THE director general of Health announced on May 26 that Malaysia will change its Covid-19 protocol and discharge patients after 14 days even if their RT-PCR is positive. Patients will be advised to undergo home quarantine for another 14 days. This follows a World Health Organization (WHO) report that those who have been infected for more than 14 days will have zero infectivity.
The netizens’ comments on an online article raised valid concerns: “Where is this report?”; “WHO has been proven wrong before”; “How do you count the 14 days?”; “Heading for disaster”; “Sending them home to die?”; “What if they infect others?”; “Quarantine them with a dog, see if the dog falls sick and test the sick dog”; “More lockdown?”; “We are broke”; “Scary”; “Doesn’t Malaysia have experts? Tedros ain’t a medical doctor”.
Jonah2’s spot diagnosis, “If you are following WHO, you are a confirmed idiot …”
Where is the science? Are netizens justified in throwing rocks at our rock star DG?
Google search did not yield any WHO report on this issue. However, on May 23, the National Centre for Infectious Diseases and the Chapter of Infectious Disease Physicians, Academy of Medicine, Singapore issued this Position Statement after carefully reviewing the latest publications, ‘Period of Infectivity to Inform Strategies for De-isolation for Covid-19 Patients’.
The summary and conclusion are as follows: “Based on the accumulated data since the start of the Covid-19 pandemic, the infectious period of SARS-CoV-2 in symptomatic individuals may begin around two days before the onset of symptoms, and persists for about seven to 10 days after the onset of symptoms. Active viral replication drops quickly after the first week. Viable virus was not found after the second week of illness despite the persistence of PCR detection of RNA. These findings are supported by epidemiologic, microbiologic and clinical data.
“These new findings allow for revised discharge criteria based on the data on the time course of infectiousness rather than the absence of RNA detection by PCR testing, taking into consideration both the clinical and public health perspectives, including the individual patient’s physical and mental well-being. In addition, given these findings, resources can focus on testing persons with acute respiratory symptoms and suspected Covid-19 in early presentation, allowing timelier public health intervention and containment.”
RT-PCR tests
So far, the most reliable test for the diagnosis of Covid-19 is the RT-PCR test using nasopharyngeal swabs or airway specimens, including throat swabs and saliva. A variety of RNA gene targets (viral envelop, nucleocapsid, spike etc) are used by different manufacturers.
On Feb 11-12, WHO organised a forum to identify research gaps and priorities for Covid-19, in collaboration with GloPID-R (Global Research Collaboration For Infectious Disease Preparedness). One of the eight immediate research needs agreed upon as part of the forum was to “mobilise research on rapid point of care diagnostics for use at the community level”. This recognition underscores the urgent need for access to accurate and standardised diagnostics for SARS-CoV-2, which can be deployed in decentralised settings.
The WHO is continually updating its technical guidance for Covid-19, including guidance on laboratory testing. The Geneva-based non-profit Foundation for Innovative New Diagnostics (FIND) is working closely with WHO and other partners to provide support on training, technical assistance, and capacity building to ensure access to accurate and high-quality diagnostic testing for SARS-CoV-2.
On Feb 19, FIND launched an expression of interest (EOI) for test developers of in vitro diagnostics (IVDs) that detect SARS-CoV-2 nucleic acid (molecular tests). The EOI closed on March 9 and 220 submissions were received for evaluation.
FIND conducted independent evaluations at the University Hospitals of Geneva (HUG), to verify the limit of detection (LOD) and the clinical performance (as reported by the manufacturers) of these molecular test kits. Test results can be checked on its website.
SARSCo2 RT-PCR tests for RNA fragments, not viable or infectious virus. To prove infectivity, viral culture and epidemiological studies are needed.
In most symptomatic Covid-19 individuals, nasopharyngeal swab viral RNA becomes detectable as early as day one of symptoms and peaks within the first week of symptom onset. This declines by week three, when most mild cases yield a negative result. In severely ill hospitalised cases, positivity may persist beyond three weeks.
The time course of RT-PCR positivity may vary with children or immunosuppressed groups, and for asymptomatic undiagnosed individuals. It is not known how long potential immunity lasts.
Virological assessment
Wölfel et al (Virological assessment of hospitalised patients with Covid-19.
Nature 2020. Published online April 1, 2020) reported a detailed virological analysis of nine cases that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak on day four.
Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples, in spite of high concentrations of virus RNA. Blood and urine samples never yielded the virus. The shedding of viral RNA from sputum outlasted the end of symptoms.
Seroconversion (positive antibody test) occurred after seven days in 50 per cent of patients and by day 14 in all patients but was not followed by a rapid decline in viral load. Infectious virus was cultured from throat and lung specimens in the first week of symptoms, but none after day eight in spite of high viral loads detected by regular PCR.
The Singapore NCID data, based on an analysis of 766 patients, showed that by day 15 from the onset of illness, 30 per cent of all Covid-19 patients are PCR-negative on nasopharyngeal swab. This rises to 68 per cent by day 21 and 88 per cent by day 28. By day 33, 95 per cent of all patients are negative by PCR.
The Singapore position paper quoted a local study from a multi-centre cohort of 73 Covid-19 patients, virus could not be isolated or cultured after day 11 of illness.
Epidemiological studies of infective period
A Hong Kong study of 77 infector-infectee pairs estimated that the infectious period started 2.3 days before onset of symptoms, peaking at 0.7 day, and declining within seven days. (He et al Temporal dynamics in viral shedding and transmissibility of Covid-19. Nature Med 2020).
Taiwan traced 2,761 close contacts of 100 Covid-19 patients and identified 22 paired index-secondary cases. All 22 cases arose from contact with the index case within five days of symptom onset and none (0 cases from 852 contacts) arose from contact five days or after. (Cheng HY et al. Contact tracing assessment of Covid-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset. JAMA Intern Med 2020 May 1).
RT-PCR test
On May 21, the Korean CDC revealed the findings from the investigation of 285 out of 447 cases who tested positive for RTPCR after being discharged negative. Of the 285 Re-Positive cases, 44.7 per cent were symptomatic for cough or sore throat.
Virus isolation in cell culture of respiratory samples of 108 re-positive cases, were all negative of their 790 close contacts, no secondary case has been found directly arising from this ‘re-positive period’.
On average, it took 44.9 days (eight to 82 days) from initial symptom onset to testing positive again after discharge. It took 14.3 days (one to 37days) from discharge to re-test positive.
While this study is ongoing, the Korea CDC was sufficiently confident to recommend a change to existing protocols effective May 19. For confirmed cases after discharge from isolation, the 14-day self-isolation will no longer be needed, nor will PCR test be required if symptoms occur within 14 days of discharge from isolation. The cases that test positive after discharge from isolation will no longer be isolated as confirmed or quarantined as contacts of infected cases.
However, reporting and investigation of re-positive cases and their contacts will continue as before for purpose of research and evaluation. So, they have changed the term ‘re-positive’ to ‘PCR detected after discharge from isolation’.
In Singapore, 18 positive cases were found to be persistently positive for between 38 to 51 days while isolated in a community care facility. They were clinically well.
Discharge RTPCR positive cases
The Malaysian national hammer thrower Jackie Wong, who tested Covid positive on March 16, was admitted to the Sibu Hospital. Following the previous Ministry of Health Malaysian protocol, he could not be discharged till at least two consecutive nasal swabs tested negative for RTPCR over 24 hours. His RT-PCR tests had been on and off positive over the 70 days, although he showed no symptoms. He (and his coach) was ecstatic to be finally discharged on May 27 following this new protocol.
As of May 31, Sarawak has 552 confirmed cases (first case March 13) with 508 discharged and 17 deaths. There were 27 still hospitalised in the four quarantine Hospitals.
According to a statement by SDMC secretariat, out of the 552 positive cases, 19 were those who were readmitted to the hospital because they have been tested positive of the virus again.
More Covid-19 cases will be discharged based on this new protocol, which will free up wards and staff who have been drafted into Covid duty. Certain sections of the hospitals, outpatient clinics, diagnostic and laboratory facilities can be safely reopened and staffed to handle the backlog of all the postponed operations, cancer cases, and all the other so-called ‘non-urgent cases’, which have been put on hold.
After all, hospitals are not safe places to hold up recovering patients who are asymptomatic but whose nasal swabs refuse to go negative or become positive weeks later. In their recovery stage they may pick up other hospital germs (nocosomial infections).
According to the Institute of Ageing, you can lose up to 1 per cent of lean muscle mass each day you spend in bed. Spending three to five weeks immobilised can lead to 50 per cent decrease in muscle strength.
Take home message
The recovery phase RTPCR positive doesn’t mean the person is infectious.
Viral cultures are usually negative from as early as the 10th to 11th day of illness, even though the RTPCR may remain positive for two to six weeks. In re-positives or persistently positive cases, the RTPCR test could be picking up dead viral components, which are no longer transmissible nor infective to others.
The actual on-the-field performance and accuracy of all diagnostic tests for Covid-19, between brands, within countries and laboratories, is being intensely scrutinised and audited. Interpreting findings of studies by different groups and extrapolating conclusions, is thus a tough, calculated judgement call every country’s director-general of Health has to make. The jury is still out. Netizens, hold on to your rocks.
Dr Tan Poh Tin is a public health trained paediatrician who has retired from the Ministry of Health and Universiti Malaysia Sarawak.