2. Diseases caused by hantaviruses
Hantaviruses pathogenic to humans have been classified into Old World
hantaviruses (OWHVs) and New World hantaviruses (NWHVs) based on their
geographical distribution. OWHVs, the major etiological agents of HFRS,
include HTNV, SEOV, and DOBV viruses, which are distributed in Asia and
Europe. NWHVs, the major etiological agents of HCPS/HPS, include ANDV
and SNV viruses, which are distributed in South America and North
America.4 Globally, about 150,000 to 200,000 HFRS or
HCPS/HPS cases are reported annually, with case fatality rates (CFR)
between 1%−15% (HFRS) to 30%−50% (HCPS/HPS).5
HFRS was first documented in Korea in 1951.2 This
disease is usually divided into five phases, including fever,
hypotension, oliguria, polyuria, and recovery, with the hallmark feature
of acute kidney injury, after the incubation period of
2−3 weeks. Acute kidney injury may
cause kidney swelling, proteinuria, and hematuria.6Symptoms of HFRS include fever, headache, low back pain, visual
impairment, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea,
and bloody stool), and proteinuria.3 Meanwhile,
hemorrhagic symptoms caused by thrombocytopenia include petechiae of the
skin and mucosa, hematuria, hemoptysis, conjunctival congestion,
gastrointestinal bleeding, and even intracranial hemorrhage.
Disseminated intravascular coagulation (DIC) may also occur in severe
HFRS cases. The hypotension phase is characterized by sudden hypotension
and shock caused by microvascular leakage, which may lead to sudden
deaths.5 The oliguria phase is caused by renal
failure, with the symptoms of oliguria (usually <400 mL/day)
and proteinuria. In the diuretic
phase, renal function gradually recovers with an increase in urine
output. While renal function can recover completely after a long
recovery period, chronic renal failure and hypertension may also
occur.7 In addition to the typical renal disease
caused by HFRS, some patients present with extrarenal symptoms, such as
acute respiratory distress syndrome (ARDS), cholecystitis, pericarditis,
and encephalitis.6 Infection with PUUV in humans can
lead to a mild form of HFRS termed nephropathia epidemica
(NE).8
HCPS/HPS was first documented in North America in
1993.3 This disease is usually divided into the
prodromal, cardiopulmonary, and recovery phases, with the hallmark
features of microvascular leakage and ARDS, after the incubation period
of 1−7 weeks.3 The prodromal symptoms are similar to
the fever phase of HFRS, such as fever, headache, myalgia, nausea, and
vomiting. It also includes flu-like symptoms (e.g., cough and dyspnea)
accompanied by thrombocytopenia.5 The cardiopulmonary
phase lasts for several days with tachycardia, arrhythmias, and
cardiogenic shock. Leakage of pulmonary capillaries in this phase can
cause respiratory failure, pulmonary edema, hypotension, bilateral
pulmonary infiltration, and pleural effusion. Acute kidney injury and
proteinuria also occur in some HCPS/HPS patients. HCPS/HPS can lead to
acute deaths during the cardiopulmonary phase.9
HTNV was first discovered in South Korea in 1978.10HTNV is mainly distributed in China, South Korea, Russia, and
Vietnam.5,11 More than 90% of global HFRS cases are
reported from mainland China, with most of them being caused by
HTNV.12 About 9,000−12,000 HFRS cases are reported in
China each year, with a CFR of approximately 1%. These cases are
distributed throughout China.13 In South Korea, about
400−600 cases of HFRS are reported annually, with a CFR
1%−2%.14
SEOV was first discovered in South Korea in 1982.15While SEOV mainly circulates in China and South Korea, it is the only
hantavirus that is globally distributed.16 This is
consistent with the global distribution of its hosts Norway rats
(Rattus Norvegicus ).17 SEOV infection accounts
for about 25% of HFRS cases worldwide, with a CFR less than
1%.3
DOBV was first discovered in Slovenia in 1992.18 It is
mainly distributed in Slovenia, Czech Republic, Poland, Russia, Serbia,
Greece, Germany, Denmark, France, and other European
countries.19 The pathogenicity of DOBV varies
according to its genotypes. The Dobrava and Sochi genotypes are highly
pathogenic, with a CFR of 10%−15%.20 The Kurkino
genotype is less virulent and causes only mild HFRS, with a CFR of
0.3%−0.9%. The Saaremaa genotype does not cause
mortality.19
PUUV was first discovered in Finland in 1980.21 PUUV
is mainly distributed in central, northern, and eastern European
countries.5 It caused more than 3000 HFRS cases each
year in Europe between 2010 and 2020. They are usually mild, with a CFR
of 0.1%−0.4%.3,5
ANDV was first discovered in Argentina in 1995.22 ANDV
is mainly distributed in Argentina and Chile and causes dozens of
HCPS/HPS cases annually with a CFR about 40%. ANDV can be transmitted
among humans.23
SNV was first detected in 1993 in the USA.24 SNV
circulates in the USA, Canada, and Mexico, and causes dozens of HCPS/HPS
cases annually with a CFR of 30%−35%.25,26
Other viruses in Orthohantavirus , such as Tula virus(TULV) in many Eurasia countries,27 Bayou virus(BAYV) in USA,28 Choclo virus (CHOV) in
Panama,29 and Laguna Negra virus (LANV) in
South America,30 have been identified as pathogenic to
humans.