The Manual is compiling some of the most significant news items regarding COVID-19 to help people stay up to date.
July 30, 2020
Rapid decay of anti-SARS-CoV-2 antibodies
In a correspondence published in The New England Journal of Medicine, researchers from the David Geffen School of Medicine at the University of California reported on a small study done on 31 participants who recovered from mild COVID-19 and had their antibody levels to the SARS CoV-2 virus quantified. Measurements showed a rapid decay of anti-SARS-CoV-2 antibodies. The authors noted that a recent study had suggested a rapid decay of these antibodies but the rate was not described in detail. In the current study, the first antibody level was obtained at 37 days after the onset of symptoms (range, 18 to 65) and last measurement was obtained 86 days after the onset of symptoms (range, 44 to 119). The mean decrease in the level of antibodies suggested a half-life of approximately 36 days over the observation period. The authors concluded that the early antibody decay after acute viral exposures raises the concern that humoral immunity against SARS-CoV-2 may not be long-lasting in persons with mild illness. They raised concerns regarding antibody-based immunity passports, herd immunity, and perhaps vaccine durability in light of their findings and what is already known about common human coronaviruses.
July 29, 2020
FDA warns consumers and health care professionals not to use certain alcohol-based hand sanitizers
In a press release, July 27, 2020, the US Food and Drug Administration (FDA) reiterated its warning not to use certain hand sanitizers containing methanol. There have been an increasing number of adverse events including blindness, cardiac effects, effects on the central nervous system, and hospitalizations and deaths. The news release also reported the FDA's latest enforcement efforts to prevent certain hand sanitizers from entering the country. The FDA stresses that consumers must be vigilant about which hand sanitizers they use and urges consumers to immediately stop using all hand sanitizers on the FDA's list of dangerous hand sanitizer products. Methanol, commonly known as wood alcohol, is a dangerous substance. Exposure can result in nausea, vomiting, headache, blurred vision, permanent blindness, seizures, coma, permanent damage to the nervous system, or death. People using these products on their hands are at risk for methanol poisoning; however, young children who ingest these products or adolescents and adults who drink these products as an alcohol substitute are at most risk.
July 23, 2020
Making the case for aerosol transmission of SARS-CoV-2
Making the case that SARS-CoV-2 can be transmitted by aerosols, Kimberly Prather, Chair of Atmospheric Chemistry at the Scripps Institute of Oceanography, University of California San Diego, and colleagues authored an article published in Science that explained the science and reasoning why aerosol transmission can and does occur. Dr. Prather notes that, given how little is known about the production and airborne behavior of infectious respiratory droplets, it is difficult to define a safe distance for social distancing. She states that assuming the SARS-CoV-2 virions (the complete, infective form of a virus) are contained in submicron aerosols, as is the case for influenza viruses, a good comparison is exhaled cigarette smoke, which also contains submicron particles and will likely follow comparable flows and dilution patterns. “The distance from a smoker at which one smells cigarette smoke indicates the distance in those surroundings at which one could inhale infectious aerosols.” She believes masks are effective and that it is important to wear a properly fitted mask indoors even when 6 feet apart.
July 20, 2020
Transmission of SARS-CoV-2: A brief by the World Health Organization
The World Health Organization published a scientific brief, July 9, 2020, updating the current knowledge concerning COVID-19 transmission. The brief was undertaken by World Health Organization and their partners to consolidate information from reviews and publications in peer-reviewed journals and non peer-reviewed manuscripts in preprint servers. The document discusses the different modes in which the virus may be transmitted and when people infected with SARS-CoV-2 can infect others. The brief also explores the question of whether asymptomatic or pre-symptomatic transmission occurs. The World Health Organization brief underscores that understanding how the infection is spread, and when and in which settings the virus is transmitted, have important implications for strategies in preventing the disease.
July 17, 2020
Maternal-fetal transmission of SARS-CoV-2 infection
Some cases of transmission of SARS-CoV-2 infection to a newborn have been described, but it is unclear whether the infection was transmitted before or during birth or was caused by environmental exposure after birth. In the July 14, 2020, issue of Nature Communications, researchers shared a report of a newborn becoming infected with the SARS-CoV-2 virus through the placenta. Doctors examined the placenta and confirmed that the tissue contained high levels of the SARS-CoV-2 virus. The newborn had symptoms of brain injury that were similar to those of older patients with COVID-19.
July 15, 2020
Italian study finds 81.9% of individuals aged 20 years or younger have no symptoms following infection with the coronavirus
Age-specific estimates on the probability of developing symptoms upon infection with SARS-CoV-2 are sparse. Strategies for controlling the spread of the infection that rely on testing close contacts of individuals with the infection and isolating those who test positive are hampered by asymptomatic infections, which are easily missed by surveillance teams. Of particular relevance is transmission of infection by children given they are much less likely to experience symptoms. In a study done in Lombardy, Italy, clinical observations were made of the close contacts of 64,252 people with laboratory-confirmed SARS-CoV-2 infection. In the study, a cluster of 3,420 infected individuals were identified where all close contacts were tested for COVID-19 either by nasal swabs or serological testing, yielding overall sample size of 5,484 close contacts. Among the selected 5,484 close contacts, 51.5% or 2,824 tested positive. Of the 2,824 confirmed SARS-CoV-2 infections, 876 or 31% were symptomatic. Symptomatic cases were defined as showing upper or lower respiratory tract symptoms (eg, cough, shortness of breath) or fever ≥ 37.5 °C. The data were stratified by age, and researchers found that the probability of developing symptoms increased with age:
- Age < 20 years: 18.1% developed symptoms
- Age 20–39 years: 22.4% developed symptoms
- Age 40–59 years: 30.5% developed symptoms
- Age 60–79 years: 35.5% developed symptoms
- Age > 80 years: 64.6% developed symptoms
The authors noted that the contribution of asymptomatic infections to transmission of SARS-CoV-2 is poorly quantified and the estimates of the proportion of SARS-CoV-2 infections which are asymptomatic range from 17 to 87%, depending on what symptoms were included in the definition and when they were ascertained. This study shows that the likelihood of experiencing symptoms of SARS-Cov-2 infection increases with age. This study represents a useful piece of information that may lead us to better understand the role of children and young adults in the epidemiology of COVID-19. This preliminary study does not yet appear in a peer-reviewed journal, but its authors have made their findings available online, on the preprint platform arXiv.
July 14, 2020
A large proportion of COVID-19 patients had persistent symptoms after recovery from acute infection
A study done by Italian researchers and published in in the Journal of the American Medical Association found that a large number of COVID-19 patients had lingering symptoms. The study included 143 patients who were discharged from the hospital after recovery from COVID-19. All patients had met criteria for discontinuation of quarantine (no fever for 3 consecutive days, improvement in other symptoms, and 2 negative tests results for COVID-19, 24 hours apart). Patients enrolled in the study an average 36 days after discharge and had another negative PCR test for COVID-19 at the time of enrollment. The majority of patients reported fatigue and shortness of breath as persisting symptoms. At the time of evaluation, only 12.6% were completely free of any COVID-19 related symptoms, while 30% had one or two symptoms, and 55% had three or more symptoms. None the patients had a fever or any signs of acute illness. Worse quality-of-life was observed among 44.1% patients. A high proportion of individuals reported fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%), and chest pain (21.7%). The researchers point out that while much attention has been focused on the acute phase of COVID-19, continued monitoring after discharge for long-lasting effects is needed. The authors note that the study has limitations, including being a single-center study, and information about symptoms the patient had prior to the infection were not available. Furthermore, there was no control group for comparison.
July 2, 2020
CDC says pregnant women at greater risk for severe COVID-19
According to a new report published online in the Morbidity and Mortality Weekly Report (MMWR) on June 26, 2020, pregnant women may be at increased risk for severe COVID-19 illness. In women of reproductive age (15 to 44 years) who were infected with SARS-CoV-2 (the virus that causes COVID-19), pregnancy was associated with a greater likelihood of hospitalization, admission to the intensive care unit, and needing mechanical ventilation. However, pregnancy was not associated with increased risk of death. There were 8207 cases of pregnant women who tested positive for COVID-19 reported to the CDC as of June 7. These women were compared with the 83,205 women of reproductive age who were known not to be pregnant and who tested positive for COVID-19. There was a substantially greater proportion of hospital admissions among pregnant women (31.5%) compared with non-pregnant women (5.8%). ICU admissions were reported for 1.5% of pregnant women compared with 0.9% of their non-pregnant counterparts, and mechanical ventilation was required for 0.5% of pregnant women compared with 0.3% of their non-pregnant counterparts. Hispanic and African-American women appear more likely to be infected by SARS-CoV-2 during pregnancy. The authors point out that during pregnancy women experience physiologic and immunologic changes that could increase the risk for more severe illness resulting from respiratory infections. Although the study has several limitations, the authors of this CDC report state that “…pregnant women should be made aware of their potential risk for severe illness from COVID-19. Pregnant women and their families should take measures to ensure their health and prevent the spread of SARS-CoV-2 infection. Specific actions pregnant women can take include not skipping prenatal care appointments, limiting interactions with other people as much as possible, taking precautions to prevent getting COVID-19 when interacting with others, having at least a 30-day supply of medicines, and talking to their health care provider about how to stay healthy during the COVID-19 pandemic. To reduce severe outcomes from COVID-19 among pregnant women, measures to prevent SARS-CoV-2 infection should be emphasized, and potential barriers to the ability to adhere to these measures need to be addressed.”
June 29, 2020
The reduction in daily CO2 emissions during the COVID-19 confinement
The amount of carbon dioxide (CO2) being released by human activity each day fell as much as 17% during the height of the coronavirus crisis in early April according to a study published on May 17, 2020 in the journal Nature Climate Change. Government policies of confinement (quarantine or stay at home) to reduce transmission of the virus during the COVID-19 pandemic have drastically altered patterns of energy demand around the world. Daily emissions temporarily fell to levels last seen in 2006. The analysis was carried out by an international team of researchers working on a future Earth's global carbon project, an initiative to trace the impacts of human-generated greenhouse gases on the planet. The 17% decline in CO2 emissions came in early April when confinement measures around the world were at the peak. The overall impact on 2020 annual emissions depends on the duration of the confinement with a low estimate of a decrease of about 4% if pre-pandemic conditions return by June and high estimate of a decrease of about 7% if some restrictions remain worldwide until the end the 2020. The authors point out that the annual decrease of CO2 emissions of between 4.2 to 7.5% is comparable to the rate of decrease needed year on year over the next decade to limit climate change to 1.5°C, highlighting the challenge faced to limit climate change in line with the Paris climate agreement.
June 23, 2020
Blood type is associated with severity of COVID-19
A study published in the New England Journal of Medicine on June 17, 2020, reported on a genetic analysis of more than 1900 severely ill patients from Spain and Italy who had respiratory failure due to COVID-19. These severely ill patients were compared to over 2000 patients who were healthy, some of whom may have had COVID-19 but had only mild or no symptoms. Previous studies have suggested that a person’s blood type might influence COVID-19 susceptibility. Researchers identified a gene location that was common in many of the patients with respiratory failure due to COVID-19. This gene also overlaps with a gene that controls blood type. Further study found that people with type A blood had a significantly higher risk of respiratory failure due to COVID-19 compared to people with other blood types. Type O blood was protective. The findings do not indicate how blood types are related to respiratory failure in patients with COVID-19, but the findings do provide doctors with additional information to indicate which patients may be at higher risk of severe COVID-19.
June 18, 2020
Comorbidities increase death by a factor of 12 in COVID-19 cases
The June 15 early release issue of the US Centers for Disease Control, Morbidity and Mortality Weekly Report, describes demographic characteristics, underlying health conditions, symptoms, and outcomes among 1,320,488 laboratory-confirmed COVID-19 cases as of May 30, 2020. Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died. Among 287,320 (22%) of cases with data on individual underlying health conditions, the most common underlying health conditions were: cardiovascular disease 32%, diabetes 30%, and chronic lung disease 18%. Hospitalizations were 6 times higher and deaths 12 times higher among those with reported underlying conditions compared to those who reported no underlying conditions. The CDC feels that the findings highlight the need for continued community mitigation strategies, especially for the vulnerable populations.
June 17, 2020
Dexamethasone reduced deaths among patients with severe COVID-19
An Oxford University news release dated June 16, 2020, reported positive results of a clinical trial of 6425 patients with severe COVID-19. Patients were randomly assigned to receive either dexamethasone 6 mg once per day either by mouth or intravenous injection for 10 days (n = 2104) or usual care alone (n = 4321). Dexamethasone reduced the deaths by 1/3 in ventilated patients and by 1/5 in patients receiving oxygen only. Both results were highly statistically significant. Based on these results, one death would be prevented by treatment of 8 ventilated patients or about 25 patients requiring oxygen alone. There was no benefit among those patients who did not require respiratory support. In the news release, Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and one of the chief investigators for the trial said “Dexamethasone is the first drug to show improved survival in COVID-19.” It is important to note that the full data from the study have not yet been published or subjected to peer review, but outside experts immediately embraced the results. Patrick Vallance, the U.K. government’s chief scientific adviser, called the result “tremendous news” and “a ground-breaking development in our fight against the disease.” Scott Gottlieb, a former commissioner of the U.S. Food and Drug Administration, called it “a very positive finding.”
June 12, 2020
Striking decline in emergency department visits during the early parts of the pandemic
The COVID-19 pandemic has had a significant impact on the number of visits to the emergency room in the United States. A report published by the CDC in the Morbidity and Mortality Weekly Report on June 3, 2020, showed there was a decline in emergency visits by 42% during the early COVID-19 pandemic. The mean number of visits per week during the time frame from March 29 to April 25, 2020, was 1.2 million. Over the comparable time frame the previous year, March 31 to April 27, 2019, there were 2.2 million visits per week. The proportion of infectious disease related visits, however, was four times higher during this time period. The decreases were especially pronounced for children and females, and also in the Northeast part of the country. Visits for many conditions, including abdominal pain and other digestive symptoms, nonspecific chest pain and acute myocardial infarction (heart attack), and high blood pressure decreased during the pandemic, raising the concern that some individuals may be delaying care for conditions that might result in additional mortality if left untreated.
link to the study: https://www.cdc.gov/mmwr/volumes/69/wr/mm6923e1.htm?s_cid=mm6923e1_w
June 10, 2020
COVID-19 deaths rates put in perspectives
The New York Times reviewed the numbers of deaths in 25 cities and regions around the world during their most devastating months of the outbreak, setting those figures against their normal mortality levels, and then compared the increases to other natural disasters in history.
Increase in deaths during peak month compared to normal years:
- 7.3x 1918 Spanish flu in Philadelphia
- 6.7x COVID-19 in Bergamo, Italy
- 5.8x COVID-19 in New York City
- 4.0x COVID-19 in Lima, Peru
- 2.4x Hurricane Katrina in New Orleans
- 1.05x bad flu season in New York City
June 9, 2020
Dogs can detect COVID-19 by sniffing armpits, study claims
According to a study by French scientists and published in preprint June 5, 2020, on the bioRxiv server, dogs are able to detect the presence of COVID-19 by sniffing the axillary (underarm) sweat from infected patients. The researchers trained eight Belgian Malinois Shepherd dogs to identify people infected with the coronavirus from the odor samples taken from the armpits of more than 360 subjects. The samples were from healthy individuals and from those suffering from COVID-19. Overall, the dogs had a 95% success rate in identifying samples from COVID-19 patients. Dogs were familiarized with the odor of COVID-19 patients and trained to sit when they encountered it. The test involved each dog doing between 15 and 68 detections. Four dogs scored a hundred percent or a perfect score, while others achieved an accuracy rate of between 83 and 94%. On two occasions, the dogs indicated a positive result for samples that scientists had been told had come from healthy individuals not infected with the coronavirus. The researchers sent this information back to the relevant hospitals and the patients were retested, and the results this time came back positive for the virus.
The researchers chose underarm sweat because it is the most efficient in terms of chemicals in the body that evaporate into the air at room temperature and contains strong chemical signaling of disease. Also there is no detectable virus in the sweat which could possibly put the dog’s health at risk. This proof-of-concept study was based on the assumption that dogs, because of their advanced sense of smell, could be trained to discriminate COVID-19 positive people from negative ones by detecting certain specific metabolites produced by the SARS-Cov2 virus. Dogs' olfaction detection has proven to be effective in numerous situations. It is been used to detect explosives, drugs, and banknotes. It is also used in the early detection of human diseases and various cancers and to alert diabetic or epileptic people to hypoglycemia or imminent seizure. The authors hope to carry out a validation study and, if the sensitivity and specificity are high enough, then national authorities may use trained dogs to detect COVID-19 as a complementary method, specifically in settings where equipment or money are lacking to perform standard serology or RT-PCR testing.
link to the study: https://www.biorxiv.org/content/10.1101/2020.06.03.132134v1.full.pdf+html
June 8, 2020
About 1 in 3 adults use chemicals or disinfectants unsafely while trying to protect against COVID-19
There has been a sharp increase in calls to poison control centers regarding exposures to cleaners and disinfectants since the onset of the COVID-19 pandemic. To gain insight into this sharp increase and people's use, knowledge, and practices regarding these products, the Centers for Disease Control and Prevention (CDC) conducted an opt-in internet panel survey of 502 U. S. adults in May 2020.
The results were published in the agency's Morbidity and Mortality Weekly Report on June 5, 2020. The survey found that approximately 39% of the respondents engaged in non-recommended high-risk practices such as using bleach on food products, applying household cleaning and disinfecting products to the skin, and intentionally inhaling or ingesting these products. Respondents who engaged in high-risk practices more frequently reported adverse health effects they believed were caused by their use. "These practices pose a risk of severe tissue damage and corrosive injury and should be strictly avoided," the authors wrote in the paper. They concluded, "Although adverse health effects reported by respondents could not be attributed to their engaging in high-risk practices, the association between these high-risk practices and reported health effects indicates a need for public health messaging regarding safe and effective cleaning practices aimed at preventing SARS-CoV-2 transmission in households."
link to the study: https://www.cdc.gov/mmwr/volumes/69/wr/mm6923e2.htm?s_cid=mm6923e2_w#F2_down
June 4, 2020
First Human Trial of COVID-19 Antibody Drug
Eli Lilly, the Indianapolis-based pharmaceutical company, this week began the first human trial of a monoclonal antibody drug developed specifically against COVID-19. The medicine is a manufactured human antibody that duplicates an antibody found in the blood of a patient who recovered from Covid 19. The patient’s blood was screened using a new technology that identified more than 550 antibodies against the SARS-CoV-2 virus. Researchers then selected one that appeared particularly effective against the virus and began producing it in the laboratory. Antibody drugs must be given by vein but have the possibility of being able to help people recover from disease. They might also be used preventively in high-risk people exposed to disease before a vaccine is available.
link to the announcement: https://www.biopharmadive.com/news/eli-lilly-abcellera-coronavirus-antibody-drug-first-trial/57898
June 3, 2020
Timing of the COVID-19 test and the variability of false-negative results
In a study published in the Annals of Internal Medicine on May 13, 2020, researchers at Johns Hopkins University analyzed the results from seven previously published studies on the accuracy of the antibody test to determine whether a person has been exposed to the virus that causes COVID-19. Tests are not perfect. Results are sometimes normal in people who have the disease being tested for. That is, tests can have false-negative results. Results are sometimes abnormal in people who do not have the disease being tested for. That is, tests can have false-positive results.
Researchers found that the possibility of a false-negative result varied significantly with the timing of the test. Dates of testing ranged from the date of infection (the date of exposure), to the onset of symptoms (typically on day 5), and then dates after symptom onset. They discovered that the average probability of a false-negative result was 100% on the date of exposure, 67% on day 4, 38% on day of symptom onset, and 20% (lowest false-negative rate) on day 8 after exposure. After day 8, the probability of a false-negative result started to increase again. Therefore, the lowest false-negative rate was 8 days after exposure and 3 days after the typical onset of symptoms. The authors concluded that this may be the optimal time for testing if the goal is to minimize false-negative results.
link to the study: https://www.acpjournals.org/doi/10.7326/M20-1495
June 2, 2020
What sewage can tell us about the spread of COVID-19
Researchers have found large amounts of SARS-CoV-2 RNA, the genetic material for COVID-19, are excreted in the stool. Finding the viral signature of COVID-19 in sewage has allowed scientists to correlate the presence and amount of virus with disease spread and severity. Analysis of sewage can be a tool for disease surveillance and offers an easier way to gain a broader perspective of the pandemic without having to sample and test every person. In an article published in Smithsonian Magazine on May 14, 2020, Catherine J. Wu, a Boston-based science journalist and PhD in microbiology and immunology from Harvard University, discusses the recent research on how waste water can help track the spread of the COVID-19 virus, and the possible health implications of viral shedding in the feces, which then makes its way into the waste water system.
May 22, 2020
The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission
A study published on May 13, 2020, by the Proceedings of the National Academy of Sciences of the United States of America (PNAS) demonstrated that normal human speech emits droplets capable of lingering in the air. Researchers used lasers to emit an intense sheet of light to visualize bursts of speech droplets produced when subjects spoke the words "stay healthy." This light-scattering method provides visual evidence for speech droplet emission and also assesses their airborne lifetime. This method is particularly sensitive in measuring speech droplets with diameters less than 30 micrometers, which could remain airborne for longer than the larger droplets that have typically been the subject of research. They estimated that 1 minute of loud speaking generates at least 1000 virion-containing droplet nuclei that remain airborne for more than 8 minutes. Speech droplets generated by asymptomatic carriers are increasingly considered a likely mode of disease transmission. This direct visualization demonstrates how normal speech generates airborne droplets that can remain suspended for tens of minutes or longer and are eminently capable of transmitting disease in confined environments.However, it should be noted that this study does not address actual COVID-19 transmission.
link to the study: https://www.pnas.org/content/early/2020/05/12/2006874117
May 21, 2020
The CDC's advice for caring for someone sick at home
The Centers for Disease Control and Prevention (CDC) has recently published guidelines on caring for someone with COVID-19 at home or in a non-healthcare setting. The advice pertains to caring for people who are symptomatic with COVID-19 and for people who are asymptomatic but have tested positive. The recommendations are extensive and detailed. CDC provides helpful strategies on how to meet the basic needs of a person who is sick. CDC also identifies symptoms that may require emergency medical attention. CDC details ways caregivers can protect themselves.In the document, instructions can be found on how to limit contact with the sick person, how to handle meals, and when a sick person or caregiver is to wear face coverings or use gloves. Advice on handwashing, bathroom use, cleaning and disinfecting around the house, and doing the laundry is given. CDC also provides guidance on how to discontinue home isolation.
link to CDC guidance: https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/care-for-someone.html
May 19, 2020
COVID-19: Transmission explained
In a recent blog post, "The Risks-Know Them-Avoid Them," Erin S. Bromage, PhD, Associate Professor of Biology at the University of Massachusetts Dartmouth, explains the science of a contagious dose, where and how the virus spreads, and which environments are the riskiest. Dr. Bromage does an excellent job of translating data and findings into prose that non-scientists can more readily understand. Hopefully, a better understanding of how the COVID-19 virus spreads will help individuals make decisions about how to avoid becoming infected with the virus.
link to the blog post: https://www.erinbromage.com/post/the-risks-know-them-avoid-them
May 13, 2020
Pediatric multisystem inflammatory syndrome potentially associated with COVID-19
Boston Children’s Hospital has published a brief overview of a recently reported pediatric syndrome that may be related to COVID-19. In recent weeks, reports have come in from Europe and the Eastern US of a small number of seriously ill children with an inflammatory illness that affects several organ systems (termed pediatric multisystem inflammatory syndrome). Reports are still fragmentary, and descriptions of symptoms vary, but patients seem to have fever, varying degrees of organ dysfunction, and multiple laboratory markers of severe inflammation. The syndrome sometimes progresses to significant shock, requiring drugs to control blood pressure and mechanical ventilation.
There seems to be a connection to the current COVID-19 pandemic in that a number of the affected children have a positive test for SARS CoV-2. However, the connection remains unclear.
The syndrome bears some relationship to Kawasaki disease; however, not all manifestations of Kawasaki disease are present.
Although rare, the cases are quite severe. Affected children do seem to respond to treatment, so potentially affected children should be referred to a specialty center.
link to the overview: https://discoveries.childrenshospital.org/covid-19-inflammatory-syndrome-children/
May 8, 2020
SARS-CoV-2 was already spreading in France in late December 2019
Reverse transcription polymerase chain reaction (RT-PCR) testing was done on a stored sputum sample of a patient hospitalized in France in late December with severe acute respiratory syndrome. RT-PCR is a technique that allows researchers to determine how much RNA from a specific source is in a sample. The sample was found to be positive for coronavirus. This result revealed that the epidemic in France started much earlier than originally believed. This finding was published online in the International Journal of Antimicrobial Agents on May 3, 2020. The researchers examined the medical records of all patients admitted to their ICU with influenza-like illness between December 2, 2019, and January 16, 2020 (a total of 124 patients). They excluded patients with a positive PCR test for another respiratory virus and excluded patients with medical records that indicated findings that were not typical of COVID-19. Nasopharyngeal samples of the remaining 12 patients were tested. One sample was positive for COVID-19. The positive sample belonged to a 42-year-old Algerian immigrant with no history of travel or link to China. He presented to the emergency department on December 27, 2019, with hemoptysis (coughing up blood), cough, chest pain, headache, and fever, that had been developing for 4 days. It is notable that one of his children had an influenza-like illness prior to the onset of his symptoms. The paper includes the medical history, clinical presentation, laboratory findings, radiological findings, and clinical course of his illness. Researchers concluded the disease was already spreading among the French population at the end of December 2019.
link to the study: https://www.sciencedirect.com/science/article/pii/S0924857920301643
May 7, 2020
Study of the transmission of SARS-CoV-2 in close contacts
An epidemiological study of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China published in The Lancet, provides information on the natural history and transmissibility of the SARS-CoV-2 virus. Using a large primary data set, researchers were able to shed light on the incubation times, time to recovery, and transmissibility of the virus. Interestingly, they found the secondary attack rate in close contacts to average around 7%. Transmission between very close contacts, such as individuals sharing a household, was less than one in six contacts (ie, secondary attack rate of 11 to 15%).
The study highlighted the finding that children were as likely to become infected as adults. Although children frequently do not get sick, they should not be overlooked as a significant source of transmission. The study also demonstrated the value of contact-based surveillance in reducing the spread of the SARS-CoV-2 virus in the community.
link to the study: https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30287-5.pdf
May 5, 2020
Large-vessel strokes in young and middle-aged patients with COVID-19
The New England Journal of Medicine reported on April 28, 2020, on five cases of large-vessel stroke in patients 50 years of age or younger infected with COVID-19. The youngest was a 33-year-old woman.The report included all stroke patients younger than 50 at the Mount Sinai health system in New York City during a two-week period in late March and early April. The rate was nearly seven times the number of stroke patients in that age group during any average two-week period over the previous year and indicates a very strong correlation with COVID-19.
link to the news article: https://www.washingtonpost.com/health/2020/04/24/strokes-coronavirus-young-patients/
April 29, 2020
Yale University School of Public Health finds saliva samples promising alternative to nasopharyngeal swab
Yale University School of Public Health conducted a study comparing saliva and nasopharyngeal samples in 44 patients hospitalized with COVID-19 and 98 health care workers with occupational exposure to COVID-19 patients.The study was reported by Michael Greenwood on April 24, 2020, in Yale News. Although the study was small and limited, it showed great promise for using saliva samples in place of the current standard of using nasopharyngeal swabs.The study found that saliva yielded greater detection sensitivity and consistency throughout the course of infection when compared with patient-matched nasopharyngeal samples.There was also less variability in self-sample collection.This can be transformative in testing for COVID-19. Saliva testing is noninvasive, does not rely on nasopharyngeal swabs, and can be easily self-administered and therefore negates the risks, bottlenecks, and use of resources such as swabs and personal protective equipment (PPE), that direct patient contact and current testing practices use. The study has not been subject to peer review. The research results are currently available on the pre-print server medRxiv.
link to the study: https://www.medrxiv.org/content/10.1101/2020.04.16.20067835v1.full.pdf+html
April 28, 2020
WHO issues guidance on "immunity passports"
The World Health Organization (WHO) issued a brief warning (April 24, 2020) that there is no evidence that the presence of antibodies to the SARS-CoV-2 virus protects against reinfection and development of COVID-19 disease. The WHO cautions governments against using antibody testing to guide them on relaxing social measures and issuing “immunity passports” or “risk free certificates” that enable individuals to assume they are protected against re-infection. There are no guarantees that individuals who have had COVID-19, or have tested positive for antibodies, can return to work or travel risk-free. “At this point in the pandemic, there is not enough evidence about the effectiveness of antibody-mediated immunity to guarantee the accuracy of an 'immunity passport' or 'risk-free certificate,’ ” WHO said.
The WHO also emphasized that laboratory tests that detect antibodies to SARS-CoV-2 in people, including rapid immunodiagnostic tests, need further validation to determine their accuracy and reliability. Immunodiagnostic tests may falsely categorize people in two ways. The first is that they may falsely label people who have been infected as negative (false-negative) and the second is that people who have not been infected are falsely labelled as positive (false-positive). Each antibody test will need to have its accuracy (false-negative and false-positive rates) determined. Both errors have serious consequences and will affect control efforts.
link to the WHO announcement: https://www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19
April 27, 2020
Characteristics of patients hospitalized with COVID-19
A large case series of 5700 sequential patients admitted to New York City area hospitals between March 1 and April 4, 2020 with confirmed COVID-19 was published in JAMA Network online April 22, 2020. The study provides a comprehensive description of their presenting characteristics, comorbidities, and outcomes. Most notable is that many patients also had other medical problems such as high blood pressure (57%), obesity (42%) and diabetes (34%). At triage, only 31% had a fever. The study focused on the 2643 patients who were either discharged (2090) or died (553) during the study period. In this group of patients who reached these outcomes, 320 had received mechanical ventilation of whom 88% died, of those over age 65 who received mechanical ventilation 97% died. It should be noted that 3066 patients remained hospitalized at the time the outcome data was collected, and this certainly includes a number of patients over the age of 65 who required mechanical ventilation and had survived to that time.
link to the study: https://jamanetwork.com/journals/jama/fullarticle/2765184
April 24, 2020
Studies of hydroxychloroquine for COVID-19
The initial enthusiasm and early embrace of hydroxychloroquine has been tempered by concerns about efficacy and potential adverse effects. Several recent studies and reports are summarized (and mentioned below) in an April 21st online review article in Science (1), which highlights reasons for these concerns:
An analysis of the outcomes for 368 veterans hospitalized for COVID-19 and treated with hydroxychloroquine alone, hydroxychloroquine plus azithromycin, or no hydroxychloroquine was published on April 21 (2). This study showed no benefit in terms of reduced mortality or need for mechanical ventilation in the groups receiving hydroxychloroquine alone or in combination with azithromycin. The group receiving only hydroxychloroquine had an increase in death from all causes.
A Mayo Clinic Proceedings publication (3) on April 7 discussed the heart complications caused by chloroquine and hydroxychloroquine and provided guidance for doctors on monitoring for and avoiding this potentially lethal complication. The authors list risk factors for this complication and recommend screening for these factors before treatment, correcting risk factors that can be modified, and monitoring the patient’s heart during treatment.
A study at the New York University School of Medicine (4) looked at changes in the heart in 84 adult patients with SARS-CoV-2 infection treated with hydroxychloroquine plus azithromycin. In 11% of patients, significant heart changes occurred, representing a high risk for abnormal heart rhythms (arrhythmias).
In Brazil, a blinded, randomized clinical trial (5) of high- and low-dose chloroquine (given with ceftriaxone and azithromycin) in people hospitalized for COVID-19 was halted early after only 81 patients were enrolled when investigators found more deaths in the group getting the higher of the two doses of chloroquine.
1. Servick K: Antimalarials widely used against COVID-19 heighten risk of cardiac arrest. How can doctors minimize the danger? Science April 21, 2020. https://www.sciencemag.org/news/2020/04/antimalarials-widely-used-against-covid-19-heighten-risk-cardiac-arrest-how-can-doctors
2. Magagnoli J, Siddharth N, Pereira F, et al: Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. April 23, 2020. PREPRINT medRxiv available at https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v2. doi: https://doi.org/10.1101/2020.04.16.20065920
3. Giudicessi JR, Noseworthy PA, Friedman PA, et al: Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19). Mayo Clin Proc 2020 Apr 7 doi: 10.1016/j.mayocp.2020.03.024 [Epub ahead of print]
4. Chorin E, Dai M, Schulman E, et al: The QT interval in patients with SARS-CoV-2 infection treated with hydroxychloroquine/azithromycin. April 3, 2020. PREPRINT medRxiv available at https://www.medrxiv.org/content/10.1101/2020.04.02.20047050v1. doi: https://doi.org/10.1101/2020.04.02.20047050
5. Silva Borba MG, de Almeida Val F, Sampaio VS, et al: Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study). April 16, 2020. PREPRINT medRxiv available at https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v2 https://doi.org/10.1101/2020.04.07.20056424
April 23, 2020
Proposed national COVID-19 testing action plan
The Rockefeller Foundation has provided a comprehensive plan (dated 4/21/2020-see link below) to reopen workplaces and communities based on testing for COVID-19 and close follow-up of positive test results. The goal of the plan is to build a state-led national program of COVID-19 testing that supports reopening the economy through the goals of workforce monitoring, early detection of recurrent outbreaks, and diagnostic and home testing. The plan has 3 major components:
- Dramatically expand COVID-19 testing from the current 1 million tests per week to 3 million per week over the next 8 weeks and then to 30 million tests per week over the next 6 months. This will require investing in and bolstering test capacity at national, university, and thousands of small local labs across the country.
- Train and launch an army of healthcare workers to administer the tests and to do contact tracing for those with positive tests.They suggest this be organized around the state public health departments. They propose hiring 100,000 to 300,000 workers who will need to be supported by computer networks linked to many electronic health records.
- Integrate and expand federal, state, and private data platforms to facilitate real-time analyses and disease tracing. This will identify recurrent COVID-19 outbreaks and direct surges in testing volumes and follow-up.
This white-paper provided by the Rockefeller Foundation has many good ideas and is a must read. The massive plan will require integration of many scattered computerized data platforms. All this will need to balance privacy with the need for infection control.
April 21, 2020
28,000 missing deaths: tracking the true toll of the coronavirus crisis
A review of mortality data in 11 countries showing that far more people died in these countries than in previous years was reported by Jin Wu and Allison McCann in the New York Times on April 21, 2020. They estimated the excess mortality for each country by comparing the number of people who died from all causes this year with the historical average during the same period. The finding was that at least 28,000 more people have died during the coronavirus pandemic over the last month than the official COVID-19 death counts report. Since most countries report only those COVID-19 deaths that occur in hospitals there are many COVID-19 deaths that are unreported. The 28,000 excess deaths found in this study include deaths from COVID-19 as well as those from other causes, likely including people with other disorders who were not treated as hospitals became overwhelmed. This article suggests that the overall global death toll from COVID-19 will be much higher than the reports of deaths due to COVID-19 confirmed by testing. For impressive graphic presentation of these trends in each country please use the following link to the article.
link to the news article: https://www.nytimes.com/interactive/2020/04/21/world/coronavirus-missing-deaths.html?smid=em-share
April 16, 2020
Serosurvey by NIH requesting volunteers
To get a clearer picture of the magnitude of the COVID-19 pandemic in the United States, the NIH is enrolling as many as 10,000 volunteers. Individuals with a confirmed history of COVID-19 or current symptoms of COVID-19 are not eligible to participate. “This study will…tell us how many people in different communities have been infected without knowing it, because they had a very mild, undocumented illness or did not access testing while they were sick,” said Anthony S. Fauci, MD, NIAID Director. Researchers will collect and analyze blood samples for antibodies to Sar-CoV-2 S protein. Results will help illuminate the extent to which the virus has spread undetected in the population. Participants will be shipped at-home blood collection kits and provided detailed instructions on collecting a microsample of blood and mailing it back for analysis. People interested in joining the study should contact: email@example.com
April 15, 2020
Prominent scientists have bad news about coronavirus antibody tests
In response to infection, our bodies make antibodies to fight the infection. Antibody tests measure the presence of these antibodies, identifying a person who has been infected. However, although a positive test means a person has been infected, it may not necessarily mean the infection has been cleared from the body and if cleared, it may not guarantee protection against a repeat infection. Also, there are a number of different antibody tests, each varying in accuracy.
An article in CNN on April 15, 2020 reported that top scientists have briefed White House officials about problems identified with the antibody tests being developed for COVID-19. Elizabeth Cohen, a Senior Medical Correspondent for CNN, identified several issues with development of antibody tests in the US.
First, the FDA relaxed the rules so that companies can sell their antibody tests without showing how well they work. The American Public Health Lab Association says this has resulted in “crappy” tests flooding the market. There is concern that some tests may identify antibodies to the different coronaviruses that cause the common cold, thus giving false-positive test results for COVID-19.
Second, without careful regulation, good antibody tests cannot be distinguished from bad ones.
Third is the question as to what antibody level provides protection against getting infected again with COVID-19 and perhaps spreading the virus to others. Much study will be needed to answer this question, which has important implications for our society and economy.
Fortunately, it has been reported that FDA Commissioner Dr. Stephen Hahn said antibody tests would undergo scientific review.
April 14, 2020
Why coronavirus death rates can't be summed up in one simple number
Johnathan Fuller, MD, PHD, provides a clear article in which he explains the wider perspective on the ever-shifting COVID-19 statistics. In an April 10, 2020, article in the on-line journal, The Conversation, Dr. Fuller explains why statistics and models differ. His scholarship provides the reader with a framework and perspective to help interpret the large volume of epidemiological information being reported about the COVID-19 pandemic. Making the best decisions on public health policy and individual cases requires deeper understanding of the models than just the numbers alone.
link to the article: Why coronavirus death rates cant be summed up in one simple number
April 10, 2020
Can smart phone apps help beat pandemics?
An interesting article was posted April 9, 2020 by Dr, Francis Collins, Director of the National Institutes of Health (NIH). On the NIH Director's Blog, he discusses enlisting the use of smart phones for contact tracing and notification in fighting the COVID-19 pandemic. Traditional methods involving teams of public health workers speaking to people via phone or in face-to-face meetings is very time consuming. Lost time allows for infection to spread more widely because there is a delay in finding and notifying individuals exposed to the virus. By taking advantage of smart phones' wireless Bluetooth technology, digital tracing can improve the chances of keeping COVID-19 under control. In China, research showed a correlation between the use of contact-tracing apps and what appears to be sustained suppression of COVID-19 infection. Dr. Collins touches on major ethical, legal, and social issues.
link to the blog post: https://directorsblog.nih.gov/author/collinsfs/
April 9, 2020
A new antiviral drug heading into clinical trials offers hope for COVID-19 treatment
A new drug called EIDD-2801 shows promise in treating lung damage caused by the novel coronavirus Sars-CoV -2. EIDD-2801, a ribonucleoside analog with antiviral activity on the RNA-dependent RNA polymerase, was developed by researchers at UNC-Chapel Hill Gillings School of Global Public Health. Results from the most recent study were published April 6, 2020 online by the journal Science Translational Medicine. The published study found EIDD-2801 can protect cultured human lung cells infected with SARS-Cov-2. The drug also appears effective in treating other serious coronavirus infections. Experiments with mice found when EIDD-2801 is given 12 to 24 hours after onset of infection with viruses related to COVID-19 lung damage and weight loss were significantly reduced. An added advantage is that the drug can be given orally as opposed to other treatments that must be given intravenously. The ease of treatment offers the potential for treating less ill patients, or for prophylaxis.
link to the study: https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883
April 8, 2020
COVID-19 vaccine candidate shows promise, research shows
Interesting news from a story published in ScienceDaily
Scientists at the University of Pittsburgh School of Medicine announced a potential vaccine against COVID-19. The vaccine when tested in mice produced antibodies specific to Sars-CoV-2 at quantities sufficient for neutralizing the virus. The paper detailing the research appeared April 2, 2020 in EBioMedicine, which is published by Lancet. Using groundwork laid during earlier coronavirus epidemics, the vaccine targets the spike protein of the coronavirus. The vaccine is produced using lab-made pieces of viral protein to build immunity. It's the same way the current flu shots work. Researchers use a novel approach to deliver the drug, called a microneedle array, to increase potency. The co-senior author of the study stated that "testing in patients would typically require at least a year and probably longer."
link to the news article: https://www.sciencedaily.com/releases/2020/04/200402144508.htm
April 6, 2020
New report finds no benefit from the combination of Hydroxychloroquine and Azithromycin in patients severely ill with COVID-19
A small trial looking at the drug hydroxychloroquine, in combination with azithromycin on patients with severe symptoms found no evidence of strong antiviral activity or clinical benefit from the combination of drugs. There were only eleven patients in the study, eight of the patients had underlying conditions that placed them at poor risk. This trial is too small to allow meaningful statistical analysis or conclusions regarding efficacy or safety of the drugs. However, this report cast doubts about the antiviral efficacy of this combination in patients severely ill with COVID-19 as had been suggested by an earlier French study.
April 6, 2020
CDC recommends the Use of Cloth Face Coverings, Especially in Areas of Significant Community-Based Transmission
A significant portion of people who are infected with coronavirus lack symptoms and even those who eventually develop symptoms can transmit the virus to others before showing symptoms. This means that the virus can spread between people interacting in close proximity—for example, speaking, coughing, or sneezing—even if those people are not exhibiting symptoms. In light of this, the CDC recommends wearing cloth face coverings in public settings where other social distancing measures are difficult to maintain (e.g., grocery stores and pharmacies) especially in areas of significant community-based transmission. Use of simple cloth face coverings will slow the spread of the virus and help people who may have the virus and do not know it from transmitting it to others. Cloth face coverings fashioned from household items or made at home from common materials at low cost can be used as an additional, voluntary public health measure.
It is critical to emphasize that maintaining 6-feet social distancing remains important to slowing the spread of the virus.
The cloth face coverings recommended are not surgical masks or N-95 respirators. Those are critical supplies that must continue to be reserved for healthcare workers and other medical first responders, as recommended by current CDC guidance.
For the full CDC recommendations see: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover.html