Introduction
Since the discovery of the AIDS virus and its in vitro culture,
clinical observations have been supplemented or even replaced by
monitoring the blood or plasma viral load of patients with chronic
infections such as HIV and viral hepatitis. It is commonly accepted that
a decrease in the viral load attests to an improvement in the infection
or even to a cure (1), making it possible to use it to judge the
therapeutic effectiveness of new antiviral drugs. Indeed, this method is
widely used as a gold standard marker in randomised clinical trials (2).
In addition, viral load monitoring has been applied to monitoring the
effectiveness of treatments for acute viral infections such as
cytomegalovirus (CMV) (3) and Epstein-Barr virus (EBV) (4). Monitoring
viral load through quantitative PCR has been recommended as a way of
monitoring therapeutic efficacy (5). For example, the effectiveness of
EDP-938, a non-fusion replication inhibitor of respiratory syncytial
virus (RSV), was evaluated in a randomised controlled trial involving
volunteers who were intra-nasally inoculated with the RSV-A Memphis 37b
strain. This trial concluded that all EDP-938 regimens were better than
placebo in terms of lowering of the viral load (6). More recently,
several randomised trials on the treatment of COVID-19 have used viral
load as the primary outcome, demonstrating that ivermectin (7) reduced
SARS-CoV-2 viral load in comparison with convalescent plasma (8).
Metformin glycinate has been reported to reduce SARS-CoV-2 viral load in
a double-blind Phase IIb clinical trial (9). In a very preliminary
paper, we reported that 26 patients with COVID-19 treated with HCQ with
or without azithromycin had a significant shorter virus shedding period
compared to 16 untreated patients with COVID-19 (10). This paper was
severely criticised, and we published an additional paper responding to
these criticisms, in which we confirmed the reduction of the viral load
in patients treated with HCQ (11). Subsequently, in another
observational study, we reported that the persistence of viral shedding
over ten days was more frequent in patients who were not treated with
HCQ-AZ (12). A number of confounding factors may affect the outcome. The
viral clearance of SARS-CoV-2 has been reported to depend upon age,
given that the duration of shedding is shorter in younger patients
(13–15). Other confounding factors include the timescale between the
onset of symptoms and admission (16), being immunocompromised, and the
initial viral load (17). Armed with this new knowledge, we aim here to
re-analyse our database, investigating the role of HQC on the viral
shedding of patients with COVID-19.