Almost 30 doctors have signed a letter to President Cyril Ramaphosa, appealing for him to lift the hard lockdown, arguing that the negative effects are "innumerable".
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"Our healthcare system and the economy were already on their knees at the outbreak of Covid-19," the letter, signed by 27 medical professionals overnight, reads.
"Many patients without Covid-19 are not getting the treatment they require due to the hospitals being emptied for Covid-19 patients. Many of these patients are avoiding hospitals and having their out-patient appointments cancelled.
"Disruptions in regular prevention programmes, such as immunisation schedules for infants or sexual and reproductive health promotion will undercut our few hard-won health gains since democracy. Together these are steadily building up a backlog of health care that is potentially a crisis in itself."
Last month, Ramaphosa announced an initial three-week lockdown which started on 27 March.
Aimed at curbing the spread of the coronavirus, the lockdown was later extended by two weeks.
The letter to Ramaphosa was compiled by graduates from the University of Cape Town's MBChB 1993 class, and their argument was "informed by extensive discussions and sharing of experiences and evidence".
The signatories argue that South Africa has "bought into an international rhetoric which is a poor fit for local circumstances".
The virus kills many elderly, a relatively small percentage of the population, it pointed out.
"At this stage, we do not know the effects on people living with HIV who are not on treatment and those with TB. If at all, a vaccine is unlikely to be developed and distributed within less than 18 months. Our economy and our healthcare system will be destroyed if we wait much longer and as always, our poorest citizens will suffer the most," the letter reads.
"Although current estimates of mortality are more than six times less than initially estimated, at 0.5%, we are approaching winter and there are a myriad reasons why the pandemic will hit South Africans harder in winter months. We cannot afford to stay on hard lockdown any longer. Each week that we delay is likely to worsen the outcome of the pandemic."
The doctors "strongly urge" that most people return to work as the health-related, social and financial side effects start to mount.
"Those who can work from home or in isolation should be encouraged to do so, but we feel it is critical that the fit and robust return to work, in a staggered fashion wherever possible.
"Close attention should be given to ensuring that public transport operators adhere to the revised regulations to minimise the transmission risk to their passengers."
Businesses where people congregate - such as bars and clubs - should remain closed, as should any meetings of groups of people, it agreed.
"Some restriction on the sale of alcohol during this crisis probably continues to make sense, as it likely reduces the burden on hospitals from alcohol related traffic-accidents and violence resulting in trauma," the letter reads, while people withdrawing from alcohol could consult doctors for help.
Under the lockdown regulations, the sale of liquor is illegal.
Ramaphosa is due to address the nation on Tuesday evening on the ongoing talks around policies to assist the ailing economy.
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