Massachusetts may ultimately need 1.4 million tests for COVID-19 and have to conduct tens of thousands a day, Harvard infectious disease experts said Friday, adding their voices to a nationwide chorus calling to increase dramatically the pace of testing across the country.
“This is a scale that’s not anywhere near where we’re at right now,” said Pardis Sabeti, professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health and a researcher at the Broad Institute of MIT and Harvard.
Sabeti added that Americans have refused to learn preparedness lessons offered by Ebola, SARS, and other prior epidemics.
“The fundamental fact is … that we don’t focus on preparedness; we focus on reaction. Every time, again and again, we wait.
And there’s so many things that we could have in place so that we could move quickly.”
The anticipated rate of necessary testing is hundreds of times the level currently being done here.
Massachusetts Gov. Charlie Baker said on Saturday that 475 people had been tested in the state. On Sunday, the state said 26 additional cases had been detected, bringing the total to 164.
Baker on Sunday took the additional steps of closing restaurants in the state to on site eating, banning meetings of more than 25, and closing schools through April 7.
Sabeti said her lab had working diagnostics back in January, within days of receiving the virus’s genome from Chinese researchers, so there’s no reason why every hospital shouldn’t have had diagnostic tests ready to go now.
Instead, Food and Drug Administration (FDA) and other regulatory guidelines dictated that only state labs could do the testing.
“That was an incredible feat. They caught it early,” Sabeti said of Chinese researchers’ work on the virus.
“We had an opportunity to be well ahead of the game.”
The rollout of testing has been plagued with problems.
The Centers for Disease Control and Prevention’s (CDC) initial test kits were found to be flawed by early February, forcing a scramble to develop and gain FDA approval for new kits.
Since then, federal health officials agree, testing has been snarled in manufacturing problems and shortages of key chemicals, cotton swabs, and gloves, as well as red tape over allowing outside companies and academic labs to produce tests.
Over the last week, the Trump administration first promised, then walked back from promising tests for anyone who needs them. On Thursday, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, admitted to Congress that testing “is a failing. Let’s admit it.”
On Friday, the FDA approved a test by Swiss drugmaker Roche that can provide results in three hours.
Peter Slavin, president of Harvard-affiliated Massachusetts General Hospital, offered some hope, saying that MGH and Brigham and Women’s Hospital have been approved for and begun testing in their own hospital-based labs, though the initial numbers are small compared to the need, about 130 daily between the two institutions.
South Korea, which the World Health Organization recently praised for its handling of the crisis, has tested about 4,000 people per million of its population, Slavin said.
“Testing is the biggest problem that we’re facing,” Slavin said.
According to the World Health Organization, the global pandemic reached 153,000 cases in 143 countries Sunday, with 5,735 deaths. The U.S. reported 1,629 cases and 41 deaths.
Speakers said the problem in the U.S. is twofold. The U.S. Centers for Disease Control and Prevention’s guidelines for who can be tested remain restrictive, but even if they’re loosened the test supply is so inadequate that hospitals will have to ration testing to only the most likely COVID-19 cases.
“We should ideally be doing tens of thousands of tests per day,” said Lindsey Baden, the Brigham’s director of clinical research and an associate professor at Harvard Medical School.
“The criteria from the CDC made sense weeks ago, but I don’t think it makes sense currently, at what’s likely the transmission [rate today]. … We need to stand up testing for tens of thousands of people per day, and once we do that we’ll be in a very different place to be able to respond to this event.”
Over the last week, the Trump administration first promised, then walked back from promising tests for anyone who needs them. The image is credited to NIAID-RML.
The comments came at the close of a roundtable event at the Medical School, hosted by HMS Dean George Daley and featuring U.S. Sen. Ed Markey.
It brought together academic experts, health care leaders, and representatives of nurses, hospitals, and other key stakeholders.
During a news conference at the session’s close, Markey called on President Trump to declare a national emergency, which would free billions of dollars that could be used to both respond to the crisis and ease the economic pain felt by businesses and individuals in regions that have canceled major gatherings, closed schools, and otherwise interrupted lives and the commerce associated with them.
Late in the afternoon Trump declared the pandemic an emergency, freeing up $50 billion in federal money to combat the virus.
“There was a tsunami coming that we could see,” said Eric Rubin, the Irene Heinz Given Professor of Immunology and Infectious Diseases at the Chan School and editor of the New England Journal of Medicine, “and we hoped that it would go away before it reached us.”A
In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA.
Patient 1 – a woman in her 60s – returned from China in mid-January, 2020.
One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2.
Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2.
Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel.
Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2.
On Jan 23, 2020, Illinois, USA, reported the state’s first laboratory-confirmed case (index case) of COVID-19 in a traveller who returned from Wuhan in mid-January, 2020. Subsequently, the first evidence of secondary transmission in the USA was reported on Jan 30, when the husband of the index patient, who had not travelled outside the USA, tested positive for SARS-CoV-2. Public health authorities did an intensive epidemiological investigation of the two confirmed cases.
The Illinois Department of Public Health, Chicago Department of Public Health, Cook County Department of Public Health, and DuPage County Health Department consulted with the US Centers for Disease Control and Prevention (CDC) for technical assistance and invited a CDC field team to assist with onsite investigations after laboratory confirmation of the first case of COVID-19.
Patients with COVID-19 were defined as individuals with laboratory-confirmed SARS-CoV-2 infection.
Contacts were defined as people who reported or were identified to have potential exposure to a case on or after the day of symptom onset of the case (table 1). The earliest reported day with new symptoms was used as date of symptom onset.
The date of symptom onset for the index case is considered day 0 for the purposes of this investigation, and all subsequent dates will be described by day of investigation (DOI), starting with DOI 0.
In this Article, the numbers of contacts exposed to either case on or after the day of their first positive laboratory result are also presented.
Table 1 Illinois risk classification of health-care personnel and community contacts with potential exposure to COVID-19
|Community contacts||Health-care personnel contacts|
|Type of exposure||Example||Public health measure||Type of exposure||Example||Public health measure|
|High-risk contacts||Living in the same household as, being an intimate partner of, or providing care in a non-health-care setting (such as a home) for a person with symptomatic laboratory-confirmed COVID-19||Domestic partner||Home quarantine for 14 days after last exposure*; active symptom monitoring for 14 days after last exposure||Performing or being present in the room for a procedure likely to generate higher concentrations of respiratory secretions or aerosols while not using all recommended PPE†, or close contact while not wearing respiratory protection with a patient with laboratory-confirmed COVID-19 infection who was not wearing a facemask||Health-care personnel not wearing all recommended PPE who collected or were present for the collection of nasopharyngeal or oropharyngeal specimens‡||Home quarantine*; exclude from work; active symptom monitoring for 14 days after last exposure|
|Medium-high-risk contacts||Prolonged or frequent contact with a person with symptomatic laboratory-confirmed COVID-19§||Family members visited for prolonged periods or close work associates||Home quarantine for 14 days after last exposure*; active symptom monitoring for 14 days after last exposure||Prolonged (15 min or more) contact with a patient with laboratory-confirmed COVID-19 infection or their secretions or excretions while not using all recommended PPE†||Performing a check of the vital signs and phlebotomy on a masked patient while wearing gloves and a surgical mask||Exclude from work; active symptom monitoring for 14 days after last exposure|
|Medium-risk contacts||Close contact with a person with symptomatic laboratory-confirmed COVID-19 and not having any exposures that meet a high-risk or medium-high-risk definition||Colleagues who work less closely together but still have regular face-to-face contact||Active symptom monitoring for 14 days after last exposure||More than brief contact (>1–2 min) with a patient with laboratory-confirmed COVID-19 infection or their secretions or excretions while not using all recommended PPE† that does not meet a high-risk or medium-high-risk definition||Examined patient for 5 min while wearing mask, gown, gloves, and faceshield (but no respirator)||Exclude from work; active symptom monitoring for 14 days after last exposure|
|Low-risk contacts||Being in the same indoor environment with (or within 2 h of) a person with symptomatic laboratory-confirmed COVID-19||Shared a hospital or outpatient waiting room or entered space within 2 h of a case||Active symptom monitoring for 14 days after last exposure||Any duration of contact with a patient with laboratory-confirmed COVID-19 while using all recommended PPE†, brief interaction with the patient (1–2 min) not involving direct contact while not using all recommended PPE†, or working at the same time and location as a confirmed case but unsure whether they were in the same room||Examined patient while wearing gloves, gown, faceshield, or goggles and appropriate, fit-tested respiratory protection; entered patient’s room briefly to bring the patient a drink but did not have direct contact with the patient or their secretions or excretions||Active symptom monitoring for 14 days after last exposure|
|Non-contacts||Interactions with a person with symptomatic laboratory-confirmed COVID-19 that do not meet high-risk, medium-high-risk, medium-risk, or low-risk conditions||Walking by a patient in a corridor||None||Did not meet any of the high-risk, medium-high-risk, medium-risk, or low-risk conditions||Walking by a patient in a corridor||None|
COVID-19=coronavirus disease 2019.
PPE=personal protective equipment.
CDC=US Centers for Disease Control and Prevention. MERS-CoV=Middle East respiratory syndrome coronavirus.*
Implemented after identification of the second case of laboratory-confirmed COVID-19 in Illinois on Jan 30, 2020.†
Recommended PPE includes respiratory protection (ie, respirator), goggles or faceshield that covers the front and sides of face, gloves, and a gown.‡ Risk categorisation was developed on Jan 26, 2020, before published guidance from CDC for COVID-19.10
Criteria were based on published MERS-CoV guidance and additional input from CDC subject matter experts. Close contact was defined as being within approximately 6 feet or within the room or care area of a confirmed COVID-19 case (including sharing a health-care waiting area or room), or being in a shared air space vacated by a confirmed case within the previous 2 h. Transient interactions, such as walking by confirmed case, were not considered close contact.
Of note, nasopharyngeal and oropharyngeal specimen collection were not listed as aerosol-generating procedures in the CDC guidance, but were included as high-risk exposures in this investigation.
Risk categorisation was developed on Jan 31, 2020, before published guidance from CDC for COVID-19.11 Criteria were based on published MERS-CoV guidance and additional input from CDC and state and local health officials.
The medium-high-risk classification was included owing to the identification of some community contacts who did not meet the highest category of exposure risk but were nevertheless concerning.
Patients with COVID-19 were interviewed using a standardised questionnaire to identify symptom history, locations visited while symptomatic, and individuals with whom they had contact while symptomatic.
The Illinois COVID-19 Investigation Team, comprised of local and state public health staff and the CDC field team, worked with locations visited (eg, workplaces, retail establishments, or health-care facilities) by patients with COVID-19 to identify additional individuals who might have had exposures to SARS-CoV-2.
To identify possible exposures in health-care personnel, patient logs and staffing records were obtained and reviewed for all health-care settings visited by patients with COVID-19. Security footage was reviewed to identify additional health-care personnel and patients who had contact with patients with COVID-19 during transport through the admitting hospital.
Health-care personnel were defined as all people working in health-care settings who had the potential for exposure to infectious materials,12 including members of the Illinois COVID-19 Investigation Team.
All other contacts were classified as community members, including patients in the same indoor environment in a health-care setting (eg, a hospital waiting room).
Exposure risk classification
Health-care personnel and community members with potential exposure to SARS-CoV-2 were interviewed using standardised contact questionnaires to assess exposure and whether the individual had true contact with a patient with COVID-19.
Exposure risk was classified according to frameworks designed by members of the Illinois COVID-19 Investigation Team in consultation with CDC subject-matter experts (table 1).
These frameworks were based on published guidance for Middle East respiratory syndrome coronavirus and designed and implemented before interim risk assessment guidance for COVID-19 released by CDC.10, 11
Active monitoring of contacts
All health-care personnel and community contacts assessed to have had low-risk, medium-risk, medium-high-risk, or high-risk exposures were enrolled in active symptom monitoring, which continued for 14 days after last exposure to a patient with COVID-19.
Active symptom monitoring was done using Research Electronic Data Capture software (Vanderbilt University, Nashville, TN).
Contacts received automated, twice-daily emails inquiring about symptoms, including cough and shortness of breath, and a request for a self-measured temperature. If symptoms or fever (temperature of >38°C) were reported, or if contacts did not respond or declined email monitoring, public health officials telephoned contacts daily.
For hospital-based health-care personnel not excluded from work, pre-shift symptom assessment for fever, cough, or shortness of breath was implemented by hospital occupational health services.
To identify any contacts (including those that could not be reached for active symptom monitoring) seeking care for fever, cough, or shortness of breath at an emergency department, the Illinois Department of Public Health used locally available, near real-time surveillance data received from regional acute care hospitals, which included symptom and diagnoses data and personally identifiable information for matching.
If a contact developed fever, cough, or shortness of breath during active symptom monitoring, they were classified as a person under investigation (PUI; a standard case designation used by CDC during an outbreak)13 and were isolated and tested for SARS-CoV-2.
Specimen collection and laboratory testing
For PUIs, specimens were collected and sent to CDC for testing. Specimens included upper (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum) if spontaneously produced.
For patients with COVID-19, nasopharyngeal, oropharyngeal, serum, sputum, urine, and stool specimens were collected and sent to CDC for testing at initial presentation, and then every 2–3 days.
Additionally, a convenience sample of 32 asymptomatic health-care personnel contacts had one-time nasopharyngeal and oropharyngeal specimens obtained at least 7 days from their highest-risk exposure.
All health-care personnel contacts were offered testing, but laboratory capacity and availability of health-care personnel to undergo testing were limited in the setting of this urgent investigation.
Before Patient 2 reported symptoms to public health investigators, nasopharyngeal and oropharyngeal swabs were also collected from Patient 2 owing to his high-risk exposures to Patient 1.Specimens were collected per CDC guidance.14
All specimens were refrigerated at 2–8°C before shipping on icepacks to CDC. CDC did real-time RT-PCR (rtPCR) to detect three separate genetic markers of SARS-CoV-2, as previously described.15 T
he cycle threshold value ranges for the three markers were interpreted as a semi-quantitative measure of the RNA concentration in the specimen.
Role of the funding source
There was no funding source for this study.
Patient 1 is a female in her 60s who travelled to Wuhan on Dec 25, 2019, and returned to Illinois on Jan 13, 2020, and who was not symptomatic while travelling.
In Wuhan, she visited a hospitalised relative regularly and visited other family members who had undiagnosed respiratory illnesses, one of whom was later hospitalised with viral pneumonia.
No contacts had laboratory-confirmed COVID-19, but it is unknown whether any were tested for SARS-CoV-2.On DOI 6, she sought care at an outpatient clinic for fever, fatigue, and cough and was hospitalised that day for pneumonia.
She was reported to public health authorities as a PUI on DOI 7. Retrospectively, she reported that her symptoms, which also included nausea, abdominal discomfort, and dizziness, started as early as 6 days before admission (figure).
Before hospitalisation, she had frequent, close contact with her husband on DOI 0–6 when she had an active cough.
Her husband had not travelled to Wuhan. She and her husband live together, eat together, share a bed, and have frequent face-to-face interactions. Facemasks or other personal protective equipment (PPE) were not used at the home.
Her husband was classified as having high-risk exposures and began active symptom monitoring on DOI 7 with specimen collection on DOI 11, before his report of any new symptoms.
Patient 2 has chronic obstructive pulmonary disease, with a chronic, productive cough and baseline dyspnoea; therefore, the timing of symptom onset related to COVID-19 was difficult to determine (figure).
When first interviewed as a contact on DOI 7, he reported no fever or change in chronic respiratory symptoms. Later, he reported increased dyspnoea and sputum production starting on DOI 11, which was also the first day of specimen collection as a contact in Patient 1’s investigation.
Upon further interview of Patient 2’s contacts, it was suggested that some non-specific symptoms might have started as early as DOI 3, with fatigue and worsening cough. On DOI 14, he reported new haemoptysis and worsening dyspnoea through active monitoring. He was promptly admitted to the hospital and placed in an airborne infection isolation room (AIIR).
Nasopharyngeal and oropharyngeal specimens from DOI 11 tested positive for SARS-CoV-2 on DOI 15.On hospital admission, vital signs, and physical examination for Patient 1 were within normal limits.
Her chest radiograph demonstrated no abnormalities, but a CT scan of her chest revealed bilateral multifocal infiltrates and mediastinal and hilar lymphadenopathy. On admission, Patient 2 had mild tachypnoea and coarse breath sounds with mild wheezes bilaterally, although whether these signs represented a change from his baseline status is unclear. Patient 2’s chest radiograph showed emphysematous changes and right lower lobe infiltrates consistent with pneumonia.
For both patients, testing for other viral and bacterial respiratory infections was negative. Both experienced mild leukopenia (Patient 1 white blood count nadir 3·0 × 103 cells per μL, Patient 2 nadir 3·4 × 103 cells per μL), lymphopenia (Patient 1 absolute lymphocyte count nadir 0·7 × 103 cells per μL, Patient 2 nadir 0·8 × 103 cells per μL), and mild elevations in aspartate aminotransferase and alanine aminotransferase (Patient 1 peak 46 units per L and 66 units per L, Patient 2 peak 47 units per L and 75 units per L).
No other remarkable laboratory results were noted.Both patients recovered and were discharged to home isolation on DOI 23. Hospital admission was extended while arrangements were made for home isolation.
Home isolation for both patients was lifted on DOI 33, following two sets of negative respiratory specimens collected 24 h apart.Patient 1 wore a facemask in the emergency department waiting room and was placed on droplet precautions in the emergency department and for the first 10 h after admission.
She was subsequently transferred to an AIIR, where health-care personnel entering the patient’s room were required to adhere to Standard, Contact, and Airborne Precautions, including hand hygiene, gloves, gown, respirator, and eye protection.16
Health-care personnel were enrolled in active monitoring, and potential breaches were recorded and investigated to determine risk classification. Patient 2 was immediately evaluated and admitted to an AIIR and placed on Transmission-Based Precautions as described for Patient 1.
For Patient 1, initial nasopharyngeal, oropharyngeal, and sputum specimens collected on DOI 7 were positive, whereas serum and urine were negative. Her initial sputum rtPCR cycle threshold values ranged between 24–25, indicating high viral burden before isolation.
Sputum specimens remained positive longer than all other specimens for both cases (figure, appendix pp 3–4).
Stool specimens collected for Patient 1 also remained positive longer than nasopharyngeal and oropharyngeal specimens; however, Patient 2 had no positive stool specimens. Neither Patient 1 or 2 had serum or urine specimens that tested positive for SARS-CoV-2.372 contacts of either Patient 1 or Patient 2 were identified. Public health investigators were able to assess exposure risk and actively monitor symptoms for 347 (93%) of the 372 contacts, including 222 (94%) of 236 contacts with exposure on or after the date of first positive specimen collection.
There were 25 people that had insufficient contact information to complete active monitoring. None of these individuals were found to have emergency department visits with fever, cough, or shortness of breath using near real-time surveillance data received from regional acute care hospitals for 14 days after their last exposure.
Data presented are for those actively monitored. Of these 347 contacts, 195 (56%) were health-care personnel and 152 (44%) were community members. Although the majority of monitored contacts (228 [66%] of 347) had low-risk exposures, 119 (34%) had exposures of medium risk or greater (table 2).
Table 2Actively monitored contacts and PUIs owing to contact with a patient with COVID-19, Illinois, USA, 2020
|Since first reported date of symptom onset||On or after date of first positive specimen|
|Total contacts||Did not become a PUI||Met PUI criteria*||PUIs positive for COVID-19†||Total contacts||Did not become a PUI||Met PUI criteria*||PUIs positive for COVID-19†|
|Health-care personnel contacts|
Data are n or n/N. PUI=person under investigation. COVID-19=coronavirus disease 2019.* US Centers for Disease Control and Prevention PUI criteria for contacts of a confirmed case: fever (subjective or objective) or signs or symptoms of lower respiratory illness (eg, cough or shortness of breath).† PUIs were tested for COVID-19 using real-time RT-PCR for severe acute respiratory syndrome coronavirus 2. Only results from PUIs tested for COVID-19 in this investigation are presented here.‡ The index patient, Patient 1, is excluded from this total
Although Patient 1 and 2 live together and were hospitalised in the same facility, and therefore shared several common contacts (65 shared community contacts from emergency department or outpatient waiting rooms and 28 health-care personnel who interacted with both patients), they also had many unique contacts.
Patient 1 had 92 unique health-care personnel contacts and 16 unique community contacts, including one household contact (Patient 2).
Patient 2 had 75 unique health-care personnel contacts and 71 unique community contacts, including 51 from outpatient waiting rooms.
The majority of contacts (303 [87%] of 347 total monitored contacts and 195 [88%] of 222 monitored contacts on or after the date of first positive specimen collection) did not develop symptoms consistent with PUI criteria.
Additionally, surveillance data from Illinois acute care hospitals indicated that no asymptomatic monitored contacts or other contacts who could not be reached for active symptom monitoring presented to an emergency department with fever, cough, or shortness of breath during DOI 6–30.
During active symptom monitoring, 44 (13%) of 347 total contacts became PUIs, including 27 (12%) of 222 monitored contacts who had exposures on or after the date of first positive specimen collection.
As a household contact, Patient 2 was the only community member who had a high-risk exposure.
He became a PUI and subsequently the only other patient with COVID-19 in this investigation. Of the remaining 43 PUIs, all tested negative for SARS-CoV-2 while symptomatic; 32 of these PUIs were health-care personnel and 11 were community contacts.
Although 18 (41%) of 44 PUIs had low-risk exposures, 26 (59%) had exposures of medium risk or greater.32 health-care personnel contacts who were not PUIs had one-time nasopharyngeal and oropharyngeal specimens collected 7–14 days after their highest-risk exposure.
All of these exposures occurred on or after the date of first positive specimen collection of a patient with COVID-19. 21 (66%) of these asymptomatic health-care personnel had exposures of medium risk or greater.
All were negative for SARS-CoV-2 at the time of testing.
Source: Harvard – THE LANCET JOURNALS