Treatment Outcome
14.
Viruses ; 13(7)2021 07 02.
Article in English | MEDLINE | ID: covidwho-1295938

ABSTRACT

The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus Disease 2019 (COVID-19), which can vary in severity, from asymptomatic or mild disease (the vast majority of the cases) to respiratory failure, multi-organ failure, and death. Recently, several vaccines were approved for emergency use against SARS-CoV-2. However, their worldwide availability is acutely limited, and therefore, SARS-CoV-2 is still expected to cause significant morbidity and mortality in the upcoming year. Hence, additional countermeasures are needed, particularly pharmaceutical drugs that are widely accessible, safe, scalable, and affordable. In this comprehensive review, we target the prophylactic arena, focusing on small-molecule candidates. In order to consolidate a potential list of such medications, which were categorized as either antivirals, repurposed drugs, or miscellaneous, a thorough screening for relevant clinical trials was conducted. A brief molecular and/or clinical background is provided for each potential drug, rationalizing its prophylactic use as an antiviral or inflammatory modulator. Drug safety profiles are discussed, and current medical indications and research status regarding their relevance to COVID-19 are shortly reviewed. In the near future, a significant body of information regarding the effectiveness of drugs being clinically studied for COVID-19 is expected to accumulate, in addition to information regarding the efficacy of prophylactic treatments.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Animals , COVID-19/epidemiology , COVID-19/immunology , Disease Outbreaks , Humans , Immunity, Innate , Pandemics , Post-Exposure Prophylaxis , Pre-Exposure Prophylaxis , SARS-CoV-2/isolation & purification
15.
Nature ; 596(7870): 103-108, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275940

ABSTRACT

Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21-3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many-but not all-of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/pharmacology , Antibodies, Viral/therapeutic use , COVID-19/virology , Neutralization Tests , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , COVID-19/genetics , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Female , Humans , Male , Mesocricetus/immunology , Mesocricetus/virology , Mice , Mice, Transgenic , Post-Exposure Prophylaxis , Pre-Exposure Prophylaxis , SARS-CoV-2/genetics , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
16.
Epidemiol Infect ; 149: e114, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-1209457

ABSTRACT

In November 2017, eight confirmed measles cases were reported to Public Health England from a hospital in the West Midlands. A multidisciplinary Incident Management Team (IMT) was established to determine the extent of the problem and coordinate an outbreak response. Between 1 November 2017 and 4 June 2018, a total of 116 confirmed and 21 likely measles cases were linked to this outbreak; just under half (43%) were aged over 15 years of age. Fifty-five of the confirmed cases were hospitalised (48%) and no deaths were reported. At the start of the outbreak, cases were mostly individuals of Romanian origin; the outbreak subsequently spread to the wider population. Over the 8-month response, the IMT conducted the following control measures: extensive contact tracing, immediate provision of post-exposure prophylaxis, community engagement amongst specific high-risk groups, MMR awareness raising including catch-up campaigns and enhanced vaccination services at selected GP surgeries. Key challenges to the effective control measures included language difficulties limiting community engagement; delays in diagnosis, notification and appropriate isolation of cases; limited resources for contact tracing across multiple high-risk settings (including GPs and hospitals) and lack of timely data on vaccine coverage in sub-groups of the population to guide public health action.


Subject(s)
Disease Outbreaks/prevention & control , Measles/epidemiology , Measles/prevention & control , Adolescent , Adult , Child , Child, Preschool , Contact Tracing , England/epidemiology , Female , Health Communication , Humans , Immunization Programs , Infant , Male , Measles/transmission , Measles virus , Measles-Mumps-Rubella Vaccine/administration & dosage , Post-Exposure Prophylaxis , Young Adult
17.
J Med Virol ; 93(9): 5358-5366, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1206839

ABSTRACT

Currently available data are consistent with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at temperatures encountered in the upper airways (25-33°C when breathing room temperature air, 25°C) compared to those in the lower airways (37°C). One factor that may contribute to more rapid viral growth in the upper airways is the exponential increase in SARS-CoV-2 stability that occurs with reductions in temperature, as measured in vitro. Because SARS-CoV-2 frequently initiates infection in the upper airways before spreading through the body, increased upper airway viral growth early in the disease course may result in more rapid progression of disease and potentially contribute to more severe outcomes. Similarly, higher SARS-CoV-2 viral titer in the upper airways likely supports more efficient transmission. Conversely, the possible significance of air temperature to upper airway viral growth suggests that prolonged delivery of heated air might represent a preventative measure and prophylactic treatment for coronavirus disease 2019.


Subject(s)
COVID-19/transmission , Nasopharynx/virology , SARS-CoV-2/physiology , Temperature , Trachea/virology , Virus Replication/physiology , Air/analysis , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Humans , Humidity , Post-Exposure Prophylaxis/methods , SARS-CoV-2/pathogenicity , Severity of Illness Index , Thermodynamics
18.
Ann Intern Med ; 174(3): 344-352, 2021 03.
Article in English | MEDLINE | ID: covidwho-1190610

ABSTRACT

BACKGROUND: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING: National U.S. multicenter study. PARTICIPANTS: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026). LIMITATION: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Hydroxychloroquine/therapeutic use , Post-Exposure Prophylaxis , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Double-Blind Method , Female , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , SARS-CoV-2 , Time Factors , Treatment Outcome , United States , Young Adult
19.
PLoS One ; 16(4): e0249036, 2021.
Article in English | MEDLINE | ID: covidwho-1172876

ABSTRACT

BACKGROUND: Hydroxychloroquine is not efficacious as post-exposure prophylaxis against coronavirus disease 2019 (COVID-19). It is not known whether as pre-exposure prophylaxis it may prevent COVID-19. OBJECTIVE: To compare the incidence of COVID-19 in Spanish patients with autoimmune rheumatic diseases treated with and without hydroxychloroquine. PATIENTS AND METHODS: Retrospective electronic record review, from February 27th to June 21st, 2020, of patients with autoimmune inflammatory diseases followed at two academic tertiary care hospitals in Seville, Spain. The cumulative incidence of confirmed COVID-19, by PCR or serology, was compared between patients with and without hydroxychloroquine as part of their treatment of autoimmune inflammatory diseases. RESULTS: Among 722 included patients, 290 (40%) were receiving hydroxychloroquine. During the seventeen-week study period, 10 (3.4% [95% CI: 1.7%-6.7%] cases of COVID-19 were registered among patients with hydroxychloroquine and 13 (3.0% [1.6%-5.1%]) (p = 0.565) in those without hydroxychloroquine. COVID-19 was diagnosed by PCR in four (1.4%, 95% CI 0.38%-3.5%) subject with hydroxychloroquine and six (1.4%, 95% CI 0.5%-3.0%) without hydroxychloroquine (p = 0.697). Three patients on hydroxychloroquine and four patients without hydroxychloroquine were admitted to the hospital, none of them required to be transferred to the intensive care unit and no patient died during the episode. CONCLUSIONS: The incidence and severity of COVID-19 among patients with autoimmune rheumatic diseases with and without hydroxychloroquine was not significantly different.


Subject(s)
COVID-19 , Hydroxychloroquine/administration & dosage , Post-Exposure Prophylaxis , Pre-Exposure Prophylaxis , Rheumatic Diseases/drug therapy , SARS-CoV-2 , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Rheumatic Diseases/epidemiology , Risk Factors , Spain/epidemiology
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